HEPATITIS-B VIRUS PRECORE CORE VARIATION AND INTERFERON THERAPY

Precore/core genes from hepatitis B e antigen (HBeAg)-positive and ant ibody to HBeAg (anti-HBe) positive individuals with active hepatitis h ave been analyzed to search for correlations with response to interfer on before and after treatment. Pretreatment, no precore stop codon mut ants were detected, even at the 3% level, in HBeAg-positive responders or nonresponders. In anti-HBe-positive patients, precore mutants did not influence response. No significant core amino acid variability was observed in HBeAg-positive patients, irrespective of interferon respo nse. However, anti-HBe-positive cases had multiple core protein substi tutions, mostly in B- and T-helper cell epitopes, but responders had f ewer (P =.02 for responders versus nonresponders and reactivators). No ne of four responders, three of seven reactivators, and three of three nonresponders had mutations within the major T-helper epitope from aa 50 to aa69 (P = .03). Precore mutants appeared in eight of nine natura l seroconverters compared with 3 of 10 interferon-induced anti-HBe ser oconverters (P = .01). Those in whom precore wild-type remained after treatment often tested negative in the last available sample using pol ymerase chain reaction (PCR), whereas emergence of mutants led to ongo ing viremia in all cases. In anti-HBe-positive cases, precore sequence s remained stable during therapy, except for 2 cases in whom a pre cor e mutant appeared accompanied by reactivation. In the core protein, an ti-HBe-positive cases selected a mean of 3.5, 1.6, and 1.7 amino acid substitutions in responders, nonresponders, and reactivators respectiv ely (P = NS). In conclusion, core but not precore sequence before ther apy may predict response. Appearance of precore mutants during therapy usually predicts failure to clear virus but substitution in core does not influence outcome.