Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 ؋ upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2 ؋ ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2 ؋ ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 ؋ ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT >2 ؋ ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement, HBV DNA less than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2 ؋ ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negative CHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 ؋ ULN. (HEPATOLOGY 2010;51:1185-1189

This study aimed to quantify and evaluate the knowledge and awareness toward liver health and diseases as well as explore the attitudes and knowledge toward screening, diagnosis, and treatment of liver disease among the Thai population. This is a cross-sectional, self-reported and web-based questionnaire study. Awareness, perceptions and attitudes toward liver-related health and diseases as well as screening, diagnosis and treatment of liver diseases were assessed among 500 Thai adults. Respondents were mostly ≥35 years (62.0%) and females (52.0%). While there was an overall awareness regarding viral hepatitis as the main etiology of liver failure/cancer, respondents expressed misperceptions that hint at social stigmatization or discrimination toward infected individuals. A significant proportion lacked knowledge of liver screening tests and relevant diagnostic tests for viral hepatitis-related liver diseases. Screening or treatment costs and perception of being healthy were among reasons for not seeking medical consultation when exposed to risk factors or diagnosed. Treatment practices of hepatitis included prescription medication (59.1%), functional foods (51.8%) and traditional treatment (28.2%). Multivariate analysis identified income, recent health screening status and being diagnosed with liver disease(s) as significant predictors of the knowledge, attitude, and behaviors of the Thai population toward liver diseases. This study highlighted a degree of misperception and lack of in-depth understanding toward hepatitis-related liver diseases including poor attitudes and knowledge toward screening, diagnosis, and treatment of liver diseases. Factors identified suggest an unmet need to encourage proactive health-seeking behaviors to reduce transmission risks of hepatitis-related liver diseases within the community.

Conclusions Four HNF4-α specific shRNA expression plasmid were constructed, two of which has suppression effect on the HNF4α expression in hepatocytes. The effective two HNF4-α specific shRNA expression plasmids will be used for future studies on the function of HNF4-α in regulating HBV transcription and replication.Background Hepatitis B virus (HBV) infection is a worldwide health problem. Understanding of the HBV life cycle especially the replication mechanism may provide potential targets for the development of anti-HBV treatment. Objective To establish a small and convenient animal model with highly HBV replication, which can be used for functional studies of HBV replication mechanism. Methods HBV replication competent plasmid was transferred into 6-to-9-week-old BALB/C mice via tail vein within short time in a large volume that equivalent to 8% of the body mass of the mouse (hydrodynamic-based in vivo transfection procedure). After injection, these mice were sacrificed on day 1?3?4?5?7 and day 10, respectively, and the liver was collected. HBV DNA replication intermediate was analyzed by Southern Blot; The HBcAg in liver was checked by immunohistochemical technique; The serum HBsAg and HBeAg were detected by ELISA. Results After hydrodynamic-based transfer of the HBV replication competent construct via tail vein, high level of HBV DNA replication intermediates and HBcAg were detected in the mouse liver and HBsAg & HBeAg were detected in the serum, suggesting that HBV was replicated in the liver and secreted to the serum of the mouse. HBV DNA replication intermediates were detectable on day 1 and abundant on day 3, the levels were slightly decreased and stay at a relative stable level between days 4 and 7, and was almost undectable on day 10 after in vivo transfection. The expression patterns of HBVspecific antigens in the liver and serum were similar to that of HBV DNA. In addition, no obvious difference of HBV replication was observed in different parts of the mouse liver. Conclusion In this study, a rapid and convenient mouse model with high level HBV replication and expression was developed, which provided a very useful tool for the functional study of HBV. 4Hepatic steatosis is the sequel of oxidative stress elicited by HCV core protein: studies in vitro and in a conditionally transgenic mouse line 1 Activity changes of diamine oxidase and D(-)-lactate in blood and small intestine in liver fibrosis rats ZUO-JIONG GONG, SHI-LING SONG, PENG RUAN, QUAN-RONG ZHANG Wuhan University, ChinaObjective To investigate the significance of diamine oxidase (DAO) and D(-)-lactate activity changes in diagnosing intestinal mucosal impairment in liver fibrosis rats. Methods 14 wistar rats were divided into tow study groups: (1) healthy control group; (2) experimental group. Plasma levels of endotoxin, D(-)-lactate, DAO and small intestinal levels of D(-)-lactate and DAO were determinated by a spectrophotography. Results The concentrations of D(-)-lactate, DAO and endotoxin in experimental group were significant higher th...

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