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 antibo dy (HBeAb)-positive patients with HBV chronic infection were studied, Patients were treated with prednisone (30 mg day(-1) for 4 weeks, foll owed by 20 mg day(-1) for 2 weeks and by 10 mg day(-1) for 1 week), fo llowed by recombinant interferon-alpha (15 MU thrice per week) for 6 m onths, without a clearance period. The HBV precore region was amplifie d by polymerase chain reaction (PCR) and distribution of the precore m utants was determined by hybridization of PCR Moreover, the glucocorti coid-responsive (GRE) was sequenced to determine whether changes in th e sequence were produced at the end of prednisone treatment. During pr ednisone treatment, changes in alanine transaminase (ALT) were observe d in only two patients, in whom 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 se ven patients were infected by a mixture of wild-type and precore mutan ts, predominantly wild type, At the end of prednisone treatment, two p atients were infected by only wild-type HBV. The proportion of precore mutants decreased in three cases, while no changes were observed in t hree, At the end of interferon treatment, the precore mutant proportio n decreased in the three responders, while tending to increase or rema in 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 mut ants.