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Background and Aim: While hepatitis B virus (HBV) prevalence is known to vary greatly between countries, systematically collected population-level prevalence data from some countries is limited. Antenatal HBV screening programs in countries with substantial migrant populations provide the opportunity to systematically examine HBV prevalence in order to inform local and regional HBV estimates., Methods: A comprehensive register of Australian mothers giving birth from January 2000 to December 2008 was linked to a register of HBV notifications. Age-standardized prevalence of chronic HBV were calculated overall and by the mother's country of birth. Multiple logistic regression was used to investigate other factors associated with HBV prevalence., Results: Five hundred twenty-three thousand six hundred sixty-five women were included and linked to 3861 HBV notifications. The age-standardized HBV prevalence was low (0.75%, 95% confidence interval 0.72-0.79). The highest HBV prevalence rates were observed in women born in Cambodia (8.60%), Taiwan (8.10%), Vietnam (7.49%), China (6.80%), and Tonga (6.51%). Among Australia-born women, those who smoked during pregnancy, were from a more disadvantaged socioeconomic background, and lived in remote areas were more likely to have HBV. There was also a trend suggesting a decrease in the prevalence of HBV over time., Conclusions: Antenatal screening for HBV can provide systematic population estimates of HBV prevalence in migrants and also identify other high prevalence groups. Longer follow-up will be required to confirm the small decrease in HBV prevalence observed in this study., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aim: To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population., Methods: Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included., Results: A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC., Conclusions: The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems., Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor-node-metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared., Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow-up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child-Pugh-stage, alpha-fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3-month survival while CLIP performed better in predicting the outcome of 6- and 12-month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance., Conclusion: We have validated CUPI in a population composed of predominant HBV-related HCC. CUPI is an appropriate staging system for HBV-related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aims: To assess the efficacy of switching Japanese chronic hepatitis B patients from lamivudine monotherapy to entecavir 0.5 mg/day., Methods: A retrospective analysis was conducted on 134 patients switched to entecavir between September 2006 and February 2008 for 6 months or more. Patients were divided into three groups based on viral load at entecavir switching point (baseline < 2.6, 2.6-5.0 and > 5.0 log(10) copies/mL)., Results: At baseline, detection of lamivudine-resistant virus was highest in patients with higher hepatitis B virus (HBV) DNA (76% vs 23% in > or = 2.6 and < 2.6 log(10) copies/mL, respectively), and in patients with longest previous exposure to lamivudine (52%, 28% and 24% for > 3 years, 1-3 years and < 1 year, respectively). Two years after entecavir switching, HBV DNA suppression to less than 2.6 log(10) copies/mL was achieved in 100% (32/32), 92% (12/13) and 44% (4/9) of patients in the less than 2.6, 2.6-5.0 and more than 5.0 log(10) copies/mL baseline groups, respectively. Alanine aminotransferase (ALT) normalization occurred in 76-96% and 90-100% of patients following 1 and 2 years of entecavir treatment, respectively. One patient (2.6-5.0 log(10) copies/mL) with lamivudine-resistant mutants at baseline developed entecavir resistance at week 48 during follow up., Conclusion: Switching to entecavir 0.5 mg/day achieves or maintains undetectable HBV DNA levels and ALT normalization over 2 years, especially in patients with viral load less than 5.0 log(10) copies/mL.

Background and Aims: The hepatitis B virus (HBV) reverse transcriptase (RT) plays an important role in viral replication. The aim of the present study was to characterize profiles of the RT region and to construct a database for further studies., Methods: Serum samples were obtained from 328 treatment naive patients chronically infected with HBV in five Chinese cities. Mutation status, genotypes and deep sequence analysis were carried out by amplifying and sequencing the RT region., Results: The base usage in the RT region differed at the mono- and dinucleotide level and thymidine dominated. The higher the variability of the strain was, the more it replicated. No significant clustering was found between our HBV RT sequences and those isolated 10 years ago (achieved from genebank). Nucleotide analogue resistance related mutants exist. The M204V/I mutation was found in 1.8% of the strains, 1.2% had L180M+ M204V/I, 0.6% had A181T/V, and only one had all three mutations. Minor strain mutants were found in 9.3% of the samples studied. The genotype B patients made up 36.6% (88.7% B2) and were mostly found in southern China, 63.4% (92.2% C2) were genotype C, and only one was genotype D. The average age of HBeAg positive genotype B patients was 29.5 +/- 10.4 years, for genotype C it was 36.1 +/- 10.9 (P < 0.001)., Conclusion: Primarily antiviral resistance related mutant strains do exist in treatment naïve patients. Without antiviral pressure, HBV strains evolved at a normal speed. In depth sequence analysis implied that viral replication might be correlated with its variability, which needs to be further investigated.

Background and Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV-related HCC survival., Methods: Data on HBV-related HCC cases was obtained from a community-based linkage study. HCC cases notified to the New South Wales (NSW) Central Cancer Registry (CCR) during the period 1994-2002 were linked to HBV notifications from the NSW Health Department. Age, sex, country of birth, year of diagnosis, tumor stage were extracted from the CCR database. Survival analysis was conducted to determine median survival and identify predictors of survival., Results: Over the 9-year study period, 278 HCC cases were linked to chronic HBV infection. The majority of cases were male (83.5%) and overseas-born (93.6%); Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was 15.0 months. HCC survival was poorer among older age groups (P < 0.0001), and among cases with regional spread (hazard ratio, 3.23; 95% confidence interval, 1.83-5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence interval, 2.44-6.08; P < 0.0001). Sex, region of birth and study period (1994-1997 vs 1998-2002) were not associated with HCC survival., Conclusion: The vast majority of HBV-related HCC were overseas-born, however, region of birth was unrelated to HCC survival. The continued extremely poor HCC survival, including lack of improvement in HCC survival in more recent years, suggests low uptake of HCC screening programs. Public health strategies including early diagnosis and appropriate referral for antiviral therapy assessment and increased HCC screening among high-risk populations are required to reduce HCC incidence and improve HCC survival.

Background and Aim: Entecavir has demonstrated clinical efficacy for chronic hepatitis B. This study evaluated the efficacy and safety of entecavir in nucleoside-naive Japanese chronic hepatitis B patients., Methods: In this multicenter, double-blind study, 66 nucleoside-naive Japanese chronic hepatitis B patients were randomized to 0.1 mg entecavir (n = 32) or 0.5 mg entecavir (n = 34) daily for 52 weeks. The primary endpoint was the proportion of patients whose serum hepatitis B virus (HBV) DNA decreased from baseline by > or =2 log(10) copies/mL or became undetectable (<400 copies/mL by polymerase chain reaction assay) at week 48., Results: One hundred percent of patients in both treatment groups achieved the primary efficacy endpoint, with 81% and 68% of patients achieving undetectable HBV DNA in the 0.1 mg and 0.5 mg treatment groups, respectively. Mean changes from baseline in HBV DNA were -4.49 log(10) and -4.84 log(10) copies/mL for the 0.1 mg and 0.5 mg groups, respectively. Significant improvements in necroinflammation were seen in both groups, as assessed by Knodell and New Inuyama classifications. Most adverse events were transient and classified as grade 1 or 2. There were no clinically significant differences in adverse events across the two treatment groups and no discontinuations due to adverse events in either group., Conclusions: In Japanese nucleoside-naive patients with chronic hepatitis B, 0.1 mg or 0.5 mg entecavir daily provided excellent efficacy and was well tolerated. The 0.5 mg dose was selected for the treatment of nucleoside-naive patients.

Background and Aims: The clinical significance of hepatic steatosis in chronic hepatitis B infection (CHB) is unclear. The aims of this study were thus to investigate the prevalence and risk factors for hepatic steatosis in patients with CHB and its relationship with liver injury., Methods: Consecutive patients with biopsy-proven CHB at Hangzhou Sixth People's Hospital between January 2005 and June 2007 were included. Patients co-infected with other viruses or suffering from liver disease of any other cause were excluded. Liver steatosis, necroinflammation and fibrosis were assessed by both Brunt and Scheuer classifications., Results: A total of 1915 patients (1497 men) with a mean age of 31 +/- 9.5 years were analyzed. Hepatic steatosis was present in 260 (14%) patients. The steatosis involved < 33% of hepatocytes in 90% of cases, and was more frequent among men than women (15% vs 8%, P < 0.001). Two-thirds (178 of 260) of patients with steatosis were hepatitis B e antigen (HBeAg)-positive, but there was no correlation with either serum HBeAg status or hepatitis B virus DNA titer. Degree of inflammation and fibrosis were more mild among those with steatosis than those without. Multivariate analysis showed that steatosis was independently associated with body mass index, serum triglyceride, apolipoprotein B, uric acid, and fasting blood glucose. However, fibrosis was only independently associated with age and inflammatory grade, and the latter associated with viral load and fibrosis stage., Conclusions: Hepatic steatosis is common in CHB, it is associated with metabolic factors not viral ones, and does not appear to affect the severity of liver disease.

The study of hepatitis B virus (HBV) immunity has been mainly focused on understanding the differences between subjects who are able to control HBV infection and patients with persistent infection. These studies have been instrumental in increasing our knowledge on the pathogenesis of the disease caused by HBV. However, it is possible that heterogeneity of host and virus factors which segregate in ethnically distinct HBV infected populations might modify important aspects of the immune response against HBV. In this review, we reexamine the kinetics and the pattern of HBV-specific immunity associated with control or persistence of infection. We then discuss how the epidemiological, genetic and viral characteristics peculiar to Asian patients can impact the profile of HBV-specific immunity.

Background and Aim: Australia has increasing immigration from hepatitis B virus (HBV) endemic countries of the Asia-Pacific region (APR). This study estimates immigration-related chronic HBV cases, chronic HBV prevalence, and HBV-related hepatocellular carcinoma (HCC) from 1960 to 2005 and projects HBV-related HCC to 2025 in Australia among people born in the APR., Methods: The populations of APR origin for the period 1960-2005 were derived from Australian census data. HBV prevalence from population-based sero surveys in the APR countries was used to estimate new chronic HBV cases (immigrant arrivals per year with chronic HBV). Age-specific incidence rates of HCC derived from a Taiwanese population-based study were used to estimate and project HBV-related HCC., Results: Chronic HBV cases among APR-born population increased rapidly from the late 1970s reaching a peak of 4182 in 1990. Chronic HBV prevalence increased to >53 000 in 2005. Estimates of HBV-related HCC increased linearly from one in 1960 to 140 in 2005, with a projected increase to 250 in 2025. Universal HBV vaccination programs in countries of origin had limited impact on projected HBV-related HCC to 2025., Conclusion: The burden of chronic HBV including HBV-related HCC among APR-born Australians has increased over the past three decades and is projected to increase further during the next two decades.

Background and Aims: Hepatitis B virus (HBV) core-related antigen (HBcrAg) and HBV core antigen (HBcAg) assays were developed for the measurement of serum HBV load. The aim of this study was to assess the clinical utility of these assays in Chinese patients with chronic genotype B and C HBV infection., Methods: One hundred and ninety-three chronic hepatitis B patients were enrolled. Serum HBcrAg and HBcAg were measured by chemiluminescence enzyme immunoassay, and HBV-DNA was measured by using a sensitive polymerase chain reaction assay. The data were analyzed in patients with HBV genotype B (HBV/B) and genotype C (HBV/C). The HBcrAg/HBcAg ratio was calculated and compared between patients with and without hepatitis B e antigen (HBeAg)., Results: The concentrations of HBcrAg and HBcAg showed significant positive correlation with the HBV-DNA concentration in both HBV/B (r = 0.79, P < 0.001, and r = 0.77, P < 0.001, respectively) and HBV/C (r = 0.87, P < 0.001, and r = 0.90, P < 0.001, respectively). The cut-off for a positive HBcAg corresponded to approximately 4.5 log copies/mL, and that for a positive HBcrAg result corresponded to 3-4 log copies/mL. The HBcrAg/HBcAg ratio was higher in patients with HBeAg than in those without HBeAg., Conclusions: The HBcrAg assay and HBcAg assay are clinically useful in viral quantitation of HBV/B and HBV/C. A combination of these assays would be a valuable tool for analyzing the clinical status of HBV infection.

Background: Nearly 14% of non-alcoholic chronic liver disease in India is related to hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. There are no clear data available from the literature on the therapeutic management of these patients who often suffer an unfavourable course., Methods: Fourteen consecutive cases of biopsy-proven chronic liver disease fulfilling the following criteria were included: Child's A or B liver disease, hepatitis B surface antigen positive, HBV-DNA positive, antibody to HCV positive and HCV-RNA positive. Seven patients had chronic liver disease (group I), while the remaining seven patients (group II) had additional disorders (non-Hodgkin's lymphoma (two), acute leukaemia (two), thalassaemia (two), chronic renal failure (one). Interferon alpha-2b (IFN) was given in a dose of 6 MIU thrice weekly for 6 months. Complete response was defined as loss of HBV-DNA and HCV-RNA at 6 months and sustained response (SR) as the sustained loss of HBV-DNA and HCV-RNA for more than 6 months during the follow-up period., Results: At the end of 6 months, alanine aminotransferase (ALT) levels remained unchanged (120 +/- 40 vs 136 +/- 64 IU/L), but six of the seven (86%) patients in group I lost HBV-DNA. All three hepatitis Be antigen (HBeAg)-positive patients lost HBeAg with an early flare of ALT (at 45 +/- 12 therapy days). Two of these patients (29%) lost HCV-RNA. Thus, SR was seen in 29%, while HBV-DNA loss was found in 100% during the follow-up period. In group II patients, there was a significant decrease in ALT (308 +/- 14 vs 65 +/- 25 IU/L, P < 0.001), but only three (43%) patients lost HBV-DNA and two (29%) lost HCV-RNA. One patient with acute leukaemia and another with renal failure had a complete response to IFN, but none of the lymphoma patients showed any antiviral response., Conclusions: In chronic hepatitis due to dual infection with HBV and HCV, interferon therapy is: (i) safe; (ii) effective (more so in clearing HBV); (iii) often associated with early ALT flare; and (iv) may be less effective if non-Hodgkin's lymphoma is present.

Approximately 15% of Indian patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant-related CLD in Asian Indians. Eighteen patients (mean age 38.2 +/- 12 years, M:F: 17:1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antige (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti-HBe positive, HBV-DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV-DNA (both by dot-blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV-DNA by dot-blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 +/- 12 vs 55 +/- 29 IU/L, P < 0.01) and the histological activity index (15 +/- 1.4 vs 12 +/- 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 +/- 0.4 g/dL vs 3.8 +/- 0.4 g/dL, P = 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV-DNA positive at the end of follow up. This study concluded that: 1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians. 2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate. 3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.