The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points.

The definite indications for the treatment of chronic hepatitis B are serum hepatitis B virus (HBV) DNA levels greater than 10(5) copies/mL and alanine aminotransferase (ALT) levels more than 2 times the upper limit of normal. If cirrhosis is present, an HBV DNA level greater than 10(5) copies/mL is the sole criterion for treatment. Treatment end points include hepatitis B e antigen (HBeAg) seroconversion for HBeAg-positive patients, reduction of HBV DNA levels to less than 10(5) copies/mL, and normalization of ALT values. These guidelines may apply to patients who acquire the hepatitis B infection during adolescence or adulthood but are less suitable for most hepatitis B carriers, who are infected in early life. Cirrhosis complications, including hepatocellular carcinoma, often occur in this latter group despite HBeAg seroconversion, HBV DNA levels less than 10(4) copies/mL, or ALT levels between 0.5 and 2 times the upper limit of normal. Therefore, HBeAg seroconversion may not be an adequate end point for these patients; the ideal treatment end points are permanent suppression of HBV DNA to levels undetectable by polymerase chain reaction and reduction of ALT levels to less than 0.5 times the upper limit of normal.