R E V I E W Time for an active antiviral therapy for hepatitis B: An update on the management of hepatitis B virus infection Hee Bok Chae1,2,3 Hie-Won Hann1 1Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine; 2Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; 3Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea Correspondence: Hie-Won Hann Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine,Thomas Jefferson University, Philadelphia, PA 19107, USA Tel +1 215 955 5806 Fax +1 215 955 0770 Email hie-won.hann@jefferson.edu Abstract: Signiﬁcant advances in the management of chronic hepatitis B (CHB) have been made over the past decade. During this period we have witnessed improvements in survival as well as reduction of disease progression in CHB patients due to the introduction of effective antiviral therapy. The need for effective antiviral therapy is underscored by the results of the REVEAL-HBV study in which 3653 hepatitis B virus (HBV) carriers were followed over 12 year period. This study demonstrated that a persistently elevated serum HBV DNA level was the most important risk factor for the development of hepatocellular carcinoma (HCC). The ultimate goal of antiviral therapy for CHB patients should include halting the progression to cirrhosis and its life threatening complications and in preventing/reducing the development of HCC. An earlier study of 651 CHB patients with cirrhosis or advanced ﬁbrosis from countries in Asia also demonstrated that treatment with lamivudine (LVD) not only delayed disease pro- gression but also reduced the development of HCC. These landmark studies reafﬁrm the need for active antiviral therapy for CHB. Current treatment options for patients with CHB include interferon and nucleos(t)ide analogues. As we gain experience with these agents, it has become increasingly clear that long-term therapy beneﬁts patients with CHB. Keywords: pegylated interferon, lamivudine, adefovir, entecavir, tenofovir, telbivudine Case reports Since 1983, the author (HWH) has followed 6 families in which 16 children were identiﬁed as Hepatitis B surface antigen (HBsAg)-positive during high school or in college. Further investigation revealed all 16 children were born to HBsAg(+) moth- ers and were likely infected during childbirth. During subsequent years, HBsAg(+) members of 5 families were treated with antiviral agents, including LVD, adefovir (ADV), tenofovir (TDF) or entecavir (ETV) and they have remained well on therapy with normal liver function and liver imaging studies. Three children of the 6th family, however, did not receive therapy. Over the ensuing years, these children (now in their 40’s) remained asymptomatic although their liver enzymes were occasionally elevated. Ultimately, one of the three children, after only two weeks of fatigue, was found to have an advanced HCC with cirrhosis and splenomegaly. He, at the age of 44, passed away within 6 months of his HCC diagnosis. Immediately, the two remaining children elected to start antiviral therapy. In 2000, a 58 year-old Korean American man brought his older brother to Thomas Jefferson University Hospital for treatment of HCC. He himself had just completed interferon therapy for HBV and assumed he was cured. While his brother was undergo- ing cryosurgery he himself had an abdominal imaging and was found to have a 4 cm HCC in the right lobe of the liver. Laboratory studies revealed that he was Hepatitis B e antigen (HBeAg)-positive and had high levels of HBV DNA. He received radiofre- quency tumor ablation and was started on LVD. He developed LVD resistance 4 years Therapeutics and Clinical Risk Management 2007:3(4) 605–612 © 2007 Dove Medical Press Limited. All rights reserved 605