Poster Liver

Portal hypertensive colopathy is a recently described entity in patients with or without liver cirrhosis. Its definition, prevalence, associated factors, colonic distribution, and clinical significance remain controversial. It is recognized as a potential cause of life-threatening lower intestinal bleeding. In contrast to upper gastrointestinal bleeding for varices, treatment for acute and long-term control of bleeding from portal hypertensive colopathy is not standardized. We report a case of a 32-year-old female who has portal hypertension secondary to chronic portal vein thrombosis, a complication of umbilical vein catheterization in infancy for the treatment of severe neonatal jaundice. She develops chronic and recurrent hematochezia with severe anemia requiring multiple admissions for transfusion and endoscopy. Radiological examinations show liver is not cirrhotic. Esophagogastroduodenoscopies reveal small non-bleeding gastroesophageal varices, and colonoscopies show multiple telangiectatic spots with rectal varix.

# 1344 Perceptions of non-alcoholic fatty liver disease-A community-based study Authors: HH SHIM [1]; GBB GOH [1,3]; C KWAN [1]; SY LIM [2]; NKK VENKATANARASIMHA [2], RA BAKAR [2]; DSM LAU [2]; TL KRISHNAMOORTHY [1]; KH TAY [2,3]; WC CHOW [1,3] Affiliations: [1]Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore [2]Department of Diagnostic Radiology, Singapore General Hospital, Singapore [3]Duke-NUS Graduate Medical School, Singapore Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and is associated with metabolic syndrome. Various epidemiological studies have reported prevalence rates between 5% and 30%. Local epidemiological data suggest an increasing prevalence of metabolic syndrome in Singapore. However, data on NAFLD are limited. We investigated the prevalence and local perceptions of NAFLD in Singapore. Methods: Attendees at a gastroenterology public forum were enrolled in a cross-sectional observational study, evaluating demographic, anthropometric, liver ultrasound, and clinical information. The diagnosis of NAFLD was based on sonographic criteria. Metabolic syndrome was defined according to International Diabetes Federation guidelines. Perceptions of NAFLD were explored using a self-administered questionnaire. Results: Two hundred and twenty-seven subjects were recruited with NAFLD diagnosed in 40% of the cohort. Subjects with NAFLD tended to be male (53.9% vs 33.9%, P = 0.007), are older (mean age 57.4 vs 51.9 years old, P = 0.012), had higher mean body mass index (BMI; 24.4 vs 21.6 kg/m 2 , P < 0.001), with larger waist circumferences (P = 0.01) and more often fulfilled criteria for metabolic syndrome(25% vs 11.4%, P = 0.014). Interestingly, subjects with NAFLD had a mean BMI (24.4 kg/m 2 ) that was within the non-obese range. The majority of subjects had heard of NAFLD, but they tended to underestimate their risk of having the disease. Receptiveness towards screening for NAFLD was positive. Conclusion: Our study suggests a significant local prevalence of NAFLD including non-obese individuals. Despite general awareness about NAFLD, they tended to underestimate their risk of having the disease. Better public education is needed to improve understanding.
# 1393 Usefulness of controlled attenuation parameter for quantifying hepatic fat content in patients with biopsy-proven non-alcoholic fatty liver disease Authors: N FUJIMORI [1]; N TANAKA [2]; E TANAKA [3] Affiliations: [1]Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan [2]Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Japan Background and Aim: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, [1][2][3] but its application to absolute hepatic fat quantitation remains unclear. The aim of this study was to examine whether CAP is correlated to real hepatic fat content in NAFLD patients. Methods: Fifty-nine NAFLD patients underwent percutaneous liver biopsy were enrolled. CAP was measured using FibroScan® just before liver biopsy. The percentage of fat droplet area to hepatocyte area in the biopsied specimen was determined morphometrically using a computerized optical image analyzing system. The correlation between CAP and liver histology was examined. Results: Controlled attenuation parameter showed an excellent correlation to actual liver fat percentage in the NAFLD patients having body mass index (BMI) < 28 kg/m 2 (r = 0.547, P < 0.001), especially < 25 kg/m 2 (r = 0.678, P = 0.001), but the meaningful correlation disappeared in patients with BMI > 28 kg/m 2 . In patients with BMI < 28 kg/m 2 , CAP quantitativeness was affected by the presence of fibrosis, but not hepatocyte ballooning and lobular inflammation. Conclusions: Controlled attenuation parameter may be a promising tool for quantifying hepatic fat content in NAFLD patients having no or mild obesity without liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients having BMI > 28 kg/m 2 or hepatic fibrosis.

References:
1 placebo group developed cirrhosis, while none of the patients in the silymarin group did. Conclusions: A significantly higher percentage of patients experienced NASH resolution and improvement in fibrosis stage after 48 weeks of treatment with silymarin compared with placebo.
(P < 0.05). Conclusions: We successfully constructed stably transfected BRL-3A and HSC-T6 cells with upregulation/downregulation of Nrf2. The oxidative stress model shows that Nrf2 has anti-oxidative stress ability in both cells, and this effect may be probably through the regulation expression of p66Shc and IQGAP1.
Introduction: Non-alcoholic fatty liver disease is associated with cardiovascular morbidity and mortality. Patients with chronic kidney disease (CKD) are in increased risk of cardiovascular deaths. Aim: This study aimed to investigate the presence of possible liver disease detected by functional liver tests and transient liver elastography (TE) in a group of the patients with different stages of chronic kidney disease (CKD). We investigated also whether the type of disorder end length of dialysis treatment in patients with CKD have any effect on steatosis and fibrosis grade, as documented by TE. Patients and Methods: Eighty patients with various stages of CKD were divided into subgroups in regard to etiology and duration of hemodialysis treatment. Liver stiffness was used to quantify liver fibrosis. Controlled attenuation parameter (CAP) was used to quantify liver steatosis. The device used was FibroScan (Echosens, Paris). The cut-off value for liver steatosis was 215 dB/m, and for the presence of fibrosis, it was a liver stiffness of > 7 kPa. Functional liver tests were measured for all patients. Results: No statistically significant correlations were detected between liver enzymes and CAP value. There was a statistically significant correlation detected between the value of liver enzymes and liver stiffness value (r = 0.231). We did not find statistically significant differences between etiology and duration of hemodialysis in regard to the functional liver test and CAP value. There was a statistically significant frequency of liver stiffness detected (P < 0.05,) in regard to etiology (with a higher frequency in autoimmune kidney disease). Conclusion: Transient live elastography provides the opportunity for non-invasive screening of non-alcoholic fatty liver disease in CKD patients. Keywords: liver steatosis, liver stiffness, transient elastography.
# 1774 Triglyceride regulation by leptin in alcoholic liver disease Authors: BALASUBRAMANIYAN V [1,2]; NALINI N [2] Affiliations: [1]Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India [2]Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, India Introduction: Alcohol-induced fatty liver disease is the most common and earliest response to the progression of fibrosis, cirrhosis, and/or hepatocellular carcinoma. The mechanism by which ethanol causes fatty liver disease is complex and not fully understood; however, augmented triglyceride (TG) accumulation in the hepatocyte is strongly associated with fatty liver and has been proposed as an important biochemical mechanism. We have previously noted that the potential beneficial effect of leptin on alcohol elicited toxicity in vitro. Objective: The purpose of this study was to evaluate the effect of leptin on ethanol-induced elevated hepatic TG synthesis and fatty acid composition in mice. Material and Methods: CD-1 mice (n = 10/group) were studied for 45 days. Four groups were studied: (i) control; (ii) leptin + control (230 μg/kg intraperitoneal every alternate day from day 30); (iii) alcohol (6.32 g/kg daily by gastric lavage, for 45 days); and (4) alcohol + leptin (as prior dosing). Results: Compared with naive mice, mice with ethanol supplementation had significantly (P < 0.05) increased plasma and hepatic TG levels and a key enzyme involved in TG synthesis such as acyl-CoA diacylglycerol acyltransferase (DGAT)2. Leptin administration to ethanol-treated mice shows significantly (P < 0.05) reduced hepatic and plasma TG concentrations and DGAT2 enzyme protein expression. Furthermore, ethanol supplementation significantly (P < 0.05) increased the percentage of palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and docosapentaenoic acid (22:5) levels, whereas Introduction: Recently, scientists have found that gut microbiota may play a role in the pathogenesis or progression of certain liver diseases, including alcoholic liver disease. Allicin is a pharmacologically active substance found in fresh aqueous extract of garlic, which has been found to have antimicrobial activity. The objectives of this study are to investigate the impact of allicin on the status of gut microbiota and its relationship with alcoholic fatty liver. Materials and Methods: The alcoholic fatty liver mouse experimental model was developed using male C57BL/6 mice that were fed an alcohol-containing liquid diet (Lieber-DeCarli diet). Allicin was administered orally everyday for 4 weeks in the treatment group. Results: The results indicated that allicin possesses potential hepatoprotective properties against alcoholic fatty liver by significantly reducing relative liver weight, fatty liver score, and the accumulation of triglycerides in the liver. Next-generation sequencing base-DNA sequencing results indicated that alcohol and allicin influence gut microbiota diversification in cecum. Allicin reduced positive correlation levels in some species of the cecum microbiota that related with alcohol intake, resulting in the increase of liver triglyceride level. In addition, the negative correlations were observed in control (36

Hepatocellular Carcinoma and Liver Tumors
Introduction: Dyskeratosis congenita is a disorder of poor telomere maintenance and is known to increase the risk of developing multiple types of malignancy, including epithelial cancers, particularly head and neck squamous cell carcinoma and gastrointestinal cancers. However, there are few reports of liver tumors arising in dyskeratosis congenita patients. We herein report the second case of hepatic angiosarcoma arising from dyskeratosis congenita. Case Description: A 23-year-old man was pointed out to have a liver tumor and subsequently consulted our hospital. He had a history of mental retardation. The patient was diagnosed with dyskeratosis congenita based on the following triad: (i) nail dystrophy; (ii) oral leukoplakia; and (3) abnormal skin pigmentation at 16 years of age. At 19 years of age, hepatosplenomegaly and liver dysfunction were noted. A hepatic tumor measuring 10 cm in diameter was detected on a routine checkup using abdominal ultrasound at 23 years of age. There was no history of alcohol consumption or smoking, and there was no reported exposure to Thorotrast, vinyl chloride, or arsenic. Hepatitis B surface antigens and HCV antibodies were negative, as were anti-nuclear antibodies and antimitochondrial antibodies. Abdominal computed tomography (CT) and magnetic resonance imaging revealed multiple hypervascular tumors, mainly in the hepatic right lobe. 18 F-Fluorodeoxyglucose positron emission tomography/CT showed increased uptake with a maximum standardized uptake value of 7.8 in the hepatic tumors and vertebral metastases. A needle liver biopsy disclosed atypical cell infiltration with spindle-shaped or oval-shaped nuclei, and immunohistochemistry showed positive results for vimentin, CD31, CD34, and blood coagulation factor VIII. The diagnosis based on the needle biopsy was epithelioid hemangioendothelioma or angiosarcoma. He died 4 months after the first detection of the hepatic tumor as a result of tumor progression and disseminated intravascular coagulation. An autopsy revealed a diagnosis of angiosarcoma with metastasis to the lung, left adrenal gland, spleen, and vertebrae.
# 1035 Tolvaptan for hepatocellular carcinoma patients with poor liver function Authors: TAKESHI ARAMAKI; EMIMA BEKKU; RUI SATO; MICHIHISA MORIGUCHI Affiliation: Shizuoka Cancer Center, Shizuoka, Japan Aims: The aim of this study is to evaluate the efficacy of tolvaptan for hepatocellular carcinoma (HCC) patients with poor liver function. Patients and Methods: Between Oct. 2013 and Feb. 2015, we evaluate 19 HCC patients with poor liver function treated using tolvaptan (female/male: 4/15, median age; 69 years old). Treatment dose is 7.5 mg/body in all patients. We evaluate the efficacy (disappearance of ascites/hydrothorax or weight loss over 5%), survivals, and toxicity. Results: We evaluated 19 patients. Child-Pugh was A/B/C = 1/14/4 patients. Mean Model for End-stage Liver Disease score was 11.45 (7.49-18.16) points. HCC stage was 0/I/II/III/IVa/ IVb = 1/0/2/8/5/3. Virus infection was HBV/HCV/HBV + HCV/non-HBV, non-HCV = 6/7/3/3. The mean follow-up period was 96.5 days. Tolvaptan was considered effective in 11 patients (57.9%) without major complications. The overall survival is 90 days, and median survival time of tolvaptan effective patient and non-effective patients is 167 and 87 days, respectively (P = 0.0673). Prothrombin time-international normalized ratio and serum K+ were pointed out as predictive factors of effect. Discussion: The treatment effect of tolvaptan appeared in 57.9% of patients who had HCC with poor liver function, and the predictive factor is prothrombin time-international normalized ratio and serum K+. However, this study includes only a small number of patients and is retrospective; therefore, a prospective study with a larger sample size is necessary to define the treatment effect and the predictive factor. Conclusion: Tolvaptan may be effective as palliative therapy for HCC patient.
analyzed. VEGF_1 was defined as pre-LDLT day 1, and VEGF_2 as post-LDLT day 1. VEGF_3 was divided into VEGF_3N, which is 1 month post-LDLT without HCC recurrence (n = 41), and VEGF_3P, which is the day of HCC recurrence (n = 9). The time to HCC recurrence was 90-1352 days.
Wilcoxon signed-rank test and mixed-model repeated-measure analysis were used to investigate. Results: The data profile was presented as Table 1. There was statistical significance only between VEGF_1 and VEGF_3N and between VEGF_1 and VEGF_2 (P = 0.022 and 0.012), but there was no significant difference between VEGF_2 and VEGF_3N, between VEGF_1 and VEGF_3P, between VEGF_2 and VEGF_3P, and between VEGF_3N and VEGF_3P (all were P > 0.05). Discussion: For both HCC recurrence and liver graft regeneration after LDLT, angiogenesis and the VEGF receptor pathways might be activated, possibly resulting in the loosening of intercellular junctions of endothelial cells and promoting angiogenesis. The VEGF receptor pathway plays a physiological role that may not differentiate between HCC recurrence and liver graft regeneration after LDLT. Liver graft regeneration requires significant blood flow and leads to the activation of this pathway. Conclusions: The implication of VEGF in case of LDLT should be that liver graft regeneration may play a major role in the clinical investigation.
# 1093 Malignant peripheral nerve sheath tumor of the liver Authors: NORIO HORIGUCHI [1,2]; SATORU KAKIZAKI [1]; TOSHIYUKI OTSUKA [1]; DAICHI TAKIZAWA [2]; YUICHI YAMAZAKI [1]; KEN SATO [1]; YOSHIHIRO OHNO [3]; MOTOYASU KUSANO [4]; MASANOBU YAMADA [1] Affiliations: [1]Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan [2]Department of Internal Medicine, Tone-Chuo Hospital, Numata, Gunma, Japan [3]Department of Pathology, Tone-Chuo Hospital, Numata, Gunma, Japan [4]Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Gunma, Japan Introduction: Malignant peripheral nerve sheath tumor (MPNST) of the liver is rare. Most cases of MPNST are accompanied by neurofibromatosis 1 (von Recklinghausen's disease). Materials and Methods: We herein report a case of a 72-year-old woman with MPNST without neurofibromatosis 1, which was diagnosed by an autopsy. In addition, we review the pertinent literature of MPNST of the liver. Results: The tumor occupied the entire lobe of the liver and was 18 cm in maximum diameter. The tumor revealed necrosis and cystic changes with hemorrhage and metastasized to the peritoneum. Microscopically, it was composed of pleomorphic spindle cells with hyperchromatic nuclei and mitogenic figures. The spindle cells stained positive for both S-100 and vimentin antibodies, which suggests this is an autopsy case of MPNST of the liver. Introduction: Sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC) at present, but it cannot be used in patients with liver cirrhosis (LC) nor thrombocytopenia. In our previous studies, it was revealed that LC can be reduced by an increment of platelets with administration of thrombopoietin (TPO). Eltrombopag (EP), TPO receptor agonists, has antitumor effects on several kinds of cancers in spite of lack of the TPO receptor. It is still unclear whether EP has an antitumor effect on HCC. The aim of this study was to clarify the antitumor effect of EP on HCC in vitro. Materials and Methods: To verify the antitumor effects of EP in vitro with HepG2, Hep3B, and Huh7, the assays were carried out for cell proliferation with WST8, DNA synthesis with BrdU, flow cytometry, and western blot. To clarify the antitumor mechanism of EP, iron preloading into HCC was performed and determined the effect of iron chelator deferoxamine. In addition, the combination effect of EP and sorafenib were investigated. Results: It was revealed that EP had a strong antitumor effect on HCC by suppression of cell cycle-related protein cyclin D1 and resulted in cell cycle arrest in the G0/G1 phase. Iron preloading into HCC cells resulted in an inhibition of the anti-proliferative effects of EP. Antitumor effect of EP did not compete with sorafenib. Conclusion: Our results suggest that EP would be a good candidate for chemotherapy of HCC in patients with LC and thrombocytopenia. Keywords: cell cycle, cirrhosis, eltrombopag, hepatocellular carcinoma, Huh7, iron chelate, thrombocytopenia, thrombopoietin, liver cancer, liver cirrhosis, sorafenib.
Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage D hepatocellular carcinoma (HCC) often have poor clinical outcomes. The purpose of this study was to compare the effect of active tumor treatment and supportive care for patients with BCLC stage D HCC. Methods: We conducted a retrospective study. There were a total of 138 patients who were diagnosed as BCLC stage D HCC at Taipei City Hospital Ren-Ai Branch from 1999 to 2013. The duration Background: Radiofrequency ablation (RFA) has played a key role in the management of small hepatocellular carcinoma (HCC) worldwide. We have performed laparoscopic RFA (LRA) using a multipolar RFA system (CelonPOWER System, Olympus Medical Systems, Japan) for treatment of HCCs since 2014. We assessed the efficacy and safety of multipolar LRA by short-term results. Methods: We performed LRA under general anesthesia in patients with HCCs ≤ 4 cm and ≤ 3 nodules. An RFA needle applicator was inserted under laparoscopic ultrasonography guidance, regardless of tumor location. It aimed at the parallel insertions based on "dosimetry table" and no-touch ablation as much as possible. Results and Discussion: Fifty-nine patients with 100 HCCs were treated by multipolar LRA. The maximum diameter of tumor averaged 22.7 ± 6.3 mm (10-42).
Operative time was 145 ± 40 min. The median follow-up time was 6.5 months (0.7-16.6). In all cases, sufficient ablated area as planned was obtained, and there was no procedural complication and local recurrence. The laparoscopic approach offers parallel insertion of multiple applicators without limitation by echo window and/or the ribs. Especially in case of HCC in hepatic surface, it is highly useful to avoid thermal injury to adjacent organs by maintaining the space with pneumoperitoneum and immersion ( Fig. 1). There was no local recurrence in the short-term results. To attempt at no-touch ablation may lead to obtainment of a sufficient safety margin. Conclusions: Although multipolar LRA required some proper skills, it is efficacious in treatment for localized HCCs by gaining a good ablated area safely. Background and Objectives: The FIB-4 index is a simple formula for predicting liver fibrosis. This study aimed to examine the relationship between the preoperative FIB-4 index and background liver fibrosis in nontumor regions of surgical specimens and investigate whether the FIB-4 index is a useful predictor in hepatocellular carcinoma (HCC) patients after curative resection. Methods: A total of 493 HCC patients treated with curative resection were retrospectively analyzed. We assessed the utility of the FIB-4 index as a predictor of advanced liver fibrosis (F4). The cut-off value for the FIB-4 index was determined using a receiver operating characteristic curve analysis, and the impact of the FIB-4 index on overall survival after surgery was evaluated. Results: F4 was found in 236 patients (47.9%). The FIB-4 index was significantly higher in the patients with F4 than in those with F0-F3 (P < 0.001). An FIB-4 index of 2.87 was the best cut-off point for predicting F4. In the multivariate analysis, the FIB-4 index was found to be an independent prognostic factor for overall survival after curative resection (hazard ratio: 1.71, 95% confidence interval: 1.18-2.47, P = 0.004). Additionally, elevated des-γcarboxyprothrombin (P = 0.011) and α-fetoprotein (P = 0.011) levels, the presence of microsatellite lesions (P = 0.014), and a serum albumin level lower than 40 g/L (P = 0.016)were also significant predictors of overall survival. Conclusions: The present study showed the FIB-4 index to be a predictor of background liver fibrosis and overall survival in patients treated with hepatectomy for HCC with curative intent. Background/Aims: Sorafenib, which is an orally administered target therapy, inhibits multiple protein kinases. At present, sorafenib is the only approved systemic therapy for patients with advanced stage (BCLC-C) HCC. Sorafenib combined with transarterial chemoembolization (TACE) is now more widely applied to treat unresectable HCC. The purpose of our study is to compare the overall survival of patients with HCC who were treated with sorafenib combined with TACE compared with sorafenib monotherapy. Methods: We collected baseline characteristics of HCC patients who ever received sorafenib treatment and were recruited from Ren-Ai Branch, Taipei City Hospital, during April 2010 to March 2014. Survival analysis was performed by the Kaplan-Meier method, and a comparison was made by log-rank test. Factors associated with survival rate were analyzed by Cox's regression analysis. Results: There were 106 patients (84 men and 22 women) who had ever received sorafenib treatment. The mean age was 65 ± 11.8 years (range, 38-90 years). Among them, 54 patients (50.9%) received sorafenib monotherapy, and 21 patients (19.8%) received combination therapy of sorafenib with TACE. There were no significant differences in terms of sex, age, tumor size, number of tumor, prevalence of HBV/HCV infection, child classification, and BCLC stage between patients treated with sorafenib alone and sorafenib + TACE. However, patients receiving sorafenib alone had a significantly higher ratio of αfetoprotein (AFP) > 400 ng/mL (60% vs 30%, P = 0.034) and shorter sorafenib treatment period (< 2 months sorafenib treatment, 70% vs 38%, P = 0.009). Patients receiving combination therapy of sorafenib with TACE had a significantly longer mean and median survival period compared with those receiving sorafenib alone (15.0 ± 3.4 and 10.9 ± 2.9 vs 5.2 ± 1.1 and 2.6 ± 0.6, respectively, P < 0.001). Multivariate Cox's regression analysis revealed that an AFP level of > 400 ng/mL (hazard ratio [HR]: 3.150, 95% confidence interval [CI]: 1.644-6.035, P = 0.001) and a sorafenib treatment period of < 2 month (HR: 3.966, 95% CI: 2.118-7.466, P < 0.001) were independent risk factors associated with poor prognosis. Conclusions: Our results indicated that survival rate is significantly longer in patients receiving sorafenib + TACE than in those with sorafenib alone. However, as most of our patients (88%) received sorafenib therapy for less than 6 months, the effect of sorafenib may be underestimated. Thus, further prospective randomized trials are required to confirm our findings.
# 1190 Translational study for liver carcinogenesis and developing personalized targeted treatment Authors: HP XIA [1,2]; KM HUI [2]; MH HU [1] Affiliations: [1]Department of Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, China [2]Division of Cellular and Molecular Research, National Cancer Center, Singapore Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of cancer-related death worldwide. Most of the liver cancer cases occur in 15 Asian countries. China has more than half of the newly diagnosed liver cancer cases in the world. Recurrence, metastasis, and chemoresistance are major obstacles to improving the prognosis of HCC. Methods: Combining gene expression profiles of HCC samples with or without early recurrence and established cell lines with epithelial or mesenchymal phenotype, some key factors like EDIL3 were identified as a novel regulator of epithelial-mesenchymal transition, which contributes to angiogenesis, metastasis, and recurrence of HCC. The expression of EDIL3 was evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemistry. The function of EDIL3 and targeted treatment strategies were investigated in liver cancer cells in vitro and orthotopic xenograft mouse model of HCC in vivo. Results and Discussion: EDIL3 induces epithelial-mesenchymal transition and promotes HCC migration, invasion, and angiogenesis in vitro. Mechanistically, overexpression of EDIL3, which was regulated by downregulation of miR-137 in HCC, triggered the activation of extracellular signal-regulated kinase (ERK) and transforming growth factor (TGF)-β signaling through interactions with αvβ3 integrin. Blocking ERK and TGF-β signaling overcomes EDIL3-induced angiogenesis and invasion. Using the orthotopic xenograft mouse model of HCC, we demonstrated that EDIL3 enhanced the tumorigenic, metastatic and angiogenesis potential of HCC in vivo. Conclusions: Therefore, it is promising for combating liver cancer through translation study and personalized therapy. EDIL3-mediated activation of TGF-β and ERK signaling could provide personalized therapeutic implications for HCC. Hepatocellular carcinoma (HCC) is a common disorder worldwide with a rising incidence in Egypt due to high prevalence of HBV-related and HCV-related chronic liver disease. α-Fetoprotein (AFP)-L3 and simplified HCC-α-fetoprotein routine test (HCC-ART) could help in early detection of HCC. However, their diagnostic accuracy was not previously compared among Egyptian patients. Aim: This study aimed to compare the diagnostic role of simplified HCC-ART and AFP-L3 in Egyptian patients with HCC. Methods: Serum levels of AFP and AFP-L3 were determined in 47 patients with HCC and 17 patients with liver cirrhosis admitted to Kasr Al-Aini Hospital-Cairo University. All HCC patients were diagnosed by the noninvasive criteria applied to cirrhotic patients according to 2012 EASL guidelines. AFP and AFP-L3 were assessed by the ELISA technique in all participants. AFP-L3% was defined as the percentage of AFP-L3 over the total AFP. A simplified HCC-ART was calculated (age [years] × log AFP × AAR [AST/ALT] × ALP/albumin [g/L]). The performance characteristics for the diagnosis of HCC were obtained using receiver operating characteristic (ROC) curves in study populations with a special emphasis on patients with 20 < AFP < 200 ng/mL. Results: All HCC patients had elevated AFP; 19 (40.4%) patients had AFP > 200 ng/mL, and 28 (59.6%) patients had an AFP of 20-200 ng/mL, while 15/17 (88.2%) non-HCC patients had AFP ≤ 200 ng/mL. Among the whole study population (n = 64), ROC yielded that the simplified HCC-ART and AFP at cut-off values of 634 and 62.5 ng/mL were able to diagnose HCC patients with higher sensitivity and specificity for HCC-ART (83% and 53%) compared with serum AFP (78.7% and 47%), respectively. Areas under the curve of AFP, simplified HCC-ART, and AFP-L3 were 0.7 (P < 0.05), 0.64 (P < 0.01), and 0.49 (P > 0.05), respectively, with a significant difference between AFP-L3 and simplified HCC-ART (P < 0.05). On the other hand, among the subset of patients with AFP ranging from 20 to 200 ng/mL (liver cirrhosis ± HCC, n = 43), areas under the curve of AFP-L3 and HCC-ART for HCC were 0.72 (P = 0.017) and 0.59 (P > 0.05), respectively. At a cutoff value of 10.9% for AFP-L3, HCC was diagnosed with 82% sensitivity and 67% specificity (Fig. 1). However, there was no significant difference between AFP-L3 and HCC-ART for HCC diagnosis among this subgroup. Conclusion: Simplified HCC-ART could be a helpful score in HCC diagnosis. AFP-L3 could improve the diagnostic performance particularly in patients with AFP below the diagnostic cut-off level for HCC, that is, 200 ng/mL. Background/Aims: Hepatocellular carcinoma (HCC) is a common primary liver cancer in Asia. Radiofrequency ablation (RFA) or surgical resection (SR) are both well-established treatments for early-stage HCC. However, the management of intermediate-stage or advanced-stage HCC was not well recognized. In this scenery, RFA is an alternative consideration. Material and Methods: In a single medical center, we carried out a retrospective study of patients with HCC meeting strict inclusion criteria who received RFA or SR from September 2009 to August 2013. Results and Discussion: In all, 37 and 120 patients with intermediate-stage to advanced-stage HCC who underwent RFA or SR were analyzed, respectively. The median size of HCC was 3.5 (range 1.7-5.8) cm for the RFA group and 7.1 (range 3.1-24) cm for the SR group. The average age of HCC diagnosis for each group was 62.1 ± 10.6 (range 43-79) years for RFA and 55.9 ± 12.4 (range 21-77) years for SR. The days of hospital stays were 6.5 ± 6.1 (range 3-37) days for RFA and 16.6 ± 12.7 (range 4-98) days for SR. The recurrence rate was 81.1% (30/37) for RFA groups but only 53.3% (64/120) for SR groups. Conclusion: For intermediate-stage to advanced-stage HCC, RFA could be applied to older patients and has short hospital stay but higher recurrence rate than the SR group. RFA may be considered as a safe and effective salvage treatment strategy for intermediate-stage to advancedstage HCC patients, especially those patients who have a high risk for SR. Further studies are needed to compare RFA and SR in patients with more-advanced-stage cancers. # 1227 Nucleos(t)ide analog therapy is associated with reduced hepatocellular carcinoma recurrence after radiofrequency ablation Authors: TENG-YU LEE [1]; JAW-TOWN LIN [2]; YI-SIOU ZENG [1]; YI-JU CHEN [3]; MING-SHIANG WU [4]; CHUN-YING WU [1,3] Affiliations: [1]Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan [2]School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan [3]Faculty of Medicine, School of Medicine, National Taipei,Taiwan [4]Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Efforts should be made to reduce the risk of tumor recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to investigate the association between nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence following RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004, andDecember 31, 2012, we screened 48 807 patients with newly diagnosed HBV-related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 patients who never used NA after RFA) who received RFA as a potentially curative treatment. Patients in the NAtreated cohort were randomly matched 1:2 with patients in the untreated cohort by age, gender, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 148 patients were recruited in the NA-treated group and 296 in the untreated group. The HCC recurrence rate of the NA-treated group was significantly lower than that of the untreated group (2-year recurrence rate: 43.0%, 95% confidence interval [CI]: 34.5-51.4% vs 55.2%, 95% CI: 49.2-61.1%; P < 0.01). In a modified Cox regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (hazard ratio 0.68, 95% CI: 0.50-0.92; P = 0.01). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in all patient subgroups. Conclusion: Nucleos(t)ide analog therapy was associated with a decreased risk of HCC recurrence among patients with HBV-related HCC following RFA.
# 1238 Ultrasound-guided biopsy of hepatic cystic lesions with a thick wall Authors: DY YANG; J QU*; H WANG; GQ SUI Affiliation: Department of Ultrasound, Third Hospital of Jilin University, Changchun, China Aims: This study aimed to assess the security and accuracy of US-guided biopsy of cystic lesions with a thick wall in liver. Methods: Fifteen patients with hepatic cystic masses were enrolled in this study from June 2012 to April 2015. We compared the pathology by US-guided biopsy with the postoperative. Patient selection included the following criteria: (i) the thickness of the cystic mass wall is more than 1 cm; (ii) the puncture path should be through normal hepatic tissues; and (iii) the thick wall of cystic masses should be parallel with the ultrasonic sound beam. In the process of US-guided biopsy, we performed the following: (i) detect the internal texture and adjacent tissue of the tumor in different sections; (ii) select those cyst walls that have a different blood supply to puncture; (iii) according to the direction of the cyst wall, select puncture site and approach; (iv) detect blood vessels in the tumor and peripheral blood vessels and bile duct; and (v) use color Doppler to detect whether there is bleeding. A coagulant was used in the cystic cavity to stop bleeding. Results: (i) US-guided biopsy of liver was performed in 15 patients successfully. (ii) The bleeding of one patient was stopped by using a coagulant in the cystic cavity. (iii) There was no serious complications after the implantation in other patients. (iv) The pathological results of US-guided biopsy agreed with postoperative pathologic results. Conclusion: (i) US-guided biopsy is less invasive, safe, and effective for tumor, especially for cystic tumor. (ii) Complications after US-guided biopsy can be treated in time. *corresponding author Correction added on 5 December 2015, after Online publication. Corresponding author is J QU.
# 1255 Assessment of percutaneous radiofrequency ablation treatment with Soloist and LeVeen needles for hepatocellular carcinoma patients Authors: HANG DAO [1,2]; LONG DAO [1,2] Affiliations: [1]Internal Medicine Department, Hanoi Medical University, Hanoi, Vietnam [2]Gastroenterology Department, Bach Mai Hospital, Hanoi, Vietnam Introduction: Hepatocellular carcinoma (HCC) is a common disease in the world as well as in Vietnam. Radiofrequency ablation (RFA) is a local therapy to destroy tumor tissue by heat. Materials and Methods: This is an interventional longitudinal study on HCC patients having ≤ 3 tumors with each tumor being ≤ 3 cm in size or with a single tumor of up to 5 cm and having Child Pugh A or B. The study was conducted in the Gastroenterology Department of Bach Mai Hospital from November 2011 to April 2015. Results: One hundred and twenty-seven patients with a mean age of 58.1 ± 10.3 underwent 368 times of RFA with the mean ablation times being 2.9 ± 1.5 in which 81 were treated only by RFA and 46 patients were treated by RFA combined with transarterial chemoembolization. HBV was the predominant cause of HCC with a rate of 67.7%. Eight patients underwent artificial ascites with a mean volume of 2125 ± 231 mL of 5% glucose, and two patients underwent artificial pleural effusion with a mean volume of 1100 ± 141 mL of 5% glucose due to difficult locations. The procedure was safe with the complication rate being 1.1% including hemothorax, ascites, pleural effusion, and hypervagal reaction, which were treated well by internal medicine. Fever and abdominal pain were recorded in 13.6% ablation times. After 1 month of the first RFA, 117 patients had complete and partial responses according to modified Response Evaluation Criteria in Solid Tumors (92.1%); after 9 months, 105 patients had complete and partial responses (82.7%). Forty-nine patients (38.6%) had better clinical response with gain weight and less fatigue. During follow-up time (18.1 ± 7.5 months), 5 patients died ( Background and Aims: Hepatocellular carcinoma (HCC) is a highly vascularized tumor with intense angiogenesis, but the molecular mechanisms regulating angiogenesis have not been fully understood. We clarified the relation of CD105 expression with HCC and explored its importance with HCC prognosis comprehensively. Methods: A total of 112 hepatocellular carcinoma patients were analyzed. Immunohistochemical staining for the CD105 was performed in tumor and non-tumor specimens. We further compared the relation of CD105 with clinicopathological parameters by immunohistochemical staining. We also analyzed 30 pairs of fresh tissue specimens including a tumor part and a non-tumor part in 30 hepatocellular carcinoma patients using the quantitative real-time polymerase chain reaction and western blot and analyzed the expression of endoglin with clinicopathological parameters. Results: We demonstrated that CD105 was more abundant in the non-tumor part of liver in HCC patients. And the well-differentiated HCC and early-stage HCC and lower serum α-fetoprotein level had higher microvessel density of CD105 expression. And a higher CD105 expression had a lower tumor recurrent rate after operation. In western blot, the early-stage and smaller HCCs had a higher CD 105 expression. The quantitative real-time polymerase chain reaction also showed a higher CD 105 expression in the non-tumor part than in the tumor part. Conclusions: CD105 has an important role in HCC angiogenesis, and this study provides evidence for HCC prognosis related with CD105 expression. We obtained similar results and validated them by immunohistochemical staining and quantitative real-time polymerase chain reaction and western blot. Introduction: An estimated 695 900 liver cancer deaths occurred worldwide in 2008. Based on US statistics, the 5-year survival rate is only 15%. The low survival rate is attributable to concomitant liver cirrhosis, which in itself is fatal. Case Description: We present a case of a 65year-old lady who survived a decade despite being diagnosed with liver cancer in a cirrhotic liver. She had chronic hepatitis C infection but achieved sustained viral response following therapy with pegylated interferon and ribavirin in 2005. A year later, she was diagnosed with liver cancer during surveillance. The cancer measured 2.2 × 2.6 × 1.7 cm in segment 2. Surgery was not an option because of her poor liver reserve. She was not keen on further treatment and opted for conservative therapy. A repeated computed tomography scan after 5 years revealed the tumour had doubled in size to 4.2 × 5.8 × 4.2 cm with other new lesions. Regular monitoring of α-fetoprotein showed a steady rise from the initial hundreds to thousands and finally > 10 000 ng/mL. She remained asymptomatic until her 10th year when she started experiencing liver decompensation. Despite a known poor survival outcome, she defied all odds to live a decade with a European Cooperative Oncology Group score of 1 despite no cancer treatment. Conclusion: Liver cancer is highly heterogeneous, and cancer genomics may hold the key to explaining the aggressiveness and indolence of certain cancer subtypes. By unlocking this, we may one day individualize liver cancer treatment. Some may not require aggressive treatment regimes where the benefits and risks need to be weighed against survival prognosis. Objective: Elevated plasma fibrinogen (FBG) level is associated with tumor progression and poor patient outcomes in several cancers. However, the prognostic value of FBG in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is unclear. The aim of this study was to investigate the prognostic value of preoperative plasma FBG level in HCC patients after LT and build a scoring model based on FBG for predicting tumor recurrence after LT. To our knowledge, this is the first report discussing the prognostic value of preoperative plasma FBG level in HCC patients after LT. Methods: We analyzed the outcome of 99 patients who underwent LT for HCC at our institution. Clinical and pathological factors were evaluated by Kaplan-Meier analysis, and survival curves were compared using the log-rank test. Cox multiple-regression analysis was performed to determine the parameters predicting HCC recurrence and patient survival. The optimal cut-off value for elevated level of preoperative FBG was determined by using a receiver operating characteristic curve analysis. A scoring model was built by giving a value of 0 or 1 to independent risk factors selected by Cox regression analysis. Results: Preoperative FBG levels were significantly higher in patients with tumor recurrence (3.27 g/L) compared with those in patients without recurrence (2.34 g/L) (P < 0.001). A cut-off value for elevated FBG level of 2.68 g/L was defined using receiver operating characteristic curve analysis. There were significant differences in disease-free survival between the elevated FBG group and normal FBG group (78.4% vs 37.2%, P = 0.001). Patients with macrovascular invasion and α-fetoprotein > 400 ng/mL also had significantly higher preoperative plasma FBG concentration than the others. Macrovascular invasion, tumor number > 3, and FBG ≥ 2.68 g/L were independent risk factors of HCC recurrence after LT. A scoring model was built to predict the risk of tumor recurrence, with a sensitivity of 68.3% and a specificity of 87.5%. Conclusion: Pretransplant elevated plasma FBG level significantly increases the risk of tumor recurrence in patients after LT for HCC. The scoring model we built based on FBG level and tumor number strongly correlates to tumor recurrence and may aid in the selection of patients that would most benefit from transplantation for HCC.

References
# 1385 Prognostic factors of transarterial chemoembolization/transarterial embolization for hepatocellular carcinoma patients with prolonged survival of more than 3 years Authors: G SARVESH [1,2]; CM JENG [3,4]; WM TSAI [5]; YW HUANG [1,[6][7][8]; JT HU [1,4]; SS YANG [1,4]  Aims: This study aimed to investigate the expression of β-arrestin 1 and its possible function in the course of non-alcoholic fatty liver disease (NAFLD) progressing to hepatocellular carcinoma. Materials and Methods: C57BL/6 mice were fed with chow diet and high-fat diet (HFD) for 9, 24, and 48 weeks, and the incidence of hepatocellular carcinoma was observed at the end of 48 weeks. Expressions of β-arrestin 1 in the liver tissue of mice were detected by western blot and real-time reverse transcription-polymerase chain reaction. Results: The liver of mice exhibited the typical appearance of fatty liver after 9 weeks of HFD. At the 48th week or the end-point of study, the incidence of hepatocellular carcinoma was 0/23 in the chow diet group and 4/22 in the HFD group with a statistically significant difference (P < 0.05). Compared with the chow diet group, the HFD group had statistically increased β-arrestin 1 protein expression of liver tissue at 9 weeks (P < 0.05), and the level of β-arrestin 1 protein was positively correlated to the duration of HFD (r = 0.949, P = 0.000). Furthermore, the expressions of βarrestin 1 protein in tumor tissue was dramatically higher than that of fatty liver tissue from the same period of HFD (P < 0.05). The change of β-arrestin 1 mRNA exhibited the same tendency. The order from lowest to highest in mRNA level of β-arrestin 1 was liver tissue from mice fed with chow diet for 9 weeks, liver tissue from mice fed with HFD for 9, 24, and 48 weeks, and tumor tissue from hepatocellular carcinoma (all P < 0.05). Conclusions: It is easy to develop NAFLD in mice fed with HFD, and there is a higher incidence of hepatocellular carcinoma in NAFLD mice. β-Arrestin 1 might play an important role in the course of NAFLD progressing to hepatocellular carcinoma. Keywords: β-Arrestin 1; hepatocellular carcinoma; non-alcoholic fatty liver disease (NAFLD).
# 1533 Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new-onset diabetes: A nationwide cohort study Authors: YW HUANG [1][2][3]; TC WANG [4]; SC FU [1]; JT HU [1,5]; DS CHEN [3,[6][7][8]; SS YANG [1,5] 6.9 (3.8-11.3) months; less than 20% of patients stopped the treatment during the first month. By applying the score, there were subgroups of different prognoses, and the score's variation was correlated to survival. The NIACE score with a threshold value < 3 corresponded to two groups with different median overall survival into the three external cohorts: Nancy, NIACE < 3 (n = 28), 16 (14-25) months versus NIACE ≥ 3 (n = 55), 6 (4-8) months, P < 0.0001; Rennes, NIACE < 3 (n = 37), 10.6 (4.1-17.1) months versus NIACE ≥ 3 (n = 46), 5.1 (2.9-7.4) months, P < 0.0001; and Bordeaux, NIACE < 3 (n = 44), 11.3 (8. 1-15.9) months versus NIACE ≥ 3 (n = 75), 6.0 (4.3-7.6) months, P < 0.0001. The median duration of sorafenib administration in the four cohorts varied from 2.2 (0.7-4.1) months to 4.2 (2.6-7.1) for patients with a NIACE score > 3 versus 6.0 (3.9-13.1) months to 9.9 (6.8-21.5) months for patients with a NIACE score < 3. Background and Aims: The annual mortality rate by chronic liver diseases and hepatocellular carcinoma (HCC) that are associated with hepatitis B and C has been shown to be reduced by antiviral treatments. However, the prolonged life expectancy of patients with chronic viral hepatitis may increase the cumulative incidence of and mortality by HCC. Methods: Data on incidence rates of HCC were obtained from the Korea Central Cancer Registry, which compiles nationwide data on all newly diagnosed cancers. Data on cause-specific mortality and on liver transplantation were obtained from the Korean National Death Registry (Statistics Korea) and Korea National Organ Sharing, respectively. Results: The mean age at death by liver diseases and HCC significantly increased between 1998 and 2013 (56.3 vs 64.8 years; β = 0.65, P < 0.001, and 60.0 vs 63.9 years; β = 0.30, P < 0.001, respectively). Between 1998 and 2013, the mortality rate by liver diseases and viral hepatitis significantly decreased (25.4/100 000 people vs 14.7/100 000 people; β = À0.77, P < 0.001). The incidence rate of and mortality rate by HCC significantly increased during the same period (28.2/100 000 people vs 32.9/100 000 people; β = 0.45, P < 0.001, and 20.0/100 000 people vs 22.6/100 000 people; β = 0.11, P = 0.01). The trends in mortality rates by liver diseases and HCC were consistently observed after adjusting for liver transplantation and mortality by alcoholic disease.  1, 9.2 ± 9.7 months, P < 0.0001). External cohort was made of 144 BCLC A, B, and C HCC patients; the mean OS was 51.6 ± 3.9 months. By Applying a NIACE ≤ 1 threshold, the mean OS of the NIACE ≤ 1 group was 66 ± 6 versus 41 ± 5 months for the NIACE > 1 group, P < 0.0001. The score also distinguished between two BCLC B HCC patient populations having significantly different median OS: 50 (27-78) versus 16 (9-36) months, P = 0.0002. Conclusion: There was a significant difference survival between patients having a low score, which include not only BCLC A HCC but also BCLC B HCC, and the others patients. Without referring to the stage of the disease, survival is probably influenced by the infiltrating nature of the tumor and a significantly high AFP level. NIACE is a simple score, which is able to distinguish between subgroups with different prognoses, within an HCC population treated by surgery.
# 1688 Hepatectomy for malignancy confined to segment VII Author: CHIAH YANG CHAI [1]; CHEN CHIA CHE [2]; LI HUNG CHAI [3]; CHOU CHIA CHENG [3]; HSIEH YEI SAM [3]; LIN MING HUI [3]; HUANG CHIA HSUN [3]; HSU KUEI [3] Affiliations: [1]Tao Yuan General Hospital, Taoyuan, Taiwan [2]Taipei Medical University Hospital, Taipei, Taiwan [3]Taoyuan General Hospital , Ministry of Health and Welfare, Taoyuan, Taiwan Introduction: Despite advancement in surgical technique, resection of hepatic malignancy located in Couinaud's segment VII remains challenging because of its deep location. Full mobilization of the right liver is necessary to facilitate resection. The most common surgical procedure for HCC is posterior sectionectomy and wedge resection for metastasis. Material and Method: Between August 2008 and March 2015, 127 consecutive patients received hepatectomy for HCC, metastasis, cholangiocarcinoma, and others. Twenty-seven patients received hepatectomy for malignancy confined to segment VII. The operation procedure selected was based on background liver function, tumor size, and tumor number. Result: Fifteen patients with HCC received posterior sectionectomy, and two patients with huge HCC had right hepatectomy. The remaining 10 patients with metastasis received either wedge resection or posterior sectionectomy. Conclusion: For malignancy located in segment VII, full mobilization of the right liver is essential for safe hepatectomy. The procedure may range from wedge resection, posterior sectionectomy to right hepatectomy depending upon the background liver function. Keywords: hepatectomy, posterior sectionectomy, segment VII.
# 1690 The effect of confluent hepatic fibrosis on hepatectomy Author: LI HUNG CHAI [1]; CHEN CHIA CHE [2]; CHIAH YANG CHAI [3]; CHOU CHIA CHENG [1]; WANG CHI CHAO [1]; CHENG SHENG FANG [1]; LAI CHUN YING [1]; CHEN CHI FENG [1]; LIU CHENG HUNG [1] Affiliations: [1]Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan [2]Taipei Medical University Hospital, Taipei, Taiwan [3]Tao Yuan General Hospital, Taoyuan, Taiwan Introduction: Confluent hepatic fibrosis (CHF) is a mass-like fibrosis seen in some patients with advanced fibrosis. The morphological changes were attributed to selective volume reduction, especially middle hepatic venous (MHV) drainage area. The long length of MHV with its relatively large drainage area may account for the selective volume reduction. The topographical change in the surface anatomy of such liver may cause confusion in major hepatectomy. # 1752 Unusual presentation of metastatic thymic carcinoma in liver: A case report Authors: HAO-WEN DAI [1]; CHING-WEI CHANG [1][2][3][4]; CHIA-HSIEN WU [5]; CHIA-YUAN LIU [1][2][3][4]; MING-JEN CHEN [1][2][3]; TSANG-EN WANG [1][2][3]; CHENG-HSIN CHU [1][2][3]; SHOU-CHUAN SHIH [1][2][3]; CHIA-CHI TSAI [6];   one-third in all cases. The clinical outcome for advanced stage of thymic carcinoma depends on complete resection. However, complete surgical resection is not always possible in cases of advanced-stage thymic carcinoma because of local regional invasion. We reported a 61-year-old man who had a medical history of neurofibroma involving the thoracolumbar spine and underwent resection because of paraplegia in 2008 and 2010. One hepatic mass was found accidentally by abdominal ultrasound on November 2014. On abdominal ultrasonography, this huge mass was homogeneous hyperechogenicity (Fig. 1). Computed tomography (CT) of the abdomen (Fig. 2) presented that this metastatic mass had soft tissue density with central calcification. Fluorodeoxyglucose (FDG) positron emission tomography was performed to search for the primary site of malignancy, and lobulated FDG hypermetabolic lesions were located in the anterior mediastinum (Fig. 3). Chest CT presented a lobulated soft tissue density mass with central necrosis, and perifocal lymphadenopathy occupied anterior mediastinum. The patient underwent resection of the thymic tumor followed by curative partial hepatectomy. It was proved to be thymic basaloid carcinoma with liver metastasis (Fig. 4). After surgical intervention, he received concomitant chemoradiotherapy 1 month later. The patient was still alive 6 months after the appearance of the liver metastasis.   Background: The enhanced liver fibrosis (ELF) test is based on three extracellular matrix markers associated with liver fibrosis: hyaluronic acid, tissue inhibitor of metalloproteinase-1, and propeptide of type III procollagen. While epidemiologic studies suggest that the ELF score can predict transplant-free survival in patients with cirrhosis, the use of ELF score as a predictor of hepatocellular carcinoma (HCC) has not been examined. Methods: We examined the association between ELF scores and HCC risk using a matched case-control set of 61 cases and 61 controls nested within the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45-74 years), who were recruited during 1993-1998 in Singapore. Blood from cases was collected before cancer diagnosis, and controls were matched by age, gender, and time of blood taking. Results: Hepatocellular carcinoma cases had significantly higher serum levels of hyaluronic acid, tissue inhibitor of metalloproteinase-1, propeptide of type III procollagen, and ELF scores than controls (all P < 0.001). An optimal cut-off of 10.2 for ELF score distinguished between cases and controls with an area under the receiver operating characteristic curve of 0.82 (95% confidence interval, 0.75-0.90) and with a sensitivity of 72% and a specificity of 80%. Compared with lower scores, an ELF score of 10.2 or above was associated with a 26-fold increase in risk of HCC (odds ratio [OR] = 25.75, P = 0.002). The risk estimate was much higher among individuals negative for serology markers (b) Microscopically, the liver parenchyma shows infiltration of basaloid tumor cells with high nuclear cytoplasmic ratio and occasional mitotic figures, consistent with metastatic thymic carcinoma of liver (hematoxylin-and-eosin stain, magnification 40×).
(a) there was prominent palisading of the tumor cells around the neoplastic islands and nests. The sections reveal a malignant tumor composed of ovoid to short-spindle neoplastic cells with a high nuclear cytoplasmic ratio and frequent mitoses arranged in cystic or solid patterns from surgical specimen of thymus (hematoxylin-andeosin stain, magnification 100×).
of chronic infection with HBV or HCV (OR = 27.75, P = 0.002) than among those who were positive (OR = 3.94, P = 0.23). Conclusion: Our data demonstrated that the ELF score is a potent predictive marker of non-viral hepatitis-related HCC, potentially allowing for personalized treatment and surveillance.
# 1788 Androgen receptor expression decreases recurrence of hepatocellular carcinoma after liver resection Authors: HSUEH-CHOU LAI [1,2]; CHUN-CHIEH YEH [1,2]; LONG-BIN JENG [1]; SHANG-FEN HUANG [1]; PEI-YING LIAO [2]; FU-JU LEI [2]; CHENG-LUNG HSU [3]; XIUJUN CAI [4]; CHAWNSHANG CHANG [2,4,5]; WEN-LUNG MA [1,2] Affiliations: [1] # 1811 MicroRNA-200a/b influenced curcumin therapeutic effects in hepatocellular carcinoma cells Authors: HUNG-HUA LIANG [1][2][3][4]; PO-LI WEI [1][2][3][4]; WEU WANG [2][3][4]; MING-TE HUANG [2][3][4]; YU-JIA CHANG [1,2,4] Affiliations: [1] ). The expression patterns of miR-200 family members were assessed with real-time polymerase chain reaction. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibiotics. The anticancer effects of curcumin on J5-200a, J5-200b, and J5 control cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry cell cycle analysis, and TUNEL assay. Results: We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR-200a/b. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5 control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad and found a decrease of Bcl-2 levels and increase of Bad levels in the J5 control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells. Conclusions: In this study, we dissected the role of the miR-200 family of miRNAs in the antitumor effects of curcumin on HCC. The findings from this investigation may provide important novel and potentially therapeutic insight into the application of curcumin for the treatment of liver cancer. The primary outcome variable was the successful completion of procedure. Secondary outcome variables were sedation-related adverse events during and immediately after procedure. Results: There were 113 elderly patients who underwent RFA procedure by using propofol-based deep sedation during the study period. Of these, 69 patients were in group A, and 44 patients were in group B. There were no significant differences in age, gender, weight, duration of procedure, and mean dose of propofol, fentanyl, and midazolam between the two groups. All procedures in both groups were successfully completed. Overall and cardiorespiratory adverse events in both groups were not significantly different. All adverse events were easily treated, with no adverse sequelae. Conclusion: Propofol-based deep sedation for percutaneous RFA in sick elderly patients by trained anesthetic personnel with appropriate monitoring was safe and effective. The clinical efficacy of this technique in sick elderly patients was not different or worse than in nonsick elderly patients. Serious adverse events were rare.
Reference: , and HBV genotype were also performed in these patients. We studied genotypes A-F in our study by the polymerase chain reaction method. Results: Mean age of presentation was 56.17 ± 11.65 years.
Male-to-female ratio was 13:1. Abdominal pain (79.3%), anorexia (62.1%), and weight loss(55.2%) were the most common symptoms, while ascites (72.4%), splenomegaly (51.7%), and hepatomegaly (41.4%) were the most common signs in these patients. Cirrhosis was present in 86.2% patients. Risk factors associated with HCC include smoking and alcohol consumption, which were present in 37.9% and 17.2%, respectively. Approximately half of patients had Child C liver cirrhosis. Occult HBV infection was present in 17.2%, and AFP levels above diagnostic range (≥ 400 ng/mL) were present in 51.7% patients. Hypoglycemia was noted in four patients. Multifocal HCC was present in 58.6% patients. Portal vein thrombosis and metastases were seen in 31% and 37.9% patients, respectively. One-year mortality was 79.3%. Single genotypes were present in 66.5%, and the rest had mixed genotypes. Genotype D (37.9%) was most common followed by genotypes B + D (27.6%).Genotypes A and A mix (A + D) and genotypes D and D mix (A + D and B + D) had reduced mortality as compared with other genotypes (genotype A + A mix, P = 0.017; genotype D + D mix, P = 0.034). Conclusion: Hepatitis B virus-related HCC was most commonly seen in the fifth decade of life, predominantly affecting male patients with underlying cirrhosis. Genotype B + D was noticed for the first time in the Indian subcontinent in these patients. These findings will have therapeutic and prognostic implications among these patients. 1537.97 ± 660.62 pg/mL in patients with BCLC stage D. One-way ANOVA showed P < 0.001 between mean serum VEGF levels and the severity in all BCLC stages. Post-hoc Tukey-Schaffe test showed significant statistical difference between BCLC stages A and C (P < 0.05), BCLC stages A and D (P < 0.001), BCLC stages B and D (P < 0.001), and BCLC Stages C and D (P < 0.001). There were no significant statistical differences between patients with BCLC stages A and B and between BCLC stages B and C. Discussion: VEGF serum was said to be correlated to the severity of HCC, and high levels were usually found in patients with vascular invasion or metastasis, thus indicating a poor prognosis in patients with HCC. Therefore, VEGF has the potential to assist in predicting tumor differentiation and vascular invasion. Background: Acetaldehyde is a major cause of alcohol hangover symptoms and may exert pivotal roles in developing cirrhosis and hepatocellular carcinoma from chronic alcoholic liver disease. This cytotoxic aldehyde is primarily metabolized by aldehyde dehydrogenase. Recently, a variety of anti-hangover products are commercially available; however, almost none of them has been proven to show enhanced activity of aldehyde dehydrogenase in a live subject. We aimed to investigate a specific product of interest. Methods: The enzyme activities of the anti-hangover candy were examined by in vitro and in vivo experiments to measure the amount of NADH formation which is generated through catalytic conversion of alcohol and acetaldehyde. A powder sample of a commercial anti-hangover product (KISLip®, PICO Entech, South Korea) was used as the experimental substance. In vivo examination tested the ethanol and acetaldehyde concentration in blood of rats with oral infusion of experimental substance Figure 1 Time-dependent change of acetaldehyde concentration in rat's blood for the case of anti-hangover substance 220 mg/kg orally given after 1 hour of ethanol intake.
before or after ethanol intake. Results: In vitro measurements of the activities of alcohol dehydrogenase and aldehyde dehydrogenase within the anti-hangover substance were 1.84 and 0.28 unit/g, respectively. The enzyme activities in experimental rats were significantly increased after substance gavages. Particularly, the cases with an oral intake of substance 220 mg/kg after 1 h of ethanol intake have shown more meaningful and obvious decreases in acetaldehyde concentration in blood ( Fig. 1).
Conclusions: Oral intake of anti-hangover substance (KISLip®) has significantly enhanced aldehyde dehydrogenase activity within rat circulation.
Further research on animal model of alcoholic liver disease using this substance is recommended.
# 1952 Transcatheter arterial chemoembolization with hydrophilic microsphere-A porcine study Authors: JUI-WEN KANG [1]; CHEN-HSI CHOU [2]; YI-SHENG LIU [3]; HONG-MING TSAI [3]; HUNG-WEN TSAI [4]; YU-JU CHEN [5]; MUH-RONG WANG [6]; Transcatheter arterial chemoembolization is the most commonly used treatment modality for these patients. We develop the microspheres to improve treatment response. Methods: We used pharmaceutical excipients that were generally regarded as safe or could be used as implants in humans to make emulsions. A two-flow method with modification was applied to produce microspheres. The sizes of our microspheres were adjustable by a sieving method, ranging from 100 to 750 μm based on clinical needs. The hydrophilic microspheres were loaded with doxorubicin. Under anesthesia, the piglets were embolized with hydrophilic microsphere via left/right hepatic and splenic artery by interventional radiologists. Serial blood tests and CT scan were performed to evaluate its efficacy and safety. All piglets were sacrificed 35 days later to obtain embolized liver and spleen tissue for histological examination. Results and Discussion: Ten piglets were treated with novel microsphere loaded with doxorubicin. After sacrifice, we can see significant embolization effects in embolized liver and spleen. The drug levels are not detected in blood, but in the embolized liver and spleen parenchyma. Significant degradation of the microsphere and tissue necrosis can be observed in pathological examinations. Transient elevation of WBC, GOT, and GPT were noted at 24 h after embolization. In addition, our microspheres are radiopaque and biodegradable. Conclusion: Transcatheter arterial embolization with novel microspheres loaded with doxorubicin is safe and effective in porcine study. Further clinical trial is needed to evaluate its safety and efficacy in clinical application.
# 1954 Hepatic actinomycosis mimicking a neoplasm-Case report Authors: DPCKA LAL, S SIVAGANESH Affiliation: University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka Introduction: Actinomycosis is a rare bacterial infection that manifests as acute on chronic inflammation with suppuration. Actinomyces Israeli is the commonest species isolated and found as a commensal in gastrointestinal and female genital tracts. Diagnosis of deep-seated actinomycotic abscess is difficult as it mimics neoplasms in imaging. Antibiotic of choice is conventional penicillin, and 4-6 weeks' parenteral followed by 6 months' oral treatment is recommended to prevent recurrence. Case Report: A 42-yearold otherwise healthy person presented with abdominal pain and fever for 10 days' duration. Examination revealed an acute abdomen and evidence of sepsis. Hematological and biochemical investigations were in favor of an acute inflammatory condition due to a pyogenic infection. Radiological evaluation was suspicious of a hepatic neoplasm or an abscess ( Fig. 1). Aspirate of the cystic areas of the lesion was negative for an infective etiology, but biopsy of solid areas showed histopathological evidence of actinomycosis ( Fig. 2). Patient was started on benzyl penicillin and then converted to coamoxiclave and clindamycin (based on microbiology opinion) due to practical problems of long-term parenteral penicillin therapy. The patient was treated intravenously for 2 weeks and discharged on oral antibiotics for 4 weeks. Repeat imaging was planned in 1 month, but patient was lost to follow up. Discussion and Conclusion: Hepatic actinomycosis should be considered an important differential diagnosis in patients with features of sepsis and evidence of hepatic neoplasm in imaging. Surgical interventions are not indicated if the patient is not deteriorating but should be followed up with imaging to exclude concomitant neoplasm.

References:
1  Background/Aims: Although sorafenib is the standard therapy for advanced hepatocellular carcinoma (HCC), the treatments vary in these patients. Accordingly, we evaluated the effect of different treatment strategies on overall survival (OS) in HCC cases. Methods: A retrospective study of advanced HCC patients receiving sorafenib was conducted. The primary outcome was the OS. Prognostic factors were assessed using Cox multivariate analysis. Results and Discussion: A total of 658 patients (mean age 54.4 years, 83.5% male) were analyzed; 275 were treated with sorafenib monotherapy, 20 with sorafenib followed by transarterial chemoembolization (TACE), 126 with a combination of the two, and 237 with TACE followed by sorafenib. The baseline characteristics of these groups were comparable. However, patients treated with combination therapy had more portal vein invasion (52.3%, P < 0.001). The sorafenib treatment duration was shorter in the TACE followed by the sorafenib group (81.9 days, P = 0.004). The median OS was comparable (11.3 months for sorafenib monotherapy, 19.3 months for sorafenib followed by TACE, 16.2 months for the combination, and 13.5 months for TACE followed by sorafenib; P = 0.22). However, in subgroup analysis of portal vein invasion cases, the combination (25.7 months, P < 0.001) and TACE followed by sorafenib (14.0 months, P = 0.011) treatments were associated with better OS than sorafenib monotherapy ( (Fig. 1). Elevated levels of GOT and GPT without jaundice or coagulopathy were found. An elevated level of AFP (13.85 ng/mL, normal range: < 8.78 ng/mL) was also found. HCC with BCLC stage C was diagnosed, sorafenib (400 mg twice daily) and entecavir (0.5 mg/day) were prescribed. Results: The levels of AFP, AST, and ALT were significantly reduced after 2 months of treatment with sorafenib. Her DNA level was also undetectable. The CT scan of the liver revealed a significant reduction of tumor size of more than 51.1% ( Fig. 2) (RECIST defined as partial response). The dosage of sorafenib was reduced to 400 mg/day due to hand-foot syndrome and skin reactions after 4 months of treatment. This patient has survived for more than 8 months after oral sorafenib administration till now.  Background and Study Aims: The poor prognosis of hepatocellular carcinoma (HCC) is due to high recurrence rate mainly caused by intrahepatic or extrahepatic metastasis. Paxillin, the most important adaptors in focal adhesion, is known to play an essential role in mediating the signal pathway for HCC progression. Within the paxillin superfamily, hydrogen peroxide inducible clone  is the most homologous to paxillin. Moreover, both adaptors play distinct but complementary roles in tumor progression of breast cancer. Our previous clinical and preclinical study demonstrated the statistic correlation of Hic-5 expression with HCC metastasis and the critical role of Hic-5 in the HCC progression. Patients and Methods: First, whether Hic-5 was a powerful prognosis marker of HCC progression was validated by more than a hundred clinical HCC samples. Second, whether Hic-5 played an essential role in HCC progression was confirmed both in vitro and in vivo using more patient-derived HCC cell lines. .37-6.98) were independent factors for survival in a multivariate analysis. The median survival of patients with (n = 40) and without PVT was 5.6 and 11.2 months (P < 0.001), respectively. There was no difference in survival between patients with (n = 31) and without extrahepatic metastases (9.6 vs 8.5 months, respectively; P = 0.784). The incidence of TACE-related complications was similar (P < 0.05, Table 1 # 2055 Successful treatment for hepatocellular carcinoma with extrahepatic lymph node metastasis by sorafenib combined with radiofrequency ablation and radiation therapy: A case report Authors: PO-HAO LIAO [1]; SHEN-YUNG WANG [1,2]; GWO-CHE HUANG [3]; HORNG-YUAN WANG [1]; TSANG-EN WANG [1,2,4]; SHOU-CHUAN SHIH [1,4]  Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is generally associated with hepatitis B or C virusrelated cirrhosis in Taiwan. Radiofrequency ablation (RFA) is an effective treatment against small solitary HCC. A multiple-electrode switching RFA system may achieve satisfactory control for HCCs larger than 3 cm. Patients with advanced HCC and extrahepatic metastasis are not good candidates for resection or locoregional treatments. Radiation therapy can provide local control for lymph node metastasis but cannot improve the prognosis. Sorafenib is associated with survival benefits in advanced HCC. Combination of sorafenib with other treatment modalities such as transarterial chemoembolization, RFA, or radiotherapy for HCC has shown additive effects or advantages. Case Description: A 62-year-old woman presented with HCV-related HCC which metastasized to a precaval lymph node. Both intrahepatic and extrahepatic lesions were larger than 5 cm. The intrahepatic HCC in S8 was treated with RFA using a multiple-electrode switching system. Radiation therapy was performed on lymph node metastasis. The patient concomitantly received a finite course of sorafenib. The intrahepatic HCC had been completely ablated, and the lymph node metastasis regressed. The patient has a recurrence-free survival for more than 3 years. With combination therapies of sorafenib, RFA, and radiotherapy, satisfactory outcomes can be achieved for advanced HCC with extrahepatic metastasis.
# 2070 Washout appearance could be a more important factor in prediction of small hepatocellular carcinoma with an atypical image pattern Authors:
Background: The chemokines/cytokines play important roles in the pathogenesis of chronic hepatitis C. However, their clinical characteristics and implications in treatment responses to pegylated interferon plus ribavirin treatment have not been fully illustrated yet. Aims: This study aims to investigate the predictability of the baseline serum concentrations of the chemokines/cytokines for the treatment responses to PegIFN/RBV for CHC. Methods: Patients with chronic genotype-1 hepatitis C infection who had been treated with PegIFN/RBV were enrolled. HCV genotyping and quantitation were performed. Sustained virological response (SVR), relapser, and non-responder (NR) were assessed according to international definitions. IL-28B genotyping was performed as well. Serum samples were analyzed by cytometric bead array. The seven analyzed chemokines and cytokines were CXCL9-11, CCL3-4, IL-10, and IFN-γ. Results and Discussion: There were 65 CHC GT-1 patients enrolled, including 27 (41%) with sustained viral responses, 16 (25%) relapsers, and 22 (34%) null responders. The patients with advantageous IL-28B genotype (rs12979860 cc genotype) were 49 (75%), and it was significantly higher in patients with SVR when compared with relapser and NR (P = 0.002). The baseline serum levels of CXCL10, CXCL11, CCL3, CCL4, IL-10, and IFN-γ were significantly higher in patients with NR when compared with SVR and relapsers (CXCL10: P = 0.002; CXCL11: P = 0.001; CCL3: P = 0.048; CCL4: P = 0.013; IL-10: P = 0.041; IFN-γ: P = 0.021). However, the serum levels of CXCL9 were significantly lower in patients with NR than SVR when compared with SVR and relapsers (P < 0.001). The predictors for NR in all these patients were IL-28B genotype (OR: 0.109, P = 0.002) and CXCL10 (OR: 0.995, P = 0.034). However, in patients with advantageous IL-28B genotype, CCL4 became the only predictor for NR (OR: 0.957, P = 0.013). Conclusions: The baseline serum level of CCL4 is the only predictor for NR in GT-1 CHC patients with favorable IL-28B genotype when treated with PegIFN/RBV. # 2141 Liver resection for hepatocellular carcinoma in cirrhotic patients with preoperative indocyanine green 15-min retention ≥ 30% Authors: LIN HUI-CHEN [1]; CHENG-CHUNG WU [1]; SHAO-BIN CHENG [1]; JOHN WANG [2] Affiliations: [1]Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan [2]Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan Purpose: Indocyanine green 15-min retention rate (ICG R15) has been a guide for liver resection feasibility. Generally, ICG R15 ≥ 30% means a considerable liver dysfunction. The role of liver resection and transplantation for hepatocellular carcinoma (HCC) in cirrhotic patient remained controversial. This study reviews our result of liver resection, especially to the HCC in cirrhotic patient whose ICG R15 ≥ 30%. Patient and Methods: A retrospective review of a prospectively collected data of liver resection for HCC in cirrhotic patients in 1993-2014 was carried out. According to preoperative ICG R15, these cirrhotic patients were divided into two groups, group 1 with preoperative ICG R15 < 29.9% (n = 1023) and group 2 with ≥ 30% (n = 115). Clinicopathological characteristics, early postoperative results, and long-term survival rate were compared. Those whose HCC fulfilled the Milan criteria for liver transplantation between both groups were selected for survival analysis (n = 522 for group 1 and n = 84 for group 2). Results: Group 2 patients had characterized by older age (P = 0.001), smaller tumor size (P = 0.0001), shorter operative time (P = 0.0012), higher Child-Pugh grade, and smaller resection weight (P < 0.0001). The blood loss amount, complication rates and 90-day mortality, and pathological characteristics did not significantly differ. Five-year disease-free (DF) and overall survival rates (OS) for groups 1 and 2 were 44.9% and 41.8% (P = 0.784) and 51.4% and 46.8% (P = 0.937) respectively. However, for those whose HCC fulfilled the Milan criteria, DF and OS for group 1 (n = 522) and group 2 (n = 84) were 60.5% and 49.4% (P = 0.023) and 77.3% and 65.1%, respectively. Conclusions: The HCC in selective cirrhotic patients requiring preoperative ICG R15 ≥ 30% is worthwhile for liver resection. However, for HCC that fulfilled the Milan criteria, transplantation may be first considered when their ICG R15 ≥ 30%.
# 2148 Safety margin index, rather than heat sink effect, determines the 1-year recurrence rate of a juxta-vessel hepatocellular carcinoma treated by radiofrequency ablation Authors: WEI-YANG LEE [1]; TSE-KAI TSENG [2]; CHIA-WEN SHIH [3]; PAI-HSUEN CHEN [4] Affiliations: [1] This work aims to study whether a dynamically wide safety margin RFA can overcome the HSE and yield low 1-year local recurrence rate (1YLR). Material and Methods: Safety margin index (SMI) was defined as (final prong extension width À maximal tumor width)/maximal tumor width. From Jan 2011 to Jan 2014, nine HCC cases with abutting major hepatic veins (HV) or portal veins (PV) (9 juxta-vessel HCC; JV) were retrospectively compared with nine Barcelona Clinic Liver Cancer stage Amatched cases (10 HCC with no adjacent vessels; NJV). SMI was maintained at > 0.5 for each RFA procedure in both groups. RFA was performed with a multi-prong probe (AngioDynamics), and the heating protocol was defined according to the manufacture's guide. The time ratio (TR) was defined as the "actual heating time/manufacturers' reference time" for a complete RFA procedure. The higher the TR indicated, the stronger the HSE. The mean RFA TRs of both patient groups were compared, as well as the 1YLR rates. The tumor sizes are 3.02 ± 0.65 and 2.89 ± 0.58 cm in the JV group and NJV group, respectively (P = 0.65). The SMI is 0.68 ± 0.31 versus 0.91 ± 0.27 (P = 0.102) in the JV and NJV groups. Result: (i)The resultant TR is 1.34 ± 0.47 versus 0.99 ± 0.33 (P = 0.033 < 0.05) in the JV group and NJV group, respectively. This indicates HSE does exist and significantly prolong the TR in the JV group.
(ii)A positive correlation exists between the vessel diameter and the HSE. That is, the slopes of the diameter-TR regression lines are positive for both HV (0.115) and PV (0.042). (iii)Provided SMI > 0.5, the 1YLRs are both low, 0/9 versus 2/10 (P = 0.17) in the JV group and NJV group, indicating that SMI > 0.5 overcomes the HSE. Conclusion: The "SMI > 0.5" precondition overcomes the HSE, resulting in a comparably good complete eradication rate and low 1YLR. Background and Aim: Barcelona Clinic Liver Cancer (BCLC) staging system links the stage of HCC status to a specific treatment strategy. The BCLC-C stage comprises a highly heterogeneous patient population. In this study, we aimed to stratify patients with advanced hepatocellular carcinoma (HCC) into different sub-stages and to identify possible prognostic predictors that might influence the overall survival amount of patients receiving sorafenib treatment. Method: We retrospectively reviewed data from August 2012 to May 2015 in the National Cheng Kung University Hospital of Taiwan. A total of 271 patients who were diagnosed as advanced HCC (BCLC stage C) receiving sorafenib were included. Patients' data were collected including etiology of HCC, baseline and on treatment response of α-fetoprotein (AFP), Child-Turcotte-Pugh (CTP) score, Cancer of the Liver Italian Program score, tumor status and behavior (including extra-hepatic metastasis and vascular invasion), local-regional therapy during sorafenib treatment, and side effect of sorafenib. All BCLC-C patients were sub-staged according to the pattern of vascular invasion, metastasis, and CTP score (Table 1). Overall survival and possible prognostic factors were analyzed. Result: The median survival was 303 days. The median survival (days) in C1:C2:C3 stages are 397 ± 29 versus 231 ± 29 versus 121 ± 22 days, respectively (all P < 0.01) (Fig. 1). The Cox regression analysis identified non-viral hepatitis (P ≤ 0.01), high baseline AFP (e.g., AFP > 400) (P < 0.01), and poor AFP response to sorafenib (P < 0.01) as prognostic factors to the survival of patients with advanced HCC. Conclusion: According to our study, the BCLC-C sub-staging system showed different survival in these heterogeneous population. The etiology of liver disease and the baseline and on treatment change of serum AFP levels were also related to patients' survival. # 2158 The autophagy marker LC3 is significantly associated with recurrence in human hepatocellular carcinoma undergoing resection Authors: CHIH-WEN LIN [1][2][3][4]; CHIA-YEN DAI [4,5]; JEE-FU HUANG [4,5]; WAN-LONG CHUANG [4,5]; MING-LUNG YU [4,5]  Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence, and is the third leading cause of cancer-related mortality in the world. Most HCC patients are diagnosed at an advanced stage and have very poor prognosis and low survival. Despite the improvements of therapeutic modalities in HCC, the rate of 5-year tumor-related death has remained as high as 30-50%. Therefore, identification of prognostic factors to develop newer targeted therapy is urgently needed to improve HCC patient survival. Autophagy is a process through which long-lived proteins and damaged organelles are conveyed to the lysosome for removal by degradation and recycling. Some studies have shown that autophagy plays a key role in the progression and development of cancer. But the role of autophagy in the prognosis and metastasis of human HCC is not well known. Aims: The study aims to explore the expression of markers of autophagy genes using immunohistochemistry (IHC) in human HCC tissues. We also investigate the autophagy markers associated with clinicopathological characteristics and prognosis. Background: Patients with liver cirrhosis experience symptoms and concerns that negatively impact their quality of life. This study aims to examine the health-related quality-of-life (HRQL) in patients with liver cirrhosis. Methods: A cross-sectional study was conducted in the gastroenterology wards and clinics of the Singapore General Hospital. Thirty-five cirrhotic patients and 24 chronic hepatitis patients were recruited as case and control groups, respectively. Patients with significant comorbidities were excluded. The Chronic Liver Disease Questionnaire (CLDQ) was used to assess the HRQL of these patients, and mean CLDQ score was used as the primary outcome measure. Results: Cirrhotics were older and had lower educational status compared to non-cirrhotic controls. Of cirrhotics, 57% were Child A, 29% Child B, and 14% Child C. Overall mean CLDQ scores were lower in cirrhotics compared to controls (5.04 ± 1.12 vs 5.84 ± 1.07, P = 0.008) with 49% of cirrhotics having poor HRQL (defined as mean CLDQ score < 5) compared to 21% of controls. Significant differences were found in the activity, emotional, and worry domains but not in the abdominal, fatigue, and systemic symptom domains. CLDQ scores in cirrhotics < 60 years old were significantly lower than those in > 60 ( Introduction: Oxidative stress is defined as an imbalance between prooxidant and anti-oxidant mechanisms in our body. Oxidative stress has been implicated in the pathogeneses and in many fibroproliferative diseases such as cirrhosis, atherosclerosis, and pulmonary fibroses. Aim: We studied oxidative stress in patients with cirrhosis by measuring serum superoxide dismutase (SOD), serum catalase, and serum thiobarbituric acid reactive substance (TBARS) and compared these with those in normal healthy controls. Design: This is a case-control prospective study. Materials and Method: Thirty patients of proven cirrhosis along with 20 age-matched and sex-matched healthy controls were included in our study. Exclusion criteria were coexisting diabetes, chronic kidney disease, coronary artery disease, recent acute illness, hospital admission, and use of anti-oxidant drugs and statins. Beside routine investigations, serum SOD, serum TBARS, and serum catalase levels were measured by standard methodology and compared with those in controls. Statistical Analysis: Continuous variables were recorded as mean ± SD, and ANOVA test was used to evaluate P values among the groups. Results: Cirrhotic patients showed a significant increase in serum TBARS (0.267 ± 0.1330) and serum catalase (3.502 ± 0.458) when compared to controls (0.0964 ± 0.018621 and 2.0278 ± 0.016, respectively), with a P value < 0.001. There was a significant decrease in level of SOD (2.74 ± 0.6449) compared with that controls (4 ± 0.380058), with a P value < 0.001. Conclusion: This study indicates that there is increased lipid peroxidation and oxidative stress as observed by an increased level of serum TBARS catalase with a decreased level of SOD levels. As more studies continue to emerge regarding the role of oxidative stress in disease development and the mechanisms underlying cellular toxicity, these findings will lead to more rational anti-oxidant therapeutic approaches. Further large clinical trials are necessary to confirm whether drugs targeting oxidative stress like anti-oxidant supplementation become a magical pill for treatment of cirrhosis and its complication.
# 1516 Inhibition of hepatic tumor necrosis factor-α attenuates anandamide-induced vasoconstrictive response in cirrhotic rat livers Authors: TZU-HAO LI [2,4]; YING-YING YANG [3,4]; KUEI-CHUAN LEE [1,4]; YUN-CHENG HSIEH [1,4]; PEI-CHANG LEE [1,4]; HAN-CHIEH LIN [1,4]  Background: Increased anandamide, an endocannabinoid which interacts with both cannabinoid CB 1 and CB 2 receptors, can induce hepatic vasoconstrictive responses which contribute to the increased intrahepatic resistance (IHR) in cirrhotic rats. Chronic endotoxemia and subsequent release of tumor necrosis factor-α (TNF-α) are suggested to result in increased anandamide in cirrhotic livers. Thalidomide, inhibiting TNF-α effectively, has been used clinically in states of chronic TNF-α elevation with encouraging results. Aims: This study wants to explore the possible effects of thalidomide on hepatic endocannabinoids and microcirculation of cirrhotic rats. Methods: Portal venous pressure (PVP), superior mesenteric arterial blood flow (SMA BF), hepatic TNF-α, interleukin (IL-6), protein expression of CB 1 and CB 2 receptors, and thromboxane synthase (TXS) were measured in bile duct-ligated (BDL) rats receiving 1 month of vehicle (BDL-V) or thalidomide (BDL-thalido). Degree of hepatic fibrosis was also assessed. In liver perfusion system, IHR and concentration-response curves of portal perfusion pressure to anandamide were evaluated. Results: In BDL-thalido rats, PVP, IHR, and hepatic levels of TNF-α and IL-6, protein expression of CB 1 receptors, TXS, and hepatic fibrosis were lower than in BDL-V rats. In BDL-thalido rat livers, the attenuation of vasoconstrictive response to anandamide was associated with an upregulation of CB 2 receptor and a downregulation of CB 1 receptors. Nevertheless, SMA BF was not different between BDL-thalido and BDL-V rats. Conclusions: Thalidomide decreased the PVP and IHR through the prevention of hepatic fibrosis, attenuation of anandamide-induced constrictive response, and a decrease in the production of TNF-α, IL-6, and TXA 2 in the liver of rats with biliary cirrhosis in this study. Discussion: Using biliary cirrhosis rat's model, we found that inhibition of hepatic TNF-α by administration of thalidomide decreased the PVP and IHR through the prevention of hepatic fibrosis, attenuation of hepatic anandamide-induced constrictive response via upregulation of hepatic CB 2 receptor and a downregulation of hepatic CB 1 receptors, and a decrease in the production of TXA 2 .
Keywords: anandamide, tumor necrosis factor-α, vasoconstriction. # 1607 Plasma levels of matrix metalloproteinase 2 and 9 in male and female patients with cirrhosis of different etiologies Authors: CHENG-CHUAN SU [1][2][3]; KUO-CHIH TSENG [3,4]; MING-NAN LIN [3,5]; JEN-PI TSAI [3,4,6] Affiliations Introduction: Liver fibrosis and cirrhosis may be reversible in some circumstances. Reliable diagnostic tests are necessary for monitoring hepatic fibrogenesis. Matrix metalloproteinase (MMP)-2 and MMP-9 are two of the major MMPs in the circulation and may be most relevant to hepatic fibrosis. The behavior of MMPs may be significantly different in men and women and may also differ in cases of cirrhosis of various etiologies. This study aimed to evaluate the manifestations of MMP-2 and MMP-9 in liver cirrhosis of different etiologies in men and women and to compare these patterns with those of healthy controls. Materials and Methods: We measured MMP-2 and MMP-9 levels in plasma samples from 112 patients with cirrhosis and 112 age-matched and gender-matched healthy controls. We then correlated these MMP levels with gender and disease etiology. Results: Plasma MMP-2 concentrations in patients showed a trend towards increasing values with cirrhosis severity and were markedly increased in patients regardless of gender and etiology compared with healthy controls (P < 0.0001). Plasma mean MMP-9 levels were comparable in patients with cirrhosis and controls but increased with disease severity. They were significantly lower in patients, female patients, and male patients with mild cirrhosis than in controls, female controls, and male controls (P = 0.001, 0.041, and 0.009, respectively). MMP-2 and MMP-9 concentrations were not significantly different between genders among controls and among various patient subgroups. Conclusions: Plasma MMP-2 level may be a useful diagnostic marker for monitoring hepatic fibrogenesis in patients with disease of different etiologies. Tc lung perfusion and portal hypertension, and assessed the roles of 99m Tc lung perfusion in severity of the conditions. Methods: The clinical records of 14 patients diagnosed with liver cirrhosis were reviewed. 99m Tc lung perfusion imaging was conducted in all patients. Results and Discussion: Six males and eight females, the medium age of whom was 55.5 years (24-77), were included in this study. Eight cases showed positive lung perfusion imaging. The Child-Pugh classification was from A to C, and the shunt rate in pulmonary perfusion was from 5.4% to 39.3%. No patients revealed clinical manifestations of hepatopulmonary syndrome. Thirteen patients had varices bleeding. Eleven patients had ascites. Compared with the negative group, patients in the positive group were inclined to have a higher Child-Pugh score and higher incidence of gastric varices. In abdominal ultrasound and computed tomography (CT) scanning, the average diameter of the portal vein was 14.03 and 16.00 mm in the positive and negative groups, respectively. The average thickness of the spleen was 4.95 and 5.33 cm in the positive and negative groups, respectively. The average minimum platelet count was 55.38 * 10 9 /L in the positive group and 50.33 * 10 9 /L in the negative group. Thrombosis in the portal vein was found in three cases in the positive group and two cases in the negative group. Conclusions: The positive results of 99m Tc lung perfusion scanning might have certain relationships with Child-Pugh classification, gastric fundus varices, ascites, and the degree of thrombocytopenia in cirrhosis patients. Besides, it might be negatively correlated with the diameter of portal vein. It might have an important role in the assessment of severity of liver cirrhosis and predicting the degree of portal hypertension.   Background/Aims: Tolvaptan had been approved in cirrhotic patients with ascites and insufficient response to conventional diuretics in Japan. The objectives were to investigate the improvement of symptom and nutritional status by tolvaptan use in cirrhotic patients. Methods: Support Team Assessment Schedule (STAS-J) which consists of five grades was used to evaluate bloated feeling. Its symptomatic responder was defined as improvement of one grade or more. Controlling nutritional status (CONUT) is based on serum albumin level, total lymphocyte count, and total cholesterol level. CONUT, which consists of 13 grades, was used to evaluate nutritional status. Body weight and serum electrolyte were measured; further, concomitant use of drugs and dietary intake were recorded. Additionally, the predictive factors which affected the symptomatic responder of tolvaptan were confirmed. Results: Eligible for enrollment were 32 patients with liver cirrhosis including males/females (12/20), 68.3 ± 14.4 years old, with Child-Pugh classification B/C (10/22) and Child-Pugh score of 10.2 ± 1.5. Reduction in body weight was 4.0 ± 3.7 kg. The STAS-J score was improved in 19 patients (59.4%). The CONUT score in responders was significantly improved compared to non-responders (7.9 ± 2.1 vs 10.1 ± 1.9, P < 0.01, respectively). Dietary intake in responders significantly increased (P < 0.01). Serum sodium concentration at baseline was the most reliable Introduction: It has been suggested from prospective studies that excess body weight may result in a substantial increase in the risk of liver fibrosis. Transient elastography (FibroScan) is a novel non-invasive modality which has now been proven to assess liver fibrosis with high sensitivity. We conducted this study to assess the stage of liver fibrosis on FibroScan in patients with a body mass index (BMI) of more than 28, irrespective of the underlying cause of liver disease. Introduction: Dysregulated erythropoietin plasma levels may play a role in the pathophysiology of chronic liver disease because chronic anemia is frequently observed in patients with liver cirrhosis. Some reports have used regular erythropoietin and filgrastim in liver cirrhosis patients with benefits to patients. There is no report of use of long-acting erythropoietin (darbepoetin alpha) and pegylated filgrastim (pegfilgrastim) in patients with liver cirrhosis. Aims and Methods: This work aims to study the benefits of darbepoetin and pegfilgrastim in patients with advanced liver disease (Child C status). Prospective patient inclusion and all the hematological, biochemical, ultrasound, and clinical parameters were recorded. Patients with active bleeding, confirmed hepatorenal syndrome, hepatoma, portal vein thrombosis, and splenic vein thrombosis were excluded from the study. The study started from October 2014 onwards, patients started on injection darbepoetin alpha 200 μg and injection pegfilgrastim 6 mg subcutaneously every 15 days, with a total of three injections, and a minimum of 3 months' follow up was planned. Improvement in hematological, coagulation, biochemical, clinical parameters, and Child score was analyzed. For statistical analysis, the median was calculated for nonparametric variables, and a Kruskal-Wallis nonparametric test was done on SPSS version 12 statistics software. Results and Discussion: A total of 12 patients were included in study, and three were lost to follow up, all of whom were male. Etiology of cirrhosis was non-alcoholic fatty liver disease in two, hepatitis B virus cirrhosis in one, hepatitis C virus in one, and alcohol in eight patients. Median age was 54 years (range 50-66 years). There was an improvement in median hemoglobin from 8.7 to 10.6 g % (Z value 1.96, P value 0.05), total leukocyte count improved from 4700 to 7100/mm 3 (Z value 2.13, P value 0.033), platelet count improved from 60 000 to 188 000/mm 3 (Z value 2.668, P value 0.008), international normalized ratio improved from 1.8 to 1.4 (Z value 2.668, P value 0.008), serum albumin improved from 2.1 to 2.4 g/dL (Z value 2.028, P value 0.043), and Child score improved from 10 to 8 (Z value 2.694, P value 0.007). There was no significant improvement in serum creatinine, sodium, potassium, calcium, bilirubin, total protein values and clinical scores of ascites, and hepatic encephalopathy. One patient developed fever with respiratory tract infection which led to decompensation, which affected all the reports. High cost of medicine was the limiting factor to include more patients in study. Conclusion: Initial data suggest that darbepoetin alpha and pegfilgrastim are significantly effective in improving hemoglobin, total leukocyte count, platelet count, international normalized ratio, serum albumin, and Child score of the patients with advanced liver cirrhosis.

# 1775 Predicting risk factors for rebleeding,
Introduction: Cirrhosis is associated with poor outcomes in peptic ulcer bleeding (PUB) and very few large population-based studies in the literature. This nationwide cohort study aimed to elucidate the association between cirrhosis and recurrent PUB, mortality by analyzing the Taiwan National Health Insurance Research Database. Methods: Data of 1997-2008 were extracted from the National Health Insurance Research Database in Taiwan. A total of 18 646 discharges with PUB as a diagnosis were identified. Patients < 20 years of age and patients who underwent bleeding with endoscopic treatment within 180 days before index, varices bleeding, gastric resection, vagotomy, or gastric cancer before index hospitalization discharge were excluded (n = 533). In this population-based cohort study, 737 cirrhotic patients, 1044 chronic hepatitis patients, and 13 794 normal controls were compared. Results: In this study, cirrhotic patients had significantly higher incidences of recurrent PUB than chronic hepatitis patients and controls (12.48% in cirrhosis, 6.7% in chronic hepatitis, and 5.61% in controls, P < 0.0001). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of recurrent PUB (hazard ratio: 2.42; 95% confidence interval [CI]: 1.88-3.21, P < 0.0001) after adjusting for age, gender, Charlson score, and ulcerogenic medication. Male gender, repeated endoscopic therapy, infection, severe ulcer bleeding, and use of aspirin were risk factors for inhospital recurrent PUB in all patients. Age, male gender, Charlson score ≥ 2, severe ulcer bleeding, and use of aspirin/nonsteroidal antiinflammatory drugs were risk factors for in-hospital death in all patients. Mortality of PUB with concomitant cirrhosis was higher than that in the chronic hepatitis group and controls (P = 0.01 and P = 0.04, respectively). In multivariate analysis, the presence of cirrhosis independently increased long-term mortality (hazard ratio: 1.97; 95% CI: 1.68-2.32, P < 0.0001), but not in-hospital death. Patients with cirrhosis received more transcatheter arterial embolization for recurrent PUB compared with the other two groups (7.6% vs 2.6% vs 0.7%, respectively). Hospitalization costs and length of stay also were increased in patients with cirrhosis.
Conclusions: This study suggests that cirrhotic patients are associated with a significantly higher risk of recurrent PUB. Liver cirrhosis is also associated with long-term risk of mortality after hospital discharge. Background: Recent studies have shown that microRNA-29 (miR-29) is significantly decreased in liver fibrosis and that its downregulation influences the activation of hepatic stellate cells (HSCs). In addition, inhibition of the activity of histone deacetylases 4 (HDAC4) has been shown to strongly reduce HSC activation in the context of liver fibrosis. Objectives: In this study, we examined whether miR-29a was involved in the regulation of HDAC4 and modulation of the profibrogenic phenotype in HSCs. Methods: We employed miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates to clarify the role of miR-29a in cholestatic liver fibrosis, using the bile duct ligation (BDL) mouse model. Primary HSCs from both mice were treated with a miR-29a mimic and antisense inhibitor in order to analyze changes in profibrogenic gene expression and HSC activation using real-time quantitative reverse transcription-polymerase chain reaction, immunofluorescence staining, western blotting, and cell proliferation and migration assays. Results: After BDL, overexpression of miR-29a decreased collagen-1α1 and HDAC4 and activated HSC markers of glial fibrillary acidic protein expression in miR-29aTg mice compared to wild-type littermates. Overexpression of miR-29a and HDAC4 RNA interference decreased the expression of fibrotic genes, HDAC4 signaling, and HSC migration and proliferation. In contrast, knockdown of miR-29a with an antisense inhibitor increased HDAC4 function, restored HSC migration, and accelerated HSC proliferation.

Conclusions:
Our results indicate that miR-29a ameliorates cholestatic liver fibrosis after BDL, at least partially, by modulating the profibrogenic phenotype of HSCs through inhibition of the HDAC4 function.
# 1789 Low air temperature increases the risk of esophageal variceal bleeding: A population and hospital-based case-crossover study in Taiwan  # 1834 Acoustic radiation force impulse sonography-based non-invasive prediction of esophageal varices Authors: CHI-CHIH WANG [1,2]; MING-CHANG TSAI [1,2]; TZU-WEI YANG [1]; CHING-BIN LIN [1,3]; TZY-YEN CHEN [1]; CHUN-CHE LIN [1,3]  Eighty-five patients were clinically diagnosed with liver cirrhosis, and the other 33 were diagnosed with chronic liver disease. In cirrhosis patients, half of them ever received EGD within 1 year before ARFI examination. Variables found to be associated with the presence of esophageal varices on univariate analysis (P < 0.05) were entered into the multivariate logistic regression analysis. The optimal cut-off value for esophageal varices prediction was calculated under the receiver operating characteristic curve. Result: In the cirrhosis group, spleen stiffness was higher in patients with EV (3.43 ± 0.44 m/s, n = 26) than NEV (3.03 ± 0.68 m/s, n = 16; P = 0.043). SS and spleen diameter meet significant difference in multivariate analysis for EV prediction (P = 0.035 and P = 0.037, respectively), shown in Table 1. Based on area under the receiver operating characteristic curve analysis, for EV prediction, spleen diameter with the optimal cut-off value of 10.69 cm showed a sensitivity of 96.2% and specificity of 56.3%; SS with the optimal cut-off value of 2.82 m/s showed a sensitivity of 96.2% and specificity of 50% (Fig. 1). A relaxed new cut-off criterion, spleen diameter ≥ 10.69 cm or SS ≥ 2.82 m/s, was introduced with 100% negative predictive value and 100% sensitivity. Conclusion: Spleen diameter and SS together can provide powerful diagnostic performance in selecting cirrhosis patients who have EV formation. Figure 1 Proposed model of miR-29a signaling protection in liver fibrosis and HSC activation. miR-29a is an important regulator of the profibrogenic phenotype of HSCs. By suppressing HDAC4 action, miR-29a increases H3K9 acetylation and suppresses Smad3 phosphorylation, therefore inhibiting the activation of HSCs. Background/Aims: Liver fibrosis is a common consequence of chronic liver injury that is induced by a variety of etiological factors. The present study aimed to test the hypothesis that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potential target of liver fibrosis. Materials and Methods: HB-EGF transgenic (TG) mice and wild-type (WT) mice were used. Liver fibrosis was induced by intraperitoneally injection of carbon tetrachloride (CCl 4 ). H&E, Sirius red, and α-SMA immunohistochemical staining were performed in the liver sections of TG and WT mice. Primary hepatic stellate cells (HSCs) isolated from two types of mice were used. The proliferative capacity and the degree of apoptosis of primary HSCs were evaluated. RT-PCR was used to test for mRNA levels of α-SMA, collagen 1α1, TIMP-1 and MMP-13 both in the liver sections and the primary HSCs. The protein levels of EGFR, p-EGFR, ERK and p-ERK in the liver sections were detected by Western blot. Results: The mRNA levels of HB-EGF, α-SMA, collagen 1α1, and TIMP-1 were elevated in TG mice compared to WT mice. Liver fibrosis in TG mice was more significantly amplified with more deposition of collagen and increased expression of α-SMA and fibrogenic genes. Compared with WT mice, increased protein levels of p-EGFR and activated ERK were found in TG mice. HSC from TG mice showed enhanced activation and reduced apoptosis as well. Conclusions: HB-EGF overexpression contributes to the progression of liver fibrosis and exerts profibrotic roles. Therefore, HB-EGF is a potential therapeutic target in liver fibrosis. Background/Aims: Increasing hepatic stellate cell (HSC) death is an attractive approach for limiting liver fibrosis. The multiple tyrosine kinase inhibitor sorafenib has recently demonstrated anti-fibrotic effects in vitro and in vivo. However, the precise molecular mechanism through which sorafenib mediates this activity is unknown. Methods: We investigated the mode of cell death induced by sorafenib and its underlying mechanism in primary rat HSC and human LX2 cells. Apoptosis and autophagy were monitored by using morphological methods, such as transmission electron microscopy and immunofluorescence. Western blot analysis confirmed these findings. Results: Sorafenib induced apoptosis in a dose dependent manner in LX2 cells. Ultrastructural analysis revealed that rat HSCs treated with sorafenib accumulated residual digested material and empty or autophagic vacuoles. Incubating LX2 cells with lysosomal protease inhibitors increased the accumulation of LC3-II, indicating that sorafenib enhances autophagic flux in HSCs. This conclusion was confirmed by the observed upregulation of Beclin 1, Atg7, and Atg5. In LX2 cells treated with sorafenib, expression of cleaved-PARP increased significantly, whereas levels of LC3-II peaked at 12 h and reverted to baseline by 24 h. These findings indicate that autophagy may precede apoptosis. Inhibition of autophagy in LX2 cells via 3-MA treatment or siRNA-mediated knockdown of Atg5 resulted in a marked increase in apoptosis. Finally, Sorafenib induced programmed cell death by attenuation and activation of Akt/mTOR/ p70S6K and JNK signaling, respectively. Conclusions: These results demonstrate that sorafenib-induced cell death is mediated autophagic cell death and apoptosis, which could potentially result in novel anti-fibrosis therapies.

Viral Hepatitis
# 1022 Sequential treatment with lamivudine and peginterferon therapy in patients with E antigen-positive chronic hepatitis B and high viral load Authors: SHOU-WU LEE [1,2]; SHENG-SHUN YANG [1,3], TENG-YU LEE [1,2]; CHI-SEN CHANG [1]; HONG-ZEN YEH [1,3] Affiliations: [1] Background: The aim of this study was to assess the therapeutic response of sequential therapy, lamivudine (LAM) followed by PEG-IFN, in the patients with e antigen-positive chronic hepatitis B (CHB) and high viral load. Methods: CHB patients who have positive e antigen, HBV DNA greater than 10 7 IU/mL, ALT levels greater than 2 times the upper limit, and treatment naive were included. Those with concurrent hepatitis C or HIV infection, liver cirrhosis or decompensated liver disease, or pregnancy were excluded. The enrolled cases received therapy with PEG-IFN monotherapy for 48 weeks (PEG-IFN group) or sequential therapy with lamivudine (LAM) for 4 weeks followed by PEG-IFN therapy for 48 weeks (LAM/peg-IFN group). Results: There were 10 patients in each group, and there were no differences in characteristics between the two groups. The positive response ratio of end-of-treatment (EOT) was 30% and 10% in the PEG-IFN group and the LAM/PEG-IFN group. Sustained off-treatment virological responses (SVR) at 12 weeks after EOT were 40% and 10%, at 24 weeks after EOT were 30% and 20% in the PEG-IFN group and the LAM/PEG-IFN group, respectively. The therapeutic responses between the two groups showed no differences. Conclusion: In CHB patients who have positive e antigen and a high viral load at baseline, similar therapeutic responses were noted between the sequential therapy group and the PEG-IFN monotherapy group. Further research with a higher number of patients and a prolonged LAM course are needed to confirm the efficacy of this approach.  Data reported to three significant figures. †One subject withdrew from the study on day 2, did not have PK samples collected and is not included in the PK analysis. ‡N = 2113 (LDV/SOFUSNDA population). §N = 36 (Taiwanese population) or 1542 (overseas LDV/SOF population).
Conclusion: There were no clinically relevant differences in the PK of LDV/SOF in Taiwanese subjects compared to historical data. PK results in conjunction with safety and efficacy data support the use of LDV/SOF 90 mg/400 mg 12 weeks for the treatment of GT1 HCV infection in Taiwanese  Aim: This open-label, Phase 3 study evaluated the efficacy and safety of ledipasvir 90 mg/sofosbuvir 400 mg Fixed-Dose Combination (LDV/SOF FDC) ± ribavirin (RBV) administered orally, once daily for 12 weeks in treatment-naïve and treatment-experienced Japanese subjects with chronic genotype 1 hepatitis C virus (HCV) infection. Methods: Eligibility requirements included: age ≥20 years; HCV-RNA ≥10 5 IU/mL; platelets ≥50 000/μL. Primary endpoint was Sustained Virologic Response 12 weeks after treatment completion (SVR12). Results: 341 Japanese patients were enrolled (166 treatment-naïve and 175 treatment-experienced). Mean age was 59 years; 42% were male; 22% had cirrhosis; mean baseline HCV-RNA was 6.6 log 10 IU/mL. All patients in both arms had HCV RNA < LLOQ at weeks 4-12 of treatment. SVR12 was achieved in 100% (171/171) of patients in the LDV/SOF group and 98% (167/170) of patients in the LDV/SOF + RBV group. In the LDV/SOF + RBV group, one subject relapsed, one discontinued RBV due to a RBV-related rash, and one died due to cardiac arrest. All treatment-experienced patients achieved SVR12 regardless of previous HCV regimen or previous treatment response. Treatment-emergent adverse events (TEAEs) were reported by 65% of patients in the LDV/SOF arm and 75% in the LDV/SOF + RBV arm, with the most frequent being nasopharyngitis (29% and 24%, respectively) and anemia (2% and 14% respectively). Most TEAEs were mild to moderate in severity. Conclusions: LDV/SOF FDC ± RBV for 12 weeks achieved SVR12 in 99% of patients. LDV/SOF for 12 weeks provides a highly effective, well-tolerated, interferon-and RBV-free treatment for Japanese patients with chronic HCV GT1 infection. Background: Administration of sofosbuvir (SOF) + ribavirin (RBV) once daily for 12 weeks achieved an overall SVR12 rate of 100% (87/87) in treatment-naïve and treatment-experienced genotype 2 HCV-infected Taiwanese patients with or without cirrhosis (Phase 3b: GS-US-334-0115). Pharmacokinetic (PK) data were collected in the study to examine the relationship between demographic variables and exposure response and to compare results to studies conducted across various regions. Methods: Treatment-naïve (N = 43) and treatment-experienced (N = 44) Taiwanese subjects were enrolled and received SOF 400 mg + RBV (weight-based dosing) for 12 weeks. Sparse samples were collected to evaluate the pharmacokinetics of SOF and GS-331007 (predominant circulating metabolite). Exposure estimates for SOF and GS-331007 were generated for each subject, with measureable concentrations of SOF or GS-331007, using previously established population PK models. The effect of demographic variables on SOF and GS-331007 exposure was evaluated. Results: Table 1 presents steady-state exposure for SOF and GS-331007. Compared to historical data (overseas Phase 2/3 SOF population), SOF and GS-331007 exposures were similar between the two populations. Within the Taiwanese study population, no clinically relevant differences were observed in the PK of SOF or GS-331007 based on CLcr, age, sex, BMI, cirrhosis, prior treatment experience, or SVR12 outcome. Conclusion: SOF and GS-331007 exposures were similar in Taiwanese subjects compared to historical data. PK results in conjunction with safety and efficacy data support the use SOF 400 mg + RBV (weight-based dosing) for the treatment of GT2 HCV infection in Taiwanese patients. Introduction: The hepatitis C virus (HCV) infection is a serious public health problem in the world. In Taiwan, the most prevalent genotype was 1b, followed by genotypes 2a and 2b. The regional difference of genotype distribution might exist within different areas in Taiwan. The racial diversity of Taitung is heterogeneity and is a distinguishing feature. How the racial differences influence the genotype distribution is not well studied. The aim of this study is to determine the HCV genotype distribution and clinical implication in southeastern Taiwan. Methods: In this retrospective study, we included total 343 patients who had treated with peginterferonalpha plus ribavirin from Nov 2009 to Mar 2015. The data of genotypes, races, HCV viral load, and laboratory examination were collected and analysed (Table 1). Results/Discussion: The predominant HCV genotype in southeastern was type 1 (43.7%, including type 1b 36.4%), followed by type 2 (37.0%, including type 2a 26.8%) (Fig. 1). The proportion of patients mixed with genotype 1 is lower in indigenous group than nonindigenous group (46.1% and 60.2%, P = 0.02) (Fig. 2). The prevalence of genotype 6 (5.2%) in southeastern Taiwan seems higher than other area, but there is no difference between indigenous and non-indigenous people. Taiwanese indigenous people belong to Austronesian families. The Austronesian people are mainly in the South Pacific islands, including Taiwan, Vietnam, the Philippines, Malaysia, and so on. HCV genotype 6 is restricted to South China, Southeast Asia and in migrant patients from endemic countries [4].The association between Austronesian people and genotype distribution was still unclear. Conclusions: In southeastern area, HCV genotype 6 appeared slightly higher than general population in Tai Background: Hepatitis C virus (HCV) is known to evade host's immune responses efficiently. In virus-infected cells, antigen is processed by proteasome complex and presented to CD8+ T cells by major histocompatibility complex (MHC) class I. Interferon (IFN) switches conventional proteasomes to immunoproteasomes, which are more suitable for generation of MHC class I epitopes. Herein, we studied the effect of HCV infection on immunoproteasome production and its mechanism. Methods: JFH-1 (genotype 2a) HCV cell culture system was used for in vitro infection of Huh-7.5 cells. Huh-7.5 cells were treated with IFN-γ to induce immunoproteasome production. The expression of immunoproteasome subunits was evaluated by immunoblots and real-time PCR. The expression of protein kinase R (PKR) was silenced with lentiviruses that express small hairpin RNAs, and immunoproteasome induction was examined in PKR silenced cells. The peptide digestion was assessed in each cell group by mass spectrometry. Results: IFN-γ induced the expression of immunoproteasome subunits (immunosubunits) such as β1i (LMP2), β2i (MECL-1), and β5i (LMP7). However, IFN-γ-induced immunosubunits expression was attenuated in HCV-infected cells. While this attenuation in HCV-infected cells was observed at the protein level, it was not at the mRNA level. This result suggests that IFN-γ-induced immunosubunits expression is hampered during translation in HCV-infected cells. The expression of immunosubunits was restored by PKR silencing in HCV-infected cells, demonstrating that the PKR pathway is responsible for the suppression of immunosubunits expression in HCV-infected cells. Also this attenuated immunoproteasome expression by HCV infection resulted in decreased peptide production. The results are illustrated in Table 1. Genotypes 3 and 1 were predominant followed by genotypes 4 and 6. Statistical evaluation of the demographic of HCV patients stratified by genotypes did not revealed any significant difference between the two periods. There was no association between the risk factors analyzed and the acquisition of different HCV genotypes. However, there was significant difference for the treatment received in the second cohort (P < 0.005). Conclusion: There was more male, Malay ethnic, and IVDU patients seen in the latter cohort. The genotype distribution remains similar although there was slightly more genotype 3 in the latter years. The proportions of patients in the latter period receiving treatment were significantly higher. Background/Aims: The purpose of this study is to evaluate the predictive factors by examining the treatment effects and responses in patients with chronic hepatitis B after a 6-month period of tenofovir rescue therapy. Methods: The medical records of 68 patients who had undergone a sixmonth treatment of tenofovir were analyzed. Those patients had previously been identified with drug resistance mutations from September 2012 through August 2014. The virological response showed a decrease in a value of less than 20 IU/mL of HBV DNA and the Partial virological response showed a decrease in value over a 1log baseline of HBV DNA, while throughout the trial, HBV DNA was continuously detected. Results: After 24 weeks 36 patients (53%) showed a virologic response, and 29 patients (43%) showed a partial virological response. Compared with virological response patients, the partial virological response patients showed a higher HBeAg positive rate (P < 0.001) of HBV DNA with the baseline (P < 0.001) and showed a significant difference. The results of the analysis showed that the low amount of HBV DNA (P < 0.001) and serum HBeAgnegative status (P = 0.004) was independent factor to predict virological response at 24 weeks after tenofovir rescue therapy. Conclusions: Tenofovir rescue therapy showed a positive therapeutic effect in drug-resistant chronic hepatitis B patients. And baseline low HBV DNA levels and HBeAg negative status is useful in predicting the virological response of tenofovir rescue therapy.
# 1384 Validation of increased liver size by ultrasonography after nucleos(t)ides analogs for treatment of chronic hepatitis B-A non-invasive exam for evidence of liver histological improvement Authors: RH CHANG [1]; G SARVESH [1,2]; T NYAMSUREN [3]; YW HUANG [1,[4][5][6]; SC FU [1]; SS YANG [1,7]  Background: To evaluate the stage of liver damage prior to, during and after treatment of patients of Chronic Hepatitis B (CHB), liver biopsy has been the most reliable method of ascertaining the stages of liver damage; albeit not without the disadvantage of being invasive. Histological improvement and regression of liver fibrosis or cirrhosis after long-term use of nucleos(t)ides analogs (NUCs) have been reported. The aim of present investigation is to evaluate the feasibility of parameters demonstrated in ultrasonography as evidences to validate histological improvement of liver after NUCs therapy in CHB patients. Methods: A total of 181 patients of CHB, who were subjected to long-term NUCs treatment, in Cathay General Hospital, were used as the basis of this study; every patient having had tests at the baseline and the endpoint of treatment period. The study population was divided into three groups, cirrhotic, non-cirrhotic, and healthy hepatitis B virus (HBV) carrier. The changes in the percentages of liver size, liver edge, spleen size, platelet count, and platelet count/spleen diameter (PC/SD) ratio were obtained, and compared with the mean differences of different stages of liver damage. Results: The mean averages of liver sizes, liver edges, spleen sizes, platelet count, and PC/SD ratio in healthy CHB carriers, non-cirrhotics and cirrhotics were 7.33, 6.93 and 6.34 cm; 39.09, 35.98 and 37.74; 8.69, 9.09 and 10.79; 212.52, 166.03, and 125.58; and 2477.22, 1880.58 and 1329.08 respectively; thus exhibiting trends that could be seen as developing to cirrhosis. Decrease in spleen size exhibited a linear relationship when compared with the treatment period (coefficient of determination, R 2 = 0.905). Conclusions: Comparing outcomes of healthy HBV carrier, non-cirrhotic, and cirrhotic patients, demonstrated histological improvement of liver after NUCs therapy in CHB patients.
# 1400 Association of a sustained virologic response with a reduced progression rate to esophageal varices in cirrhotic patients with chronic hepatitis C Authors: SHIH-HSIN LIANG [1,2]; CHIH-WEI TSENG [2,3]; TSUNG-HSING HUNG [2,3]; KUO-CHIH TSENG [2,3]; YU-HSI HSIEH [2,3]  Introduction: Chronic hepatitis C (CHC) is an important cause of liver cirrhosis. Esophageal variceal (EV) is a potentially fatal complication in cirrhotic patients. The achievement of a sustained virologic response (SVR) through interferon-based therapies can slow the progression of liver fibrosis. It is important to know the association of a SVR with a reduced progression rate to EV in cirrhotic patients with CHC. Background and Aims: To study the effect of SVR on the progression of EV in compensated cirrhotic patients with CHC after combination treatment. Methods: Ninetyeight treatment-naïve CHC compensated cirrhotic patients who underwent combination treatment of pegylated-interferon (PEG-IFN)/ribavirin, from January 2005 to December 2011, were enrolled in this retrospective study. All the patients were examined with abdominal ultrasonography and liver biochemistry at baseline, the end of treatment, and every 3-6 months post-treatment. The frequency of surveillance endoscopies in cirrhotic patients was according to the EV guideline of AASLD. Results: The mean age of 98 cirrhotic patients without baseline esophageal varices was 58.0 ± 10.5 years. The average following-up time of each patient was 4.43 years (standard deviation: 1.74 years, range: 1.13 -9.27 years). Fifty-seven patients (58.2 %) achieved a SVR. Nine patients (9.2%) were diagnosed with EV post-treatment. The adjusted hazard ratios (HR) of the occurrence of EV in patients without SVR and alcohol related were 10.3 (95% confidence interval [CI]: 1.10 -94.9, P = 0.041) and 11.5 (95% CI: 1.49 -88.71, P = 0.019), respectively. The cumulative incidence of EV was significantly higher in patients without SVR (5-year cumulative incidence: 22.4%, 95% CI: 4.9-40.0%) compare to the patients with SVR (5-year cumulative incidence: 3.9%, 95% CI: 0-9%). Conclusions: In cirrhotic HCV-infected patients, SVR is the major predictor in EV development, whereas alcoholism might be a potent predictor of EV progression among these patients.
# 1429 Baseline factors associated with increased sustained virologic response rates in 123 treatment-naive chronic hepatitis C virus genotype 1 patients treated with a shortened 12-week simeprevir plus pegylated interferon and ribavirin regimen: A multivariate analysis Authors:  Table 1. The observed safety profile of SMV + PR was consistent with previous studies. Conclusions: Early on-treatment response patients with IL-28B CC genotype, mild fibrosis (F0/F1), and lower baseline HCV RNA levels are more likely to achieve high SVR12 rates with a 12-week SMV + PR regimen. In the non-CC patient population, mild fibrosis and lower baseline HCV RNA levels were associated with SVR on this shortened regimen. Background: Prevalence of chronic hepatitis C (CH-C) infection in Asian patients ranges between 1% and 20%. Treatment regimens for CH-C have a negative impact on patient-reported outcomes (PRO). Our aim was to assess the PRO impact of interferon (IFN)-free ribavirin (RBV)-free regimens in Asian CH-C patients. Methods: PRO data were collected from 12 multinational phase 3 clinical trials (2012-2015) of sofosbuvir (SOF)-based regimens. At baseline, during and post-treatment, patients completed 4 validated PRO questionnaires which were compared across treatments.
Results: Out of 4485 CH-C patients with PROs, 106 were Asian (55.7% male, 69.8% treatment-naïve, 17.0% cirrhotic). Fifteen received IFN-free RBV-free LDV/SOF treatment and 90 received IFN-and/or RBVcontaining SOF-based regimen. The Asian CH-C patients were younger, had lower BMI and rates of psychiatric comorbidities (anxiety, depression, sleep disorders; all P < 0.05). Also, their baseline SF-36 physical functioning scores were lower (by À5.6% on a normalized 0-100% PRO scale, P = 0.001). During treatment, Asian CH-C patients receiving IFN and/or RBV regimens experienced decreased PRO scores (up to À19.6%, P < 0.050) while those receiving LDV/SOF experienced some improvement (+9.0% in general health of SF-36, P = 0.03). After achieving sustained virologic response 12 (SVR-12), PRO scores improved regardless of treatment (up to +9.3%, P = 0.0003). In multivariate analysis, use of LDV/SOF was independently associated with higher PRO scores during and after treatment (betas +15.0% to +29.3%, P < 0.05). Predictors of PRO impairment included depression, type 2 diabetes, and cirrhosis (P < 0.05). Conclusions: The use of IFN-and RBV-free LDV/SOF regimens leads to PRO improvement in Asian patients during treatment and after achieving SVR-12.
Introduction: Daclatasvir (DCV) and asunaprevir (ASV) have both shown good overall safety and antiviral potency in laboratory and early human studies in the hepatitis C virus (HCV) patients, but as main side effects of its therapy there have not been the report of a renal damage and the hyperkalemia. We report three cases in which the HCV patients that Week 2 viral response was associated with SVR in the univariate analysis of the full population (odds ratio 2.52 [1.13, 5.60], P = 0.0235), but not in the multivariate analysis (odds ratio 1.92 [0.70, 5.29], P = 0.2068). Similar results were found for the association of Week 2 viral response with SVR in the non-CC population and with relapse in both populations analysed. HCV genotype subtype, race, sex and baseline BMI were not associated with SVR in either the full or non-CC patient populations.
presented hyperkalemia after DCV, ASV therapy introduction relatively early this time. Case Report: Case 1: A 76-year-old female with HCV genotype 1b infection cirrhosis and a null response to pegylated interferon-α and complicated with hypertension and diabetes mellitus, started DCV, ASV therapy. A slight renal function disorder and hyperkalemia (5.6 mEq/L) developed after start of therapy three weeks later. Case 2: A 69-year-old female treatment-naïve with HCV genotype 1b cirrhosis complicated with hypertension and diabetes mellitus, started DCV, ASV therapy. A slight renal function disorder and hyperkalemia(5.4 mEq/L) developed after start of therapy one week later. Case 3: A 73-year-old male treatment-naïve with chronic hepatitis C genotype 1b complicated with hypertension, started DCV, ASV therapy. He became hyperkalemia(5.8 mEq/ L) without a renal dysfunction from start one week later. All patients improved hyperkalemia by a potassium diet and the diuretic dosage, polystyrene internal use one or two weeks later. As a main side effect of DCV, ASV therapy, ALT increase 17.6%, AST increase 14.1%, headache 12.9%, fever 11.8% are reported. All three cases were complicated with hypertension and took all cases renin angiotensin system repressor. The aldosterone-producing restraint with the adrenal gland with the RAS repressor is considered as the main reason of the hyperkalemia. DCV, ASV might reduce the potassium excretion with the kidney directly or indirectly with RAS repressor, and it is necessary to note not only the liver damage but also the hyperkalemia symptom during DCV, ASV therapy.
# 1457 Prolonged entecavir therapy improves liver fibrosis estimated by aspartate aminotransferase-to-platelet ratio index in majority of naive patients with a partial virological In a single center cohort study, we retrospectively investigated the longterm changes in liver fibrosis of entecavir treatment for more than 48 weeks in 284 nucleos(t)ide-naïve CHB patients, particularly those with partial virological response (PVR). Serial changes of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) were analyzed using a linear mixed model. Results and Discussion: Seventy-one of 284 (25%) nucleos(t)ide-naïve patients without pretreatment cirrhosis had a detectable HBV DNA at week 48 (PVR). The mean follow-up duration after PVR was 35.0 ± 23.8 months. During prolonged entecavir therapy, 47 (66.2%) patients achieved virological response, and 5 (7.0%) developed genotypic resistance to entecavir. After excluding patients with entecavir resistance (n = 5), who switched to tenofovir due to insufficient virologic suppression (n = 4), and who had been followed up less than 1 year after PVR (n = 8), we finally analyzed non-invasive fibrosis tests of 54 patients. After considering age and gender as fixed effects, APRI values improved significantly with prolonged entecavir treatment (coefficient À0.15, P < 0.0001 Objective: Combination Hepatitis B Immune Globulin (HBIG) and the nucleoside analog prophylaxis has become the standard of care for the prevention of HBV recurrence after liver transplantation for HBV-related diseases. However, HBIG is costly and inconvenient to the patients. In this prospective, randomized, single-center study, we aimed to evaluated the efficacy of a new hepatitis B prophylaxis regimen. Methods: A total of 46 consecutive chronic hepatitis B patients transplanted were included in this study. All patients received the long-term treatment with Entecavir. Control group (30 patients) received combination therapy with long-term low-dose intramuscular HBIG while experimental group (16 patients) received a short-term high-dose intravenous HBIG three to four times within one month after liver transplantation based on HBV DNA level. No HBIG was administered after one month of combination treatment in experimental group which received a subsequent Entecavir monotherapy. Viral load and liver function were detected at regular intervals during follow-up. The detection threshold for the HBV DNA was 100 IU/mL. Hepatitis B recurrence was defined as HBV DNA > 1000 IU/mL during follow-up beyond one month after transplant. Results: There were 17 cases with HBV DNA positive before liver transplantation in control group while 8 cases in experimental group. All patients were alive with a good liver function within 6-12 months in the follow-up after transplantation. There was no HBV recurrence during the follow-up time. Conclusion: HBIG cessation 1 month after liver transplantation with subsequent entecavir monotherapy provides an effective prophylaxis against HBV recurrence compared with long-term HBIG therapy.
# 1476 Aspartate aminotransferase-to-platelet ratio index and sustained virologic response are associated with occurrence of hepatocellular carcinoma among hepatitis C cirrhotic patients receiving pegylated interferon plus ribavirin Authors: SZ-TSAN WANG [1]; KHAI-JING NG [1]; CHIH-WEI TSENG [1,2]; KUO-CHIH TSENG [1,2] Affiliations: [1]Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan [2]School of Medicine, Tzu Chi University, Hualien, Taiwan Background and Aims: The aim of this study was to evaluate the clinically significant predictors for hepatocellular carcinoma (HCC) development among hepatitis C virus (HCV) cirrhotic patients receiving combination therapy. Methods: One hundred and five compensated cirrhosis patients who received pegylated interferon (peg-IFN)plus ribavirin between January 2005 and December 2011 were enrolled. All the patients were examined with abdominal sonography and liver biochemistry at baseline, the end of treatment, and every 3-6 months post-treatment. The occurrence of HCC was evaluated every 3-6 months post-treatment. Results: A total of 105 patients were enrolled (mean age 58.3 ± 10.4 years).The average follow-up time for each patient was 4.38 y (SD 1.73 years; range 1.13-9.27 years). Fifteen(14.3%) patients developed HCC during 463 personyears of follow up. Thirteen of them had high baseline aspartate aminotransferase to platelet ratio index (APRI) (i.e., an APRI > 2.0). Multivariate analysis showed that those without sustained virologic response (SVR) (HR 5.795; 95% CI 1.370-24.5; P = 0.017) and high APRI (HR 5.548; 95% ; P = 0.029)had a significantly higher risk of HCC occurrence. The cumulative incidence of HCC was significantly higher (P = 0.009) in patients without SVR (3-year cumulative incidence 21.4%; 95% CI 7.4-35.5%; 5-year cumulative incidence 31.1%; 95% CI 11.2-51.1%) compared to those with SVR (3-and 5-year cumulative incidence 6.2%; 95% CI 0-1.3%). Further, the cumulative incidence of HCC was significantly higher (P = 0.006) in patients with high APRI (3-year cumulative incidence 21.8%; 95% CI 8.2%-35.3%; 5-year cumulative incidence 30.5%, 95% CI 11.8-49.3%) compared to those with low APRI (3-and 5-year cumulative incidence 4.2%, 95% CI 0-1.0%). Conclusions: In HCV-infected cirrhotic patients who received combination therapy, APRI and SVR are two major predictors of HCC development. Results: In 177 HBeAg-positive patients, the cumulative rates of HBsAg loss in years 3, 5 and 8 were 5.6%, 11.7% and 19.2%, respectively, after stopping NA treatment. Cox regression analysis showed that old age, lower baseline HBV DNA and end-of-treatment qHBsAg were independent predictors for HBsAg loss. In 308 HBeAg-negative patients, the cumulative rates of HBsAg loss in years 3, 5 and 8 were 14.5%, 26.8% and 44% respectively, after stopping NA treatment. Cox regression analysis showed that HBV genotype C and lower end-of-treatment qHBsAg levels were independent predictors for HBsAg loss. For all patients, the cumulative rates of HBsAg loss in patients who had end-of-treatment qHBsAg < 100, 100-300, 300-1000, > 1000 IU/mL in year 8 were 76.8%, 58%, 25.4% and 7.2% respectively. For all patients, the cumulative rates of new HCC development in year 10 (follow-up period included re-treatment duration) in non-cirrhotic and cirrhotic patients were 2.3% and 32.5% respectively. Cox regression analysis showed that old age, cirrhosis and longer treatment duration were independent predictors for new HCC development. The end-of-treatment qHBsAg levels or HBsAg loss after stopping NA treatment was not a significant factor for HCC development.

Conclusions:
The end-of-treatment qHBsAg was a useful predictor for HBsAg loss after stopping lamivudine and entecavir treatment. Pakistan carries one of the world's highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas. Depression is among the most common chronic illnesses. Prevalence of depressive disorders is 34% in Pakistan. Depression is serious side effect of combination interferon and ribavirin therapy which may leads to suicide attempts, timely diagnosis and treatment can prevent this problem. This prompted me to collect data representing our patients on interferon and ribavirin, so as to give a better understanding of the problem and improve the quality of life. Design: Cross-sectional study in 245 patients attending Gastroenterology out-patient department. Patients aged > 18 years of either gender taking combination interferon and ribavirin for Hepatitis C treatment were included in this study. Patients with known psychiatric illnesses or taking antidepressant medicines were excluded from the study. Patients were asked to fill the Siddiqui Shah Depression Scale (SSDS) questionnaire, (In National Language of Pakistan). Patients were categorized as follows according to the number of points they scored in SSDS: < 26 No depression ≥ 26 to 36 Mild depression ≥ 37 to 49 Moderate depression ≥ 50 Severe depression Result: Gender distribution shows predominance of male 59.2%. Average age was 36.4 (±8.8) years. Out of 245 cases, depression was seen in 50 patients (20.4%). In 50 depressed patients, 58% patients had mild symptoms, 32% had moderate and 10% had severe depressive symptoms. Proportion of depression was high in females 22% as compare to 19.3% males. Depression was highest in age between 21 and 40 years; average age was 27.9 ± 9.9 years. Conclusion: Depression is a major factor leading to non-compliance with treatment. Prompt diagnosis and treatment of depression using antidepressant therapy can be safely and effectively used not only to treat depression but also to keep patients compliant to antiviral treatment of chronic hepatitis C.
# 1534 Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy Authors: JI-WEI LIN [1]; MING-LING CHANG [1]; CHAO-WEI HSU [1]; YI-CHENG CHEN [1]; KUNG-HAO LIANG [1]; YA-HUI HUANG [1]; CHEN-CHUN LIN [1]; CHAU-TING YEH [1,2] Affiliations: [1]Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan [2]Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan Background: Acute hepatitis C exacerbations could occur in cancer patients carrying HCV when receiving systemic chemotherapy. No study has been conducted illustrating hepatitis C exacerbation in advanced HCC patients receiving systemic chemotherapy. Aim: Report and analyze clinical factors related to hepatitis C flares in HCV-related HCC patients receiving chemotherapy. Methods: Forty eight patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5-fluorouracil, cisplatin, and mitoxantrone (FMP) from 2008 to 2014 were retrospectively analyzed. Results: Nine patients developed acute hepatitis exacerbations defined by HCV-RNA level increased ≧ 10-fold and alanine transaminase (ALT) level increased fivefold or more of the upper normal limit. Three patterns of clinical courses were observed including single exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Prior to chemotherapy, patients with subsequent acute exacerbations were less likely to have ascites (11.1% vs 53.8%; P = 0.028) and harboring a lower baseline ALT (44.1 ± 28.5 U/L vs 72.6 ± 19.2 U/L; P = 0.007). Univariate analysis revealed unfavorable prognostic factors as ECOG stage > 0 (P = 0.034), presence of ascites (P = 0.002), and higher bilirubin level (P < 0.001). Interestingly, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 versus 5.4 months). Conclusions: Patients with lower baseline ALT and/or absence of ascites had a higher risk of hepatitis C exacerbation when receiving systemic chemotherapy. The hepatitis flares could lead to liver failure but were associated with a better overall survival. Introduction: Adverse effects affecting kidney consist of a decrease of glomerular filtration rate and/or a proximal renal tubular dysfunction. Confirmed hypophosphatemia is one of the indications for tubular function abnormality; however, few data are available on the prevalence of hypophosphatemia in chronic hepatitis B virus infection (CHB) with nucleos(t)ide analogs (NAs). Patients and Methods: Seven hundred and seventeen patients were undergoing NA mono-therapy (57 lamivudine, 225 adefovir, 159 telbivudine, and 276 entecavir) for more than 48 months, while 293 patients were not treated by any NAs. Hypophosphatemia was defined as serum phosphate < 0.8 mmol/L. Chi-squared test and univariate and multivariate logistic regression analyses were performed with the SPSS software. Results: Among the 1010 patients analyzed, 78% were men, the mean age was 42 ± 14 years, the average treatment time was 54 ± 19 weeks, the mean serum creatinine level was 0.94 ± 0.20 mg/dL, the estimated glomerular filtration rate (eGFR) (CKD-EPI) was 97.6 ± 17.2. Prevalence of hypophosphatemia in lamivudine, adefovir, telbivudine, entecavir, and NA-naïve patients was 3.5%, 17.8%, 2.5%, 4.3%, and 2.4% respectively. The chi-squared test showed that the difference among the hypophosphatemia rates among the five groups was statistically significant (χ 2 = 62.904, P < 0.001). In a multivariate analysis (P, odds ratio, 95%

# 1548 Prevalence of hypophosphatemia in chronic hepatitis B virus infection with nucleos(t) ide analogs: A large sample cross-sectional study in China
confidence interval), the independent predictors of hypophosphatemia were adefovir use (vs NA naïve, P = 0.003, 3.972, 1.598-9.874), eGFR < 60 (vs eGFR ≥ 90, P = 0.02, 6.961, 1. Introduction: Creatine kinase (CK) elevations is the most common side effect resulting from telbivudine, while hyperlactatemia or lactic acidosis is rare but fatal. Here, we report six cases of hyperlactatemia/lactic acidosis caused by telbivudine 600 mg/day regularly during the treatment for chronic hepatitis B (CHB). The clinical features of the six patients were summarized so as to make diagnosis and appropriate therapy for the cases.
Cases Report: From January 2010 to May 2015, the six cases are diagnosed in the Third Affiliated Hospital of Sun Yat-Sen University, China. The six patients are all male. The mean age was 28 ± 6.5 years, and the average treatment time was 7.3 ± 3.1 months. The clinical manifestations of these patients include muscle pain and weakness, anorexia, nausea, vomiting, and mild palpitations. The mean lactate (normal range 0-1-.8 mmol/L), CK (normal range 24-184 U/L), myoglobin (MGB, normal range 0-70 μg/L), and lactate dehydrogenase (LDH, normal range 71-231 U/L) were 8. 1 ± 4.2, 1695 ± 562, 378 ± 312, and 593 ± 494, respectively  Background/Aims: Since 2011, combinations of non-structural 3/4 protease inhibitors, telaprevir or simeprevir, with ribavirin and peginterferon have been available in Japan as standard of care for patients with hepatitis C virus genotype 1. We aimed to compare clinical and adverse effects of these inhibitors-based therapies. Methods: Fifty-four patients were treated with 2250 or 1500 mg/day of telaprevir (T-group)and 31 with 100 mg/day of simeprevir (S-group),with combinations of ribavirin and peginterferonα-2a or peginterferon-α-2b for 24 weeks. Protease inhibitors were given for the initial 12 weeks. Doses of these drugs were modified by attending physicians. Clinical and laboratory data were monitored throughout and at 6 months after the treatment. Results: Mean age was 3.1 years old, and liver fibrosis was advanced in the S-group than in the T-group. Seven patients from the T-group and two from the S-group withdrew from the protocol because of adverse events. Forty-three of T-group (79.6%) and 24 of S-group patients (77.4%) achieved sustained virologic response (SVR). Two of four patients in the T-group and one of five in the S-group who were non-SVR had viral breakthrough. Adverse events such as skin rash, appetite loss, and nausea were more severe in the T-group than in the Sgroup. Elevations in serum creatinine and uric acid were seen in the Tgroup, and the rise in serum bilirubin and alkaline phosphatase was seen only in the S-group, which all returned to normal after stopping protease inhibitors. Conclusion: Telaprevir-based and simeprevir-based triple therapy had comparably high SVR rates when the treatment was completed. But severe adverse events limited the effect of treatment in telaprevir-based therapy.
# 1654 Comparison of continuing or modification telbivudine treatment on estimated glomerular filtration rate in patients with chronic hepatitis B-4-year real-word study Authors: MING-WUN WONG [4]; MING-JEN CHEN [1,2,3]; TSANG-EN WANG [1][2][3]; CHENG-HSIN CHU [1][2][3]; SHOU-CHUAN SHIH [1][2][3]; MING-JONG BAIR [3][4][5][6] Affiliations: [1] Background: Telbivudine therapy resulted in improved estimated glomerular filtration rate (eGFR), while other nucleos(t)ide analogs (NUCs) were associated with decreased or stationary eGFR. We do not know the outcome of eGFR in patients with a modification during the telbivudine treatment. Aims: The aim of this real-world observation is to compare continuing or modification treatment of telbivudine on eGFR at the fourth year. Methods: The treatment was according to the Taiwan National Health Insurance clinical practice. Renal functions (eGFR) were recorded at the beginning, treatment modification, and the fourth year on Modification of Diet on Renal Disease calculation. Fifteen patients continued the medication at year 4 without evidence of resistance, while 19 patients were added on or shifted to other NUCs when resistance appeared. Results: At the end of the fourth year, the rates of renal function improved (> 10% increasing eGFR) and were higher at 73.4% in the continue group than at 31.6% in the modification group (P = 0.016). Among the patients who received telbivudine without evidence of resistance, eGFR improved in the checking point and at the fourth year. If there was a treatment modification with adding on or switching from telbivudine, eGFR did not change significantly in the checking point and the fourth year. Detailed data were listed in Table 1. Conclusions: There was no eGFR improvement at the checking point due to resistance existence; the eGFR improvement may relate to treatment and virologic response. When the resistance was overcome by adding on or switching from telbivudine, the eGFR cannot maintain the improvement and even declines. Introduction: Dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome. It is the most frequent arbovirus disease in the world and the most important one in terms of morbidity and mortality. With rising disease burden, atypical manifestations have increased as well, which are missed most often due to lack of awareness. We present one atypical dengue infection with severe hepatitis, acalculous cholecystitis, and normal platelet count. Case Report: A 19-year-old Bangladeshi student without any past history was admitted to ward due to fever, nausea ,vomiting ,jaundice, and epigastralgia for 1 week. The patient denied any drug or alcohol history .Generally, he is jaundiced and lethargic. His blood test results were as follows: aspartate aminotransferase ( , and leptospirosis IgM (À). Abdomen ultrasound was done with acalculous cholecystitis and bilateral pleural effusion. During hospitalization, blood investigation of ANA, C-ANCA, and P-ANCA, anti-mitochondrial antibodies, anti-HIV, and blood film for malarial antigen showed negative results. On day 3 of admission, dengue blood tests were taken: dengue NS-1 Ag (À), dengue IgM (+), and dengue IgG (À). Adequate intravenous normal saline hydration fluid replacement and prophylactic antibiotics were given. He was hospitalized for 13 days and discharged. One week later, he was followed up in a clinic, and his blood test results were as follows: AST 57 U/L, ALT 138 U/L, Bil(T) 45.7 μmol/L, Bil(D) 35.8 μmol/L, INR 1.23, PT 14.7 s, APTT 31 s, platelet 452 000 μL. This patient had recovered uneventfully with great improvement. Discussion: The most common dengue fever symptoms are fever, myalgia, headache, rash, arthralgia, and epigastralgia. Rare manifestations are severe hepatitis, hepatic failure, dengue encephalitis, renal failure, and acalculous cholecystitis. The exact pathogenesis of dengue hepatitis is unknown .It could be either virus direct cytotoxicity to hepatocytes or its immune-mediated injury leading to stimulating apoptosis and microvesicular steatosis and to severe dengue hepatitis. The elevation in the level of AST enzyme is normally greater than the elevation in the level of ALT in dengue patients during the first week of infection, and this is an uncommon phenomenon in patients with hepatitis A, B, or C. Dengue-related acalculous cholecystitis resolves spontaneously with supportive care in majority of cases Conclusion: Clinical doctors should be alert to detect and manage the atypical manifestations of dengue fever. Clinical vigilance about these presentations is vital for dengue early treatment.

Reference:
#  Introduction: Hepatitis B infection is a major public health problem in the Philippines. Although hepatitis B virus (HBV) vaccination has been started in our country for more than two decades, there are no published data regarding the hepatitis B surface antigen (HBsAg) prevalence and immunity level among children. Materials and Methods: We tested for HBsAg on serum samples from children aged 4-6 years. HBsAg-negative samples were tested for total hepatitis B core antibody (anti-HBc). All HBsAg-negative and anti-HBc-negative samples were tested for hepatitis B surface antibody (anti-HBs). Results were compared with data from a study conducted in 1991. Results: A total of 454 randomly selected children were tested. HBsAg prevalence was 0.22% (1/454) among the total population and 0.3% (1/365) among the fully immunized children. Four (1.1%) were reactive to total anti-HBc, indicative of post hepatitis B infection. There was a statistically significant decrease in HBV infection from 131/532 (24.6%) to 1/454 (0.22%), P-value 0.0001, when the current study was compared to the 1991 study. Detectable anti-HBs of 176/365 (48%) showed a decrease in the seropositivity when compared to 182/214 (85%) in 1991, P-value 0.0001. Conclusion: Hepatitis B virus vaccination resulted in a significant decrease in HBsAg prevalence. A significant portion of fully immunized children had no protective anti-HBs but were not infected either. Keywords: Asia, children, HBsAg, prevalence, the Philippines # 1965 Clinical chronic hepatitis C: peginterferon I ± 2a/ribavirin/simeprevir combined therapy: Device of individual medical treatment for elderly patients, including interferon I2 for carcinogenic prevention Authors: MASAHIKO SUGANO; TAKAKO MATSUNO Affiliation: Sugano Internal Medicine Clinic, Himeji, Japan Aim: Despite the high sustained virologic response (SVR) rate in interferon (IFN)-free therapy, IFN was also used by priority for carcinogenic prevention. PegIFN-α/REV/simeprevir with an excellent therapeutic effect is employed as the main treatment for elderly patients, because the side effects are equivalent to those of pegIFN-α/REV. IFN-β preceding prescription is also considered as an independent medical treatment. We investigated the safety and efficacy of these treatments. Method: Between April 2007 andJanuary 2015, 195 patients were introduced to peg-IFN-α. Twenty-one underwent peg-IFN-α/RBV/simeprevir (≥ 60 years old: 13), and 51 underwent peg-IFN-α2a/REB (≥ 60 years old: 30, ≤ 59 years old: 21); we compared each groups. Among peg-IFN-α2a, Gr1, and IFN-β preceding prescription, 47 (60.3 years old, M:F = 21:26) and 44 patients without 23:21) are also compared. Side effects like fatigue, alopecia, appetite loss, and depression were scored (0-3). Result: Peg-IFN-α/REV/ simeprevir (58.8, 10:11) had HCV-RNA 6.0 log IU/mL and alanine aminotransferase (ALT) 57.3 IU/L. The virus-negative rate was 21.4% (2 weeks), 60.0 (4 weeks), 78.9 (8 weeks), 88.9 (12 weeks), and 91.7 (end treatment response [ETR]), and the SVR12 was 83.3% (5/6). Peg-IFN-α2a/REV (≤ 59/ ≥ 60 years old) showed pretreatment HCV-RNA (6.2/6.0), ALT (63/49), and SVR (47. 6/43.3).  (16), mental disease (7), IFN-rebound therapy (7), ETR (IFN-β: 71.9/without: 69.4), and SVR (47.1/44.7). Side effect scores were as follows: fatigue 1.02/0.70, appetite loss 0.70/0.61, alopecia 0.57/045, and depression 0.55/0.32. Although the IFN-β group has bad condition before treatment, the SVR rate excels in the usual group. Conclusion: Hepatitis C patients are aged and had carcinogenic prevention emphasized. Simeprevir/peg-IFN-α/REB has good effectiveness and no increasing side effects. Elderly patients can be also introduced to individual treatment including IFN-β. Case Description (Methods and Results): A 54-year-old man acquired HIV infection 17 years ago. He was given combivir and a protease inhibitor. He achieved satisfactory HIV viral load suppression with lamivudine-containing antiretroviral therapy (ART). HBV co-infection was diagnosed 10 years later. The addition of adefovir demonstrated slow HBV viral load reduction (4 log) with virological breakthrough 15 months later. HBV viral resistance testing showed rtL80V, rtL180M, and rtM204V/I mutations. In concordance with more recent HIV therapeutic recommendations, the regime was changed to Truvada-containing ART. There was again HBV virological breakthrough 42 months post therapy. A similar partial viral suppression was noted with the addition of entecavir (ETV). Pegylated interferon would be the sole remaining therapeutic option. Discussion: Compliance may not be the issue as HIV remained well suppressed, prompting a search for alternative reasons for virological breakthrough. Kitrinos et al. reported tenofovir monotherapy should be effective for at least 6 years without significant mutation selection. This regimen is also reported to be the best combination for patients with lamivudine-resistant hepatitis B. ETV resistance requires at least three mutations: rtL180M + rtM204V and either rtT184G/S or rtS202I/G or rtM250V. This patient has only the rtL180M + rtM204V mutation. Emtricitabine is also reported to have anti-HBV properties but only in the absence of M184V HIV mutation. The "recalcitrant" HBV in this case study suggests the possibility of other undiscovered pathways.
# 1991 Applying non-invasive assessment of liver fibrosis in chronic hepatitis B patients with equivocal indication for antiviral therapy Authors: LU-HAN FANG [1]; CHENG-HAO TSENG [1]; YAO-CHUN HSU [1]; JAW-TOWN LIN [2]; CHI-YANG CHANG [1]; CHUN-YING WU [3] Affiliations: [1]E-Da Hospital and I-Shou University, Kaohsiung, Taiwan [2]Fu Jen Catholic University, New Taipei City, Taiwan [3]Taichung Veterans General Hospital, Taichung, Taiwan Objective: This study aims to evaluate whether blood-based biomarkers and acoustic radiation force impulse (ARFI) could spare liver biopsy to guide treatment in chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy. Study Design: This is a cross-sectional analysis of prospective biochemical, sonographical, and histological data. Methods: This study enrolled 101 CHB patients with viral DNA > 2000 IU/mL, but alanine aminotransferase (ALT) was mildly elevated between onefold and twofold above the upper normal limit (Table 1). Those with cirrhosis, hepatic decompensation, and malignant disease were excluded. All participants underwent liver biopsy and ARFI. The performance of ARFI, aspartate aminotransferase (AST) to platelet ratio index (APRI), and fibrosis-4 (FIB-4) score to identify patients with significant liver fibrosis was analyzed. Results: Liver fibrosis was Metavir F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients. The stage was correlated with ARFI (ρ, 0.38; P = 0.0001) (Fig. 1), APRI (ρ, 0.25; P = 0.012), and FIB-4 (ρ, 0.28; P = 0.004). The C statistics of ARFI, APRI, and FIB-4 for fibrosis stage ≧ 2 were 0.70 (95% confidence interval [CI], 0.59-0.80) (Fig. 2), 0.62 (95% CI, 0.51-0.73) (Fig. 3), and 0.64 (0.53-0.75) (Fig. 4), respectively. Cut-off values for 95% sensitivity and 95% specificity to predict significant liver fibrosis were 0.97 and 1.36 m/s for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. A combination of these cut-off points could spare a total of 44 patients (43.6%) from liver biopsy. Conclusions: A combination of ARFI, APRI, and FIB-4 can spare liver biopsy in approximately 40% of noncirrhotic CHB patients with equivocal indication for antiviral treatment.      1970-1983. In the age group of 60-69, the anti-HCV-positive rate was 7.9% in birth_cohort 1920-1929 and 8.1% in birth_cohort 1930-1939, while it was 5.9% in birth_cohort 1940-1949. For both HBsAg and anti-HCV, there were trends that seroprevalence decreased in the younger cohort (Fig. 1). Multiple logistic regression showed that male gender, younger age, and earlier birth year were associated with positive HBsAg. Older age and earlier birth year were associated with positive anti-HCV. Conclusions: The prevalence of HBsAg and anti-HCV was influenced by birth cohort effect.  Background: Egypt has the highest prevalence of hepatitis C virus (HCV) in the world (~14.7%), of which 10-15% will advance to cirrhosis within 20 years with growing incidence of hepatocellular carcinoma (HCC). Early detection is critical for favorable clinical outcome. No single reliable noninvasive marker is available. Beta-2 microglobulin (B2M), a nonglycosylated peptide, part of human leukocyte antigen class I complex, was reported to be elevated in chronic HCV infection. Determining its clinical utility as a marker for disease progression in Egyptian patients with HCV-related liver diseases was the aim of the study. Patients and Methods: This is an analytical cross-sectional study including 92 subjects divided into four equal groups: group 1, chronic HCV; group 2, HCV cirrhotics; group 3, HCC on top of HCV; group 4, healthy controls. History taking, clinical examination, routine labs, and abdominal ultrasound were done to all patients. Polymerase chain reaction (PCR) and Metavir score for group 1 and triphasic computed tomography of the abdomen and αfetoprotein (AFP) for group 3 were identified. B2M was measured in serum by a fully automated IMX system. Results: Serum B2M levels were higher in cirrhosis and HCC groups than in the HCV group and controls (P < 0.01). B2M correlated directly with alkaline, total and direct bilirubin, and international normalized ratio (P < 0.05) and inversely with albumin, total proteins, hemoglobin, WBCS values (P < 0.05). The best B2M cutoff for HCV diagnosis was 2.6, sensitivity 100%, specificity 92%, positive predictive value (PPV) 97%, and negative predictive value (NPV) 100%. The best cut-off for cirrhosis was 4.9, sensitivity 74%, and specificity 74%. The best B2M cut-off for HCC diagnosis was 4.55, sensitivity 74%, specificity 62%, PPV 39.5%, and NPV 87.8% (P < 0.01). Area under the curve for HCC diagnosis reached 0.93 upon B2M and AFP combination. Conclusion: The serum B2M level was elevated in HCV-related chronic liver diseases and may be used as a marker for HCV disease progression.
Keywords: B2M, HCC, HCV, marker, progression, serum.   Table 1. The use of the reminder system before chemotherapy had increased the screening rate from less than 70% to 89% for HBsAg and from 0% to 84% for anti-HBc. Conclusions: This study demonstrates the feasibility of implementing a reminder system to increase the screening rate of HBV infection. The system allowed physicians to identify patients at a higher risk for HBV reactivation and to provide prophylactic measures according to current guidelines. The rate of antiviral prophylaxis and HBV reactivation will be evaluated in further study. # 2143 Distinct viral evolution and quasispecies dynamics between hepatitis B e antigen seroconverters and non-seroconverters in response to interferon-based therapy Authors: HUNG-CHIH YANG [1,3]; SU-RU LIN [1]; CHUN-JEN LIU [2,3]; CHENG-YUAN PENG [4]; TAI-CHUNG TSENG [5]; TUNG-HUNG SU [3]; PEI-JER CHEN [2,3]; JIA-HORNG KAO [2,3] Affiliations: [1] (Fig. 1). Interestingly, patients who underwent HBeAg seroconversion but remained highly viremic exhibited low viral genetic diversity. Furthermore, the genetic diversity was negatively correlated with levels of HBV viral load (r = À0.608, P < 0.001) and HBsAg (r = À0.709, P < 0.001). Additionally, the viral evolution rate of HBeAg seroconverters with low viremia was faster than that in patients without HBeAg seroconversion. The number of nucleotides with a significant frequency change, defined as greater than 50%, was more in patients with HBeAg seroconversion. We also identified certain amino acid changes that were associated with HBeAg seroconversion. Finally, the network analysis of HBV evolution revealed distinct evolution patterns between HBeAg seroconverters and non-seroconverters. Background/Aim: The all-oral, ribavirin-free, direct-acting antiviral regimens are the current trend of therapy in patients with chronic hepatitis C virus (HCV) infection. The fixed-dose combination of daclatasvir (a pangenotypic NS5A inhibitor) and asunaprevir (an NS3 protease inhibitor) achieves excellent sustained virologic response in the clinical trials. This study is to investigate the incidence of resistance-associated variant (RAV) and the efficacy of this regimen in the real world. Methods: There were 34 patients of chronic hepatitis C (CHC), genotype 1b, who received an RAV test. Among those with no RAV, 18 patients received a 24-week, twice-daily, fixed-dose combination of daclatasvir (30 mg) and asunaprevir (200 mg) and had been treated for greater than 4 weeks. Treatment was discontinued in cases of virologic breakthrough, defined as a confirmed increase in HCV-RNA of 1 log 10 IU/mL or greater from nadir or confirmed increase in HCV-RNA to greater than or equal to the assay lower limit of quantitation (LLOQ; 15 IU/mL) after a previous decline to less than the LLOQ. The presence of cirrhosis was established by a liver biopsy or a FibroScan value greater than 12.6 kPa within 1 year. HCV-RNA was quantified using the Roche HCV COBAS TaqMan Test v2.0 (LLOQ 15 IU/mL; limit of detection, 10 IU/mL). Genotype and subtype were determined by the VERSANT HCV genotype 2.0 line probe assay. Resistance testing was performed by population-based sequencing (sensitivity, 25%) of NS3, NS5A, and NS5B at baseline and on samples with HCV-RNA of 1000 IU/mL or greater. Statistics were assessed by SPSS, version 16.0. Results: The 34 patients were 62.6 ± 9.8 years old and included 15 males (44.1%), 26 experienced (66.5%), and 24 cirrhotics (70.6%). Six (17.6%) of them had RAV. Those with RAV were older (median: 75.4 vs 60.0 years, P = 0.002), were experienced (100% vs 71.4%, P = 0.297), and had greater amount of HCV-RNA (median of log 10 : 7.21 vs 6.18, P = 0.003). Age was the only associated factor of RAV by multivariate logistic regression (P = 0.013). Among the 28 patients with no RAV, 18 patients had received the combination therapy for longer than 4 weeks. They were 61.9 ± 7.6 years old, and 9 (50%) were male. Thirteen (72.2%) were treatment experienced, and 13 (72.2%) were cirrhotics and had a log 10   Background and Aim: The epidemiology of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection in Tainan City, a hyperendemic area of viral hepatitis, is well documented. However, the disease awareness and the linkage to care are still not well known. We aimed to evaluate these two important issues in the Chiku and Chiangchun townships. Method: We conducted a hepatitis screening program from Aug 2014 to May 2015 in two remote villages of Southern Taiwan. All participants received questionnaire evaluation, blood tests including alanine aminotransferase, aspartate aminotransferase, hepatitis B surface antigen (HBsAg), and anti-HCV Ab (antibody). The questionnaire evaluation form was composed of HBV/HCV awareness, testing, disease concept, and linkage to care.
Result: There were 605 residents who participated in the program. The HBsAg positivity is 12.7% (77/605). Among HBsAg + subjects, HBV viremia was noted in 58/77 (75.3%). Among the HBsAg subjects, the percentage of HBV DNA > 2000 IU/mL is 32.4% (25/77). The HCV Ab positivity is 17.7% (107/605). The HCV viremia percentage is 51.4% (55/107). The genotype distribution is as follows: G1 + G1a + G1b = 22 (40%), G2 = 32 (58%), and G6 = 1 (2%). Of the 605 patients, 318 (52.6%) were never tested for HBV, and 16 of them are positive for HBsAg. Of the 605 patients, 46.9% once received HBV test before, and 61 patients were HBsAg + before this screening program. Of the 605 patients, 405 (66.9%) are never tested for HCV, of whom 37 are positive of HCV Ab, and 195 (32.2%) once received HCV testing. Among 195 patients who received an HCV test before, 70 patients were infected with HCV Ab+. Among 73 patients who were known for HBV infection, 48 patients were not followed, 7 patients were followed in general practice (GP), and only 18 patients were followed in gastrointestinal (GI)/liver clinics. Among 46 patients who were known for HCV infection, 20 patients were not followed, 5 patients were followed in GP, and 21 patients were followed in GI/liver clinics. Result: Hepatitis B virus and HCV are still important public issues in Tainan city, and further education plans about disease awareness and treatment should be enforced in the future.

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# 1008 Administration of antisense oligodeoxynucleotides to nerve growth factor attenuates inflammation and liver damage in acute liver damage models Authors: BRUCK R; HUBEL E; ZVIBEL I Affiliation: The Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Background/Aims: Nerve growth factor (NGF) has pro-inflammatory effects in lung and skin inflammatory diseases. During liver regeneration, NGF secreted by hepatocytes induces hepatic stellate cell apoptosis. However, NGF involvement in models of liver damage and inflammation has not yet been assessed. We investigated the possible inflammatory effects of NGF on isolated hepatic stellate cells (HSC), as well as the in vivo effect of silencing NGF on acute liver damage and inflammation. Methods: Primary HSC from rats and mice were isolated and cultured for 7 and 14 days to obtain activated and fully activated HSC, respectively. HSC were treated with 100 ng/mL NGF and pro-NGF, and inflammatory cytokine expression was assessed by quantitative reverse transcription-polymerase chain reaction and ELISA. Acute liver damage was induced by two intraperitoneal injections of CCl 4 (1 μL/g body weight) or by bile duct ligation (BDL), and mice received daily treatment with antisense oligodeoxynucleotide to NGF (ODN) (25 mg/kg body weight). Results: Both NGF and pro-NGF induced expression of pro-inflammatory cytokines, tumor necrosis factor (TNF), and interleukin (IL)-6 in activated and fully activated primary rat and murine HSC. Administration of antisense ODN to NGF in the acute CCl 4 and BDL models reduced liver damage, as demonstrated by significantly reduced serum liver enzymes. In addition, antisense ODN to NGF resulted in dramatically reduced (sixfold) hepatic mRNA expression of pro-inflammatory cytokines IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) in the acute CCl 4 acute model. In the BDL-induced acute liver injury, administration of ODN resulted in a twofold reduction in TNF-α, MCP-1, and CXCL1 expression. Conclusions: Silencing NGF may have a beneficial, anti-inflammatory, and protective effect in acute hepatotoxicity models.  2.4-7.19%). Nausea and abdominal pain were the most frequently observed signs and symptoms. Three (33.33%) ATLI patients had severe hepatotoxicity, seven (77.77%) recovered, one (11.11%) failed to respond to treatment with continued elevation of aminotransferases, and one (11.11%) died as a result of ATLI. Conclusion: For this cohort, ATLI incidence was higher compared to data from China and Canada, comparable with Hong Kong and Singapore, but lower than Taiwan. The presence of comorbidities showed a trend of increasing ATLI; however, further analysis only showed those with liver and biliary diseases to be statistically significant. A larger cohort of patients is suggested. Keywords: antituberculosis-induced liver Injury, drug-induced liver injury, tuberculosis.
# 1056 Intrahepatic cholestasis in hyperthyroidism Authors: NATA PRATAMA HARDJO LUGITO; THEO AUDI YANTO; RESA SETIADINATA Affiliation: Internal Medicine Department, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia Introduction: The relation of jaundice to hyperthyroidism can be presented in three clinical possibilities: hyperthyroidism is the underlying cause of jaundice, a chronic liver disease patient liver function deteriorates with deep jaundice, and a hyperthyroidism patient develops jaundice. The mechanism underlying jaundice observed in hyperthyroidism is not clear, but different functional and histological hepatic changes have been reported in patients with hyperthyroidism. Liver function test abnormalities in hyperthyroidism can be mainly divided into two types; hepatocellular pattern and intrahepatic cholestasis pattern. High levels of thyroxine hormones, the hypermetabolic state, thyroid hormones' direct toxic effect on hepatic tissue, and hyperthyroidism medication can cause jaundice in hyperthyroidism patients. Case Description: A 25-year-old female with uncontrolled hyperthyroidism who had intrahepatic cholestasis was examined. Further examinations did not find chronic or acute viral hepatitis, hepatic congestion, hepatic injury, hepatotoxic side effects of anti-thyroid medications propylthiouracil (PTU) as a cause for her intrahepatic cholestasis. After PTU medications, her condition improved, total, direct, and indirect bilirubin of 25.20, 20.10, and 5.10 mg/dL decreased to 13.63, 10.39, and 3.24 mg/dL, respectively.
cross-sectional study, 1000 consecutive subjects appointed at the University Digestive Centre of a Singapore tertiary medical center in 2011 were included (Fig. 1). To identify NAFLD intervention, 238 eligible subjects were reviewed for liver function test performed within 3 months of their liver imaging. Two designated radiologists also reviewed the images to ascertain the presence of NAFLD against standardized, validated criteria. Discrepancies in NAFLD identification between the original and reviewed reports were identified. Independent predictive factors for NAFLD were determined using multiple logistic regression. Results: Of the subjects with NAFLD (original report), 35.3% (n = 41) had no intervention within 3 months. Among the scans reviewed, 11.3% (n = 26) were found to be negative for NAFLD on the original report but positive on review. Significant independent predictive factors of NAFLD are diabetes mellitus (P = 0.046, odds ratio [OR] = 2.416, 95% confidence interval [CI] = 1.017-5.741), and aspartate aminotransferase > 30 U/L (P = 0.047, OR = 2.087, 95% CI = 1.009-4.317). Conclusion: Missed opportunities for early intervention are significant among study subjects. A common criterion is useful in standardizing radiological NAFLD identification. Multivariate analysis allows NAFLD to be predicted by combining various risk factors.
Keywords: diagnosis, imaging, missed opportunities, non-alcoholic fatty liver disease (NAFLD), risk factors of NAFLD. # 1293 Diagnosis and management of peritoneal chylous leakage after liver transplantation Authors: WANG GUO-YING; YANG YANG; CHEN GUI-HUA Affiliation: Liver Transplantation Center of the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Objective: Peritoneal chylous leakage after liver transplantation (LT) is an uncommon complication, and the optimal treatment remains unclear. The aim of this study was to investigate the diagnosis and management of peritoneal chylous leakage after LT in our liver transplant institute. Methods: Between June 2012 and April 2014, 241 patients received LT at our institution. The clinical data of the patients with peritoneal chylous leakage were collected and analyzed retrospectively. The diagnosis of chylous leakage is based on the presence of milky and creamy ascites with a positive result of chylous test. Results: Nineteen patients were diagnosed with peritoneal chylous leakage after LT (mean 10.8 days after LT). The incidence of the chylous leakage after LT was 7.9%. All patients received conservative treatment, which involved the cessation of oral diet, total parenteral nutrition, somatostatin, and passive peritoneal drainage. No patients received laparotomy. One patient, whose peritoneal drainage had been removed, was treated with catheter drainage guiding by ultrasonography. Eighteen patients healed with no further complications. One patient died 44 days after transplantation due to multidrug-resistant Acinetobacter baumannii pneumonia, which was considered unrelated to the formation of chylous leakage because the amount and quality of the drainage decreased gradually and the drain was removed 21 days after LT. Conclusion: Peritoneal chylous leakage after LT is not a rare complication. Combination treatment with total parenteral nutrition and somatostatin is an effective method to therapy peritoneal chylous leakage after LT.
# 1374 Aggravation of liver function of autoimmune hepatitis by artemisia capillaries-Three case reports Authors: RYUSUKE KATO Affiliation: Otaru Kyoukai Hospital, Otaru, Japan Background: Artemisia capillaries (AC) has been used to treat inflammatory and hepatic disorders such as hepatic injury, hepatic fibrosis, and hepatitis. We report on the three cases of patients with autoimmune hepatitis (AIH) to describe the possibility of AC aggravating autoimmune hepatitis. Case Report: Three patients diagnosed with AIH have been treated with predonine. To try to put AIH under more strict control, I prescribed AC to them. Laboratory data got worse after they took AC for about 1 month. Therefore, I stopped prescribing AC. About 2 weeks later, their laboratory date improved. In this period, another drug was prescribed, and the dose of steroid was not changed. And there were no factors of aggravating liver functions. I show the course of liver function as below.  [4]; JT HU [3,5]; SS YANG [3,5] (6) or A(TA) 7 TAA (7) promoter variant, and the coding region for nucleotide mutations (nt)-211 G to A (G71R), nt-686 C to A (P229Q), nt-1091 C to T (P364L), and nt-1456 T to G (Y486D). Results: Two patients were homozygous for the nt-211 G > A mutation, and two patients were heterozygous for the 6/7 promoter genotype and the nt-211 G > A mutation, whereas four patients were with homozygous 7/7 genotype and were diagnosed with Gilbert's syndrome. The percentage of 7/7 genotype patients (50%) was comparable with Caucasian, African, and Indian populations but significantly higher than other Asian countries. We did not identify any Mongolian patient with nt-686 C to A, nt-1091 C to T, or nt-1456 T to G mutations, which are common in Asian countries but not in the Western population. One patient with homozygous nt-211 G > A mutation developed severe indirect hyperbilirubinemia during the initial phase of the combined interferon and ribavirin therapy. Conclusion: The prevalence of UGT1A1 abnormalities in Mongolians are more similar to the Western population than the Asian population, whereas the high prevalence of nt-211 G > A mutation is similar to Asians.
# 1610 An unusual case of hepatitis B flare in a patient with metastatic pheochromocytoma Authors: KALAIYARASI KALIYAPERUMAL; CHARLES VU Affiliation: Tan Tock Seng Hospital, Singapore Background: The exact interplay of endogenous cortisol and hepatitis B reactivation is not entirely understood. The possible postulated mechanisms include a persistent immunocompromised state predisposing to a flare and/or the activation of the glucocorticoid responsive elements in the hepatitis B viral (HBV) genome leading to HBV replication and gene expression. Methodology/Results: We present an interesting case of a 71-year-old man with metastatic pheochromocytoma co-secreting adrenocorticotropic hormone, who presented with a hepatitis B flare. This occurred in the setting of a rising cortisol level and a recent initiation of ketoconazole for chemical adrenalectomy. Entecavir was started for the patient with subsequent normalization of the liver function test. Conclusion: The role of endogenous cortisol excess in the reactivation of hepatitis B is less well understood and studied, compared to exogenous steroid intake. By highlighting this unusual case, we hope to alert physicians to this potential association. Screening for hepatitis B and antiviral therapy may help to prevent a hepatitis B flare and liver decompensation.
# 1618 An unusual case of spontaneous bacterial peritonitis in a patient with peritoneal carcinomatosis Authors: YANG ZJ; KALIYAPERUMAL KK Affiliation: Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore Background/Aim: This study aims to describe a case of spontaneous bacterial peritonitis (SBP) occurring in a patient with malignant ascites from underlying pancreatic adenocarcinoma. Methods: A 57-year-old Indian gentleman, presented to the Emergency Department with new-onset ascites of 1-week duration, loss of weight, and fever. Physical examination revealed tense, tender ascites with no signs of chronic liver disease or heart failure. Abdominal paracentesis done demonstrated yellow and turbid fluid with the following results: a corrected polymorphonuclear cell count of 2430 (74% neutrophils) and a serum ascites albumin gradient of 12 mmol/L. Ascitic fluid gram stain and cultures were negative. Results: A diagnosis of culture-negative SBP was made, and he was started on antibiotics. Fluid cytology showed metastatic adenocarcinoma. A computer tomography scan revealed a pancreatic body mass with hepatic and peritoneal metastases. There was no radiological evidence of cirrhosis, splenomegaly, or varices. He was subsequently referred to medical oncology for chemotherapy. Conclusion: The majority of SBP tends to occur in cirrhotic ascites, but it is rare in malignant ascites. To our knowledge, only a few have been reported in current literature. We chose this case to highlight the unusual presentations of SBP in non-cirrhotic ascites so that physicians will maintain a high index of suspicion for early institution of treatment.
We postulate that lymphatic hypertension from disseminated intraabdominal nodal malignancy may predispose to rupture of smaller lymphatics and showering of incumbent intestinal flora into the ascitic fluid, similar to cirrhotic ascites. However, further studies are needed to evaluate this.
However, the CCl4-induced anorexia and detailed protective mechanisms of the SNS ablation need to be further investigated. Methods: Acute liver injury was induced in mice with and without chemical sympathectomy by a single injection of CCl4. Enteropathy-associated anorexia was assessed. Liver injury and expressions of cytochrome P450 2E1 (CYP2E1), heme oxygenase-1 (HO-1), cytokines, and chemokines in the liver were measured Results and Discussion: Chemical sympathectomy prevented CCl4-induced ileal villous edema-associated anorexia (Fig. 1).
Expressions of CYP2E1, a pro-oxidant, and HO-1, an anti-oxidant, were increased after chemical sympathectomy. Attenuated injury in sympathectomized mice was associated with raised HO-1, not CYP2E1, expression. These results suggest that chemical sympathectomy failed to prevent suicidal degradation of CYP2E1 (Fig. 2). Moreover, chemical sympathectomy modulated the CCl4-induced inflammatory responses within the liver, including interleukin (IL)-1α, IL-10, leptin, tissue inhibitor of metalloproteinase-2, soluble tumor necrosis factor receptor I, granulocyte-macrophage colony-stimulating factor, CCL3, CCL5, CCL9, CCL11, and CXCL11 (Fig. 3). To the best of our knowledge, this is the first demonstration of expression of CCL9, a mouse CC chemokine and strong chemoattractant for bone marrow cells, 1 in the liver. Conclusions: These results indicate SNS ablation prevents enteropathy-related anorexia and acute hepatic injury associated with HO-1 expression in CCl4-treated mice. We also suggest that SNS may be providing a permissive microenvironment affecting expressions of cytokines and chemokines in hepatocytes.
Keywords: carbon tetrachloride, chemokines, cytokines, heme oxygenase-1, sympathetic nervous system. # 1648 Clinical and histological differences between drug-induced autoimmune hepatitis and classical autoimmune hepatitis Authors: DSC KOAY [1]; WQ LEOW [3]; TW CHNG [3]; HL HOO [3]; E SALAZAR [1]; KH LIM [3]; JH NGU [1,2] Affiliations: [1]Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore [2]Duke-NUS Graduate Medical School, Singapore [3]Department of Pathology, Singapore General Hospital, Singapore Background: The exact etiology of autoimmune hepatitis (AIH) is uncertain, but it can be triggered in susceptible persons by drugs. An increasing number of drug-induced AIH (DIAIH) cases were reported, but they remain poorly characterized. We aim to compare the clinical and histological characteristics of DIAIH and classical AIH. Methods: Consecutive cases fulfilling AIH simplified criteria diagnosed between 2008 and 2013 in Singapore General Hospital were included. DIAIH was defined as patients fulfilling standardized diagnostic criteria but also had identifiable drug suspected of triggering AIH. Histology was reviewed by three independent liver pathologists blinded to the cases. Known features of AIH and druginduced liver injury such as plasma cells, rosettes, emperipolesis, inflammation, eosinophils, cholestasis, bile duct damage, and fibrosis staging were assessed for each case. Results: Sixty-two patients were included. Of these, nearly a quarter(24.5%) fulfilled the study definition of DIAIH. Nitrofurantoin was implicated in one case of DIAIH, whereas the rest were associated with traditional Chinese medicine use. Classical AIH patients were more likely to present with advanced fibrosis (Metavir > 2) than DIAIH patients (P = 0.02). Histology features were otherwise not  significantly different between AIH and DIAIH. Clinically, DIAIH patients were more likely to present with severe jaundice (bilirubin > 320) and prolonged prothrombin time > 15 s. DIAIH patients were less likely to require long-term treatment(P = 0.03). Conclusion: Histological features were similar and not helpful in differentiating DIAIH from classical AIH, although DIAIH patients were significantly less likely to present with advanced fibrosis. Clinically, DIAIH patients were significantly more likely to present with liver synthetic dysfunction but less likely to require longterm immunosuppressive treatment.
# 1664 The first-line antiviral agents for viral hepatitis B: A clinical physician's perspective in medical economic at a medical center Authors: TSANG-EN WANG [1,2]; CHIH-JEN CHEN [1]; CHIEN-YUAN HUNG [1]; SI-HSUAN CHEN [1]; CHENG-HSIN CHU [1] Affiliations: [1] Background/Aim: The American Association of the Study of Liver Diseases, European Association of the Study of the Liver, and Asian Pacific Association for the Study of the Liver, and World Health Organization guidelines all recommend initial treatment with entecavir (ETV) or tenofovir (TDF) for chronic hepatitis B patients. TDF and ETV may be similarly effective and safe. However, most economic benefit studies come from insurance and social perspectives. In this report, we like to know laboratory test items and the impact of time costs when clinicians prescribe these drugs in outpatient departments. Methods: Randomly, we selected patients who received a first prescription TDF or ETV in 2014. Patients with malignancy and hospitalization were excluded. The laboratory test items were recorded from last to after-visit date of the clinicians prescribing. We also tried to analyze visit times of patients. Results: Fifty-two patients were included: 30 with ETV and 22 with TDF. All patients had hepatitis B virus DNA, alanine aminotransferase, and aspartate aminotransferase results before taking an antiviral agent. The proportion of creatinine test was 17% versus 68%, and blood urea nitrogen test was 0% versus 32% (ETV vs TDF). The ETV group did not have electrolyte reports. Serum phosphate and urinalysis were checked in 5% and 23% patients with TDF. The time of visits had a great difference that could not be parsed for time cost. Discussion/Conclusion: There were many limitations in this observation. However, clinicians are still concerned about the safety of renal impairment in TDF. Comparing patients with ETV treatment, clinicians did more tests and might take more time to check and explain the data for these patients. This prescription of TDF will have more hidden costs than ETV in clinical practice.
# 1674 Diabetes: Its impact on liver diseases Authors: DEEPAK N AMARAPURKAR; MRUDUL V DHAROD Affiliation: Bombay Hospital and Medical Research Centre, Mumbai, India Korean adults using the Korea National Health and Nutrition Examination Surveys. Methods: Serum 25(OH) D levels were measured and then categorized into deficient (≤ 20 ng/mL), insufficient (> 20-30 ng/mL), and sufficient (≥ 30 ng/mL) groups. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations were defined as > 30 IU/L for men and > 19 IU/L for women. The association between vitamin D level and aminotransferase concentration was tested by chisquared tests and multiple logistic regression analyses. Results: The prevalence of elevated ALT was 25.0%, 24.7%, and 22.6% in deficient, insufficient, and sufficient groups, respectively. The proportions of individuals with elevated AST were 30.0%, 31.5%, and 34.5% in deficient, insufficient, and sufficient groups, respectively. Compared to the deficient group of vitamin D, subjects with higher serum vitamin D levels had significantly lower risks for elevated ALT concentration (insufficient group: adjusted odds ratio [aOR] = 0.87, 95% confidence interval [CI] = 0.79-0.96, sufficient group: aOR = 0.76, 95% CI = 0.62-94) in the high-risk group for liver injury. Conclusions: Higher vitamin D level was significantly associated with the lower risks of elevated ALT concentration in Korea.
# 1986 Gilbert syndrome in an adolescent male with coexisting glucose-6-phosphate dehydrogenase deficiency: A case report Authors: PRINCESS A. GUEVARRA, MD; PATRICIA S. TE, MD Affiliation: Section of Gastroenterology, Chinese General Hospital and Medical Center, Manila, the Philippines Background: Gilbert syndrome is the most prevalent inherited disorder of unconjugated hyperbilirubinemia with reduced expression of promoter glucuronosyltransferase 1 (UGT1A1) gene. In Southeast Asia and Pacific Islands, prevalence is less than 5% of the population. Studies have shown a correlation between Gilbert syndrome and glucose-6-phosphate dehydrogenase (G6PD) deficiency. The presence of a UGT1A1 promoter gene variant is attributed to the development of hyperbilirubinemia in G6PD deficiency. Clinical Description: We present a case of a 16-year-old, male, with jaundice, and diagnosed G6PD deficiency at birth. Interval history was unremarkable. Patient engaged in strenuous sports activity accompanied by episodes of missed meals. Subsequently, he developed jaundice, tea-colored urine, fatigue, and anorexia. He had no history of alcohol or drug intake, fever, and concurrent illness. On examination, he showed hepatomegaly without other stigmata of liver disease. Liver biochemistry revealed elevated serum total bilirubin (335 μmol/L) with a predominance of unconjugated bilirubin (263 μmol/L). Hepatobiliary tree ultrasound, viral hepatitis markers, complete blood count, and liver function tests were unremarkable: serum glutamic pyruvic transaminase (70.8 U/L), alkaline phosphatase (71 IU/L), albumin (4.5 g/dL), prothrombin time (13.5 s, international normalized ratio 0.98). UGT1A1 gene mutation test was not done due to unavailability in the country. Consequently, diagnosis by exclusion of Gilbert syndrome was made. Patient was managed conservatively and improved. Conclusion: In a patient with G6PD deficiency with jaundice and unconjugated hyperbilirubinemia, a diagnosis of Gilbert syndrome is highly considered. The associated co-inheritance of a variant promoter UGT1A1 gene is strongly correlated with coexisting G6PD deficiency proven in studies. Identification of this condition will warrant directed diagnostic approach and management. There have been only a few case reports published linking sulfonylureas, in particular, gliclazide, to acute hepatitis. We describe a case where an 80year-old woman presented with a 10-day history of jaundice, vomiting, and right upper-quadrant abdominal pain. This coincided with initiation of gliclazide therapy for her type 2 diabetes. There was no foreign travel, blood transfusions, or intravenous drug use, and she never drank alcohol. She also suffered from hypertension and temporal arteritis. Her other medications included long-term use of an angiotensin-converting enzyme inhibitor, metformin, prednisolone, lansoprazole, and atorvastatin. She denied any use of other over-the-counter medications or analgesia. She had no stigmata of chronic liver disease. On presentation, she had acutely deranged liver function tests. Bilirubin was 166, alkaline phosphatase 741, alanine aminotransferase 648, and international normalized ratio 1.3. Full liver screen including viral and autoimmune antibody tests was negative. Ultrasound abdomen in conjunction with computed tomography and magnetic resonance cholangiopancreatography showed evidence of gallstones but ruled out obstructive causes of her jaundice. Her gliclazide was suspended, and liver function tests were monitored. She was started on rifampicin as a trial. Liver function tests gradually improved on cessation of therapy. Bilirubin returned to normal after 6 weeks. As her liver function tests were improved, the rifampicin was stopped, and further invasive investigations were deemed unnecessary.
were used with dose adjustment by weight. Sixty-five percent of patients (13/20) had also received other image studies such as CT or MRI. We follow the practical guideline from Dr. Claudon for diagnosis of FLL (Claudon et al., Ultraschall. Medn 2013;34: 11-29). Results: Sixteen of the 20 patients were male. Two patients did not receive CEUS study due to uncertainty of heart disease and suboptimal baseline US study. Fifty percent of the patients (10/20) were diagnosed as hepatocellular carcinoma (HCC) by CEUS, and six patients were confirmed by either CT or MRI with the diagnosis of HCC. Four patients were diagnosed as hemangioma with typical peripheral enhancement during arterial phase and centripetal fill-in during portal phase and late phase. All four hemangiomas were confirmed either by CT or MRI. Two patients were diagnosed as focal nodular hyperplasia that presented with typical finding with a hyperenhancing pattern from the center in the arterial phase then rapid fill out. Two patients had inconclusive CEUS finding. All patients tolerated the examination well without side effects. Conclusion: CEUS can be a potential tool for diagnosis of FLL, especially in patients with renal impairment who are not suitable for CT or MRI with contrast imaging study. In this preliminary study, only one patient diagnosed as HCC had been confirmed by pathologic result. Further study is needed to compare CEUS, CT, or MRI and pathologic findings.