When to Start and Stop Hepatitis B Treatment: Can One Set of Criteria Apply to All Patients Regardless of Age at Infection?

Existing guidelines for the treatment of hepatitis B virus (HBV) infection recommend that only patients with active or advanced liver disease and high serum HBV DNA levels be treated and that, in patients who are initially seropositive for hepatitis B e antigen (HBeAg), treatment can be stopped 6 months after HBeAg seroconversion (1–3). In this issue, Lai and Yuen (4) raise concern that those recommendations are inappropriate for patients with perinatal HBV infection. They propose that patients with normal alanine aminotransferase (ALT) levels who acquire infection early in life should also be treated and that HBeAg-positive patients should continue treatment after HBeAg seroconversion. The 2007 update of the American Association of the Study of Liver Disease guidelines (5) address some of Lai and Yuen's concerns by recommending that treatment also be considered for patients with intermittent or mildly elevated ALT levels; those who remain HBeAg- positive with high serum HBV DNA levels after 40 years of age; and HBeAg-negative patients with HBV DNA levels of 10 000 to 100 000 copies/mL (2000 to 20 000 IU/mL), particularly if liver histologic examination shows significant inflammation or fibrosis (5). Here, we put other aspects of their proposal in the context of existing evidence.

People with ALT values within the normal range are traditionally considered to have healthy livers. However, recent evidence suggests that the upper limits of normal in most diagnostic laboratories are erroneously high, owing to inclusion of patients with asymptomatic liver disease (6). Two studies reported that persons with ALT levels that are 0.5 to 1 times greater than the upper limit of normal had higher mortality from liver disease or cirrhosis complications than did persons with ALT levels less than 0.5 times the upper limit of normal (7, 8). Small studies have also found that up to one …