ContextSerum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B.ObjectiveTo evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma.Design, Setting, and ParticipantsProspective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992.Main Outcome MeasureIncidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems.ResultsThere were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41 779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100 000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100 000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P<.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk.ConclusionElevated serum HBV DNA level (≥10 000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.

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Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.

Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side-effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side-effects. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance. Promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).

Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

CHENNA H. ILOEJE,* HWAI–I YANG, JUN SU,* CHIN–LAN JEN, SAN–LIN YOU, HIEN–JEN CHEN,** and The Risk Evaluation of Viral Load Elevation and Associated Liver isease/Cancer-In HBV (the REVEAL-HBV) Study Group Global Epidemiology and Outcomes Research, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, (Wallingford, onnecticut); the Graduate Institute of Epidemiology, College of Public Health, National Taiwan University; and the **Genomics Research enter, Academia Sinica, Taipei, Taiwan

https://www.gastrojournal.org/article/S0016-5085(05)02276-6/pdf

CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Predicting Cirrhosis Risk Based on the Level of Circulating Hepatitis B Viral Load

Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was 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, indications for fibrosis assessment, 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 suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

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Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.27406

Cédric Blanpain

Papers

Hepatitis B virus infection [1] (multiple letters)

Reactivation of hepatitis B after transplantation in patients with pre-existing anti-HBs antibodies