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Background and Aims Non-alcoholic steatohepatitis (NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological non-alcoholic fatty liver disease (NAFLD) activity score. Methods This was a placebo-controlled parallel-group double-blind randomized controlled trial. Patients with histology-proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile. Results We enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was −0.8 ± 1.4 in the Phyllanthus group and −0.3 ± 1.3 in the placebo group (P = 0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (−0.2 ± 0.7; P = 0.039) and ballooning grades (−0.4 ± 0.5; P

SummaryBackground On-treatment monitoring of serum hepatitis B virus (HBV) DNA to guide treatment strategy for patients on entecavir has received little attention. Aim To investigate the predictive value of on-treatment HBV DNA levels for responses to entecavir. Methods This was a retrospective cohort study among nucleos(t)ide analogue-naive HBV-infected patients on entecavir with a minimum follow-up of 2 years. Maintained virological suppression was defined as undetectable HBV DNA (

In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection in the general population.We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy.One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2-33.3) in HBV patients and 2.1% (0-44.2) in controls (p0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval [CI] 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls (p=0.003). The fatty liver prevalence differed in HBV patients and controls aged 40-59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p=0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p=0.034), but the difference was mainly attributed to lower triglyceride levels. Among HBV patients, viral genotypes, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver.HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies.

Objective Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population. Methods Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. Results Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was Conclusion NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.

Aliment Pharmacol Ther 2010; 32: 1059–1068 Summary Background The long-term benefit of interferon-alfa (IFN-α) treatment in preventing various hepatic complications is not certain. Aim To study the effects of IFN-α on reducing the risk of developing overall hepatic events (hepatocellular carcinoma, cirrhotic complications and liver-related mortality) in chronic hepatitis B patients. Methods Randomized controlled trials, case–control studies and cohort studies were retrieved from electronic databases and conference abstracts. Relative risks (RRs) of different hepatic complications among patients treated by IFN-α vs. no treatment or placebo were studied. Results Eleven studies were identified totalling 975 patients treated by IFN-α vs. 1147 untreated controls for analysis. Patients were treated by IFN-α for 1–24 months with a post-treatment follow-up of 1–13 years. Treatment by IFN-α reduced the risk of overall hepatic events (RR 0.55, 95% confident interval or CI 0.43–0.70, P

Background & Aims Histologic analyses of liver fibrosis have been limited by small sample sizes and the predominance of samples from patients with active hepatitis. Methods We performed a prospective study of transient elastography in treatment-naive patients with chronic hepatitis B, to investigate the relationship between hepatitis B virus (HBV) genotype and liver fibrosis. A validated liver stiffness measurement algorithm was used to define insignificant fibrosis and advanced fibrosis. Results Of 1106 patients, 711 (64%) were older than age 40, 370 (34%) had positive test results for hepatitis B e antigen (HBeAg), and 386 (35%) had increased serum levels of alanine aminotransferase. Of the patients, 524 (49%) had genotype B and 582 (51%) had genotype C HBV infection. Patients with genotype C infection had insignificant fibrosis less often (42% vs 55%; P P = .015) than those infected with genotype B HBV. The difference in the severity of liver fibrosis between the 2 HBV genotypes was most marked among patients older than age 40 and those who tested negative for HBeAg. The mean age of patients infected by genotype C was greater than that of patients infected by genotype B HBV (41 vs 36 y). Among patients who were older than age 40 and tested negative for HBeAg, those with genotype C infection had higher levels of HBV DNA and alanine aminotransferase than those with genotype B HBV. Conclusions Genotype C HBV was associated with more severe liver fibrosis than genotype B HBV, probably because of delayed HBeAg seroconversion and prolonged active disease.

Summary Background A meta-analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting. Aim To investigate the relative risk of HCC among the four major HBV genotypes (A–D). Methods A meta-analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All abstracts with keywords ‘hepatitis B’, ‘hepatocellular carcinoma’ and ‘genotype’ were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome. Results Nine hundred and eighty-eight abstracts were found through literature search, among them 43 studies were eligible for this meta-analysis. A total of 14 545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV-infected patients [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52–2.76, P

Non-alcoholic steatohepatitis (NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological non-alcoholic fatty liver disease (NAFLD) activity score.This was a placebo-controlled parallel-group double-blind randomized controlled trial. Patients with histology-proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile.We enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was -0.8 ± 1.4 in the Phyllanthus group and -0.3 ± 1.3 in the placebo group (P = 0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (-0.2 ± 0.7; P = 0.039) and ballooning grades (-0.4 ± 0.5; P0.001), the change was small and of limited clinical significance. Furthermore, there was no significant difference in the changes in alanine aminotransferase, aspartate aminotransferase, fasting glucose and lipid profile between the two groups.Phyllanthus is not superior to placebo in improving NAFLD activity score in NASH patients.

Background & Aims Unreliable results of liver stiffness measurement are obtained in 16% of cases and are independently associated with body mass index (BMI) greater than 30kg/m 2 . A new FibroScan® probe (XL probe) was designed specifically for obese patients. The aim of this study was to evaluate the accuracy of liver stiffness measurement using M and XL probes of Fibroscan® for the diagnosis of fibrosis and cirrhosis in a large cohort of patients. Methods Consecutive patients undergoing liver biopsies for chronic liver disease were prospectively recruited. Liver stiffness measurement was performed within 1week before liver biopsy using both M and XL probes of FibroScan®. Results A total of 286 patients were evaluated. A reliable liver stiffness measurement using M probe was obtained in 79.7% of cases. In the other 21.3%, liver stiffness measurement using XL probe was obtained in 56.9% of patients. A strong correlation was found between M and XL values, regardless of BMI. In all groups, median liver stiffness measurement using the XL probe was significantly lower than liver stiffness measurement using the M probe. By multivariate analysis, unsuccessful liver stiffness examination with M probe was independently associated with age >50years and BMI >30kg/m 2 . By univariate analysis, only BMI >30kg/m 2 was associated with unsuccessful liver stiffness measurement with XL probe. No significant difference was observed between the M and XL probes for the diagnosis of liver fibrosis. Conclusions Liver stiffness measurement with either M or XL probe is possible in 91.2% of patients with comparable diagnostic accuracy. In clinical practice, the M probe could be used as first step for liver stiffness measurement. In case of no valid shot or unreliable measurement, the XL probe could be used. This result could be useful for the assessment of liver fibrosis in NAFLD and/or obese patients.

Background & Aims Severe acute exacerbation of chronic hepatitis B is a unique clinical presentation with significant morbidity and mortality. Lamivudine was used in most previous studies, but the drug was limited by the development of resistance. Our objective is to study the safety and efficacy of entecavir in patients with severe acute exacerbation. Methods Consecutive patients with severe acute exacerbation of chronic hepatitis B were recruited from 1998 to 2009. All patients had serum alanine aminotransferase and bilirubin increased beyond 10 and 3 times the upper limit of normal, respectively. The primary endpoint was overall mortality at week 48. Virological and biochemical responses were also studied. Results Thirty-six patients and 117 patients were treated with entecavir and lamivudine, respectively. By week 48, 7 (19%) patients in the entecavir group and 5 (4%) patients in the lamivudine group died (adjusted hazard ratio 5.1, 95% confidence interval 1.5–17.2, p =0.010). Similarly, the entecavir group had higher liver-related mortality (adjusted hazard ratio 4.0, 95% confidence interval 1.0–15.7, p =0.044). Despite a lower prevalence of cirrhosis, more patients in the entecavir group developed prolonged jaundice, hepatic encephalopathy, and ascites. Entecavir resulted in more rapid and complete viral suppression, with 71% of patients achieving undetectable hepatitis B virus (HBV) DNA at week 48, compared to 40% in the lamivudine group ( p =0.007). However, rapid HBV DNA reduction at week 4 was associated with prolonged jaundice. Conclusions Entecavir treatment is associated with increased short-term mortality in patients with severe acute exacerbation of chronic hepatitis B but achieves better virological response in the long run.

BackgroundThe long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown.MethodsConsecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine amino-transferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls.ResultsForty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0–7.1) years and 3.8 (range 3.5–8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA 10copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for ≥6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment ( P=0.02).ConclusionAmong patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine.