EFFECTS OF INTERFERON TREATMENT ON HBV PRE-CORE MUTANTS IN CHRONIC HEPATITIS B CARRIERS IN SINGAPORE

Abstract

The significance of the different hepatitis B virus (HBV) pre-core variants and their relationship to interferon treatment in chronic hepatitis B carriers were investigated. Ten chronic hepatitis B carriers (8 male, 2 female; age range 28-53yrs; 6 chronic active hepatitis (CAH), 4 chronic persistent hepatitis (CPH)) were given beta-interferon subcutaneously for 24 weeks. Eight other patients (5 male, 3 female; age range 24-58yrs; 4 CAH, 4 CPH) acted as controls. Patients are Chinese except one. Nine of the 10 treated patients had positive response with lowering of HBV DNA, ALT and AST levels while on interferon. Four CAH patients (66. 7%) and I CPH patient (25%) showed persistent loss of HBV DNA by blot hybridisation during follow-up after treatment. The common pre-core mutants found were stop codon mutant at codon 28 (nucleotide substitution from 'G' to 'A' at 1896), missense mutant at codon 15 (C' to 'T' at 1856), missense mutant at codon 29 ('G' to A' at 1899) with C28 stop codon mutation, and missense mutant at codon 29 ('G' to 'A' at 1898) with C15 mutation. Most carriers were found to harbour mix pre-core isolates of HBV. These mutants appear to occur randomly. C28 mutants were frequently found in CAH patients (5 of 10). CAH patients responded better than CPH patients to interferon treatment while the treatment had no selective effects upon the HBV mutants.