Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B

Abstract Background: Anti-hepatitis e antigen-positive chronic hepatitis B is a progressive liver disease associated with precore mutant hepatitis B virus (HBV) and poor response to interferon. Therefore, precore mutant HBV may behave as an interferon-resistant virus. The relations between the prevalences of wild-type and precore mutant HBVs in baseline viremias and response to interferon were analyzed. Methods: Sera from 115 patients (59 treated and 56 untreated, followed up for 30 months) were tested using a quantitative oligonucleotide hybridization assay. Results: Spontaneous or interferon-induced recoveries were observed in 28.5% (6 of 21) and 47.3% (18 of 38) or in 0% (0 of 35) and 19% (4 of 21) of the patients with wild-type prevalent or mutant prevalent HBVs, respectively. Relapses occurred in 85.7% (12 of 14) and 19.4% (4 of 21) of treated patients with prevalent precore mutant and prevalent wild-type HBV, respectively ( P = 0.0001). High precore mutant HBV levels (>20% of total viremia) were associated with the lack of permanent response to interferon ( P = 0.01). Conclusions: Precore mutant HBV can influence the response to interferon when it reaches significant serum levels (>20% of total viremia). Therefore, chronic hepatitis B should be treated as early as possible in its natural history before precore mutant HBV is selected as a prevalent virus.