Chronic Hepatitis B: A Treatment Update Vincent Wong, MD 1,2 Henry Chan, MD 1,2 1 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong 2 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Semin Liver Dis 2013;33:122–129. Address for correspondence Henry L.Y. Chan, MD, Department of Medicine and Therapeutics, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong (e-mail: hlychan@cuhk.edu.hk). In the past two decades, we have witnessed revolutionary changes in the treatment of chronic hepatitis B. The introduc- tion of peginterferon allows a finite course of treatment with convenient dosing. While hepatologists busied themselves managing drug resistance when lamivudine was first used, we now have potent oral nucleos(t)ide analogs (NAs) with high genetic barrier to resistance. This review is not meant to provide a comprehensive summary of the literature on differ- ent antiviral therapies, which has been covered in the regional guideline articles. Our focuses are on the practical aspects and controversies in the treatment of chronic hepatitis B. The role of virological tests in guiding treatment is also discussed. Goal of Treatment Various antiviral therapies can lead to normalization of serum alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA suppression, hepatitis B e antigen (HBeAg) seroconversion, hepatitis B surface antigen (HBsAg) seroclearance, and histo- logical improvement. At the end of the day, however, these are all just surrogate markers. The most important goal of treatment is prevention of hepatic mortality and morbidity like hepatocellular carcinoma (HCC) and cirrhotic complica- tions. The strongest evidence on the role of antiviral therapy in preventing clinical complications came from the Cirrhosis Asian Lamivudine Multicentre (CALM) Study. 1 In this place- bo-controlled randomized trial, lamivudine treatment for around 3 years reduced the risk of a composite end point of progression in the Child-Pugh score of 2 points or more, cirrhotic complications, HCC, and liver-related deaths from 17.7% to 7.8%. Subsequent meta-analyses including the CALM Study and other observational studies showed that lamivu- dine treatment, compared with placebo or no treatment, is associated with lower risk of HCC. 2 Successful treatment with Keywords ► peginterferon ► entecavir ► tenofovir ► cirrhosis ► hepatocellular carcinoma Abstract In the past two decades, there have been major developments in the treatment of chronic hepatitis B. Peginterferon can be given conveniently with weekly dosing, and its effect on hepatitis B e antigen seroconversion is highly durable. However, it carries numerous side effects and the treatment is successful in only 30 to 40% of patients. On- treatment hepatitis B surface antigen level is an indirect marker of the level and transcriptional activity of covalently closed circular DNA in the liver and may identify nonresponders to peginterferon. New oral nucleos(t)ide analogs such as entecavir and tenofovir can effectively suppress hepatitis B virus with minimal risk of drug resistance. Many patients, however, develop virologic relapse after cessation of oral antiviral therapy despite prolonged viral suppression and would require long-term treatment. During oral antiviral drug treatment, hepatitis B virus DNA monitoring is essential to assess treatment effect and drug adherence and detect drug resistance. In treatment- naïve patients, none of the drug combinations have been shown to be superior to monotherapy. Studies combining peginterferon and potent oral agents (entecavir and tenofovir) are underway. Tenofovir is effective in patients with lamivudine resistance and previous exposure to multiple agents. Its long-term ef ficacy as monotherapy in this setting warrants more studies. Issue Theme Current Perspectives on Chronic Hepatitis B; Guest Editors, Stephen Locarnini, MD, PhD, FRC(Path), and Alexander Thompson, MD, PhD, FRACP Copyright © 2013 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. DOI http://dx.doi.org/ 10.1055/s-0033-1345715. ISSN 0272-8087. 122