The effect of pegylated interferon-α on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection

Background/Aims: To determine the response to pegylated interferon-α treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance. Methods: Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20- 53), with a 26- week follow-up. Results: Two of 16 (12.5% ) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P=0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment. Conclusions: In the largest cohort study to date, pegylated interferon-α therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-α in chronic hepatitis B.