Nancy Leung

HBeAg seropositivity is a marker for active viral replication. In the natural history of chronic hepatitis B infection, HBeAg marks the first two of the four phases, namely the immune tolerant phase and the immune clearance phase, and is associated with highly replicative activity of the hepatitis B virus (HBV). Most HBV consensus reports and guidelines recommend antiviral therapy if the immune clearance phase is prolonged and if there is evidence of significant necroinflammation and fibrosis. Two main types of antiviral agents have been approved for treating patients in the immune clearance phase: interferon and nucleos(t)ide analogues (NUCs). The endpoints of therapy are viral suppression with HBeAg seroconversion, undetectable serum HBV DNA, normalization of serum alanine transaminase and improvement in the histological necroinflammatory and fibrosis scores. The ultimate goal of therapy is to obtain clinical benefit for the patient by reducing complications including hepatocellular carcinoma (HCC). The choice between interferon-based immune modulators or NUCs that target the HBV DNA polymerase must be carefully weighed on an individual basis. Therapy with NUCs is often preferred by doctors and patients because it is easy to administer, with predictable efficacy and minimal side-effects. In specific patient subgroups such as those with decompensated disease, poor predictors of response or lack of response to interferon-based therapy and/or significant comorbidities that cannot tolerate interferon-induced side effects, NUCs therapy is the obvious choice. Entecavir and tenofovir are the treatments of choice because their efficacy and safety profile are better than lamivudine, adefovir and telbivudine. More importantly, there is a minimal risk of drug resistance during long-term therapy with these agents.

Hepatitis B virus (HBV) infection is a serious clinical problem affecting approximately 2 billion people worldwide. An estimated 350 million live with chronic hepatitis B (CHB) infection and are at an increased risk for serious liver sequelae and death from acute or chronic consequences of CHB infection. Individuals with CHB have a 20–30% risk of early death from complications, including liver cirrhosis and hepatocellular carcinoma. In the Asia-Pacific region, half of the CHB burden results from vertical or mother-to-child transmission, with early childhood horizontal transmission accounting for the remaining half. Screening and vaccination are key factors in the successful prevention and control of HBV infection. Over the last 20 years, the implementation of screening programs and universal HBV vaccination for all individuals born in endemic areas have reduced the prevalence of HBV infection and HBV-related liver diseases among individuals younger than 30 years. Women of childbearing age are key stakeholders in preventing HBV infection and, as such, play a critical role in reducing the vertical and horizontal transmission of HBV. Further efforts are needed to implement screening and educational programs for women of childbearing age, particularly those with CHB, to prevent the transmission of HBV to newborns, spouses, other household members, and sexual partners. In addition, healthcare workers need to learn how to avoid iatrogenic transmission in the healthcare setting. This article reviews these issues and highlights areas in which their engagement with public health efforts serves to improve quality of life and society as a whole.

This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside‐naïve adults with chronic hepatitis B (CHB). Sixty‐nine nucleoside‐naïve CHB patients with baseline HBV DNA of 10⁸ copies/mL or more were randomized 1:1 to open‐label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (−6.23 log₁₀ copies/mL versus −4.42 log₁₀ copies/mL, respectively; mean difference −1.58 log₁₀ copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV−ADV difference estimate: −0.66 log₁₀ copies/mL; 95% CI [−0.30, −0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir‐treated than adefovir‐treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV‐treated versus 15 (47%) ADV‐treated patients had HBV DNA of 10⁵ copies/mL or more. Both antivirals were well tolerated. Conclusion: Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside‐naïve HBeAg‐positive patients with CHB. (HEPATOLOGY 2009;49:72‐79.)

Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.

Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.

Objective: Hepatitis C virus (HCV) infection can lead to serious liver disease. Its medico-socio-economic burden on society can be immense. This study investigates the epidemiology of HCV infection in Hong Kong. Methods: Data from the Department of Health, relevant publications from Medline search and data from two acute hospitals were reviewed. Results: The prevalence of anti-HCV among voluntary blood donors is stable, remaining at approximately 0.035–0.099% over the past 10 years, and is higher in the older age group. Among the high-risk groups, the anti-HCV prevalence is as follows: (1) hospital patients 0.8%, (2) intravenous drug users 46.0%, (3) patients infected with HIV 7.9%, (4) children with transfusion-dependent hematologic disease 16.3%, (5) patients on continuous ambulatory peritoneal dialysis 1.8%, patients on hemodialysis 16.4%, recipients of kidney transplants 6.2% and (6) patients with hepatocellular carcinoma 7.3%. Among blood donors, 58.8% were infected with HCV genotype 1b and 27.0% with genotype 6a. Genotype 6a is particularly common among intravenous drug users. Conclusion: Hong Kong has a low prevalence of HCV infection. Patients are mostly infected through transfusion with blood or products prior to the introduction of anti-HCV screening to the blood transfusion service. Illicit drug use constitutes another significant risk. Since 1997, there has been a great increase in population movement between China and Hong Kong which might affect the epidemiology of HCV infection.