Management of chronic hepatitis B

Abstract

Chronic hepatitis B affects 400 million people worldwide. The criteria for initiating and stopping treatment are still under debate in spite of well-established agents for its treatment. Hepatitis B virus (HBV) DNA level has been shown to be a major determinant for disease progression, and the development of complications of cirrhosis and hepatocellular carcinoma, which often occur after hepatitis B e antigen (HBeAg) seroconversion. The usually chosen level of alanine transaminase (ALT) for treatment initiation in various treatment guidelines is 2 times the upper limit of normal, but patients having ALT below this level are also at risk for the development of complications. Treatment should be started when HBV DNA levels are high (>2,000 IU/ml) and ALT levels are above upper limit of normal. Treatment should preferably be continued on a long-term basis for both HBeAg-positive and HBeAg-negative patients, until hepatitis B surface antigen seroconversion. The three first-line agents of treatment are interferon-α (IFN), entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Pegylated IFN is given for a limited period of 48 weeks, but a majority of patients continue to have detectable HBV DNA after treatment, and it has not been proven to decrease the incidence of hepatocellular carcinoma. ETV and TDF are both very potent antiviral agents able to maintain HBV DNA negativity when given on a long-term basis. The development of resistance for both drugs is low (1.2% after 6 years with ETV and 0% after 3 years with TDF). There is also histologic evidence with ETV that long-term treatment can decrease necroinflammation and reverse fibrosis/cirrhosis.