Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
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 efficacy as monotherapy in this setting warrants more studies.