Approximately 15% of Indian patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant-related CLD in Asian Indians. Eighteen patients (mean age 38.2 ± 12 years, M: F: 17: 1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti-HBe positive, HBV-DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV-DNA (both by dot-blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV-DNA by dot-blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 ± 12 vs 55 ± 29 IU/L, P < 0.01) and the histological activity index (15 ± 1.4 vs 12 ± 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 ± 0.4 g/dL vs 3.8 ± 0.4 g/dL, P= 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV-DNA positive at the end of follow up. This study concluded that:
1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians.
2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate.
3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.