Analysis of hepatitis B virus precore variants in hepatitis B e antibody-positive patients treated with prednisone plus interferon.

To assess the effects of prednisone and interferon on the distribution of hepatitis B virus (HBV) precore mutants, nine hepatitis B e antibody (HBeAb)-positive patients with HBV chronic infection were studied. Patients were treated with prednisone (30 mg day-1 for 4 weeks, followed by 20 mg day-1 for 2 weeks and by 10 mg day-1 for 1 week), followed by recombinant interferon-alpha (15 MU thrice per week) for 6 months, without a clearance period. The HBV precore region was amplified by polymerase chain reaction (PCR) and distribution of the precore mutants was determined by hybridization of PCR products. Moreover, the glucocorticoid-responsive element (GRE) was sequenced to determine whether changes in the sequence were produced at the end of prednisone treatment. During prednisone treatment, changes in alanine transaminase (ALT) were observed in only two patients, in who ALT decreased to nearly normal values. In three patients ALT normalized at the end of interferon treatment. At baseline, wild-type HBV alone was detected in one patient, while seven patients were infected by a mixture of wild-type and precore mutants, predominantly wild type. At the end of prednisone treatment, two patients were infected by only wild-type HBV. The proportion of precore mutants decreased in three cases, while no changes were observed in three. At the end of interferon treatment, the precore mutant proportion decreased in the three responders, while tending to increase or remain unchanged in the rest. No significant changes in GRE sequence were found as a result of prednisone treatment. Our results would appear to confirm the role of the immune system in the selection of precore mutants.