Diagnosis and treatment of chronic hepatitis B: 2009 update.

The diagnosis of chronic hepatitis B (CHB) is made using a combination of serological, virologic, biochemical, and histologic markers. The natural history of hepatitis B virus (HBV) infection can be divided into four phases: immune tolerance, immune clearance (HBeAg-positive chronic hepatitis B), inactive HBsAg carrier, and reactivation (HBeAg-negative chronic hepatitis B). Patients in the immune clearance and reactivation phases, with elevated alanine aminotransferase (ALT) and HBV DNA levels, are candidates for antiviral therapy. The primary determinant of treatment outcomes for CHB is suppression of serum HBV DNA, and long-term suppression of viral replication is likely to reduce progression to cirrhosis and hepatocellular carcinoma. Current antiviral treatment options for CHB include interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir. In patients with HBeAg-positive CHB, antiviral treatment is indicated when the serum HBV DNA level is 20 000 IU/mL and the ALT level is elevated. For HBeAg-negative patients, the threshold for initiation of therapy is lower, i.e., a serum HBV DNA level 2 000 IU/mL in association with an elevated ALT level. The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy may be useful in supporting the decision to initiate therapy, particularly in patients with normal ALT levels. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure adherence to therapy, confirm that the response to therapy is optimal, and survey for the development of resistance if an oral agent is used. Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, response to suboptimal suppression of viral replication, and the role of combination therapy.