Abstract
Background
In patients with advanced fibrosis, primary end points of long-term or possibly indefinite antiviral therapy are sustained inhibition of viral replication and avoidance of emergence of resistance. In lamivudine-treated patients, the strongest predictor of emergence of YMDD mutations is baseline hepatitis B virus (HBV) DNA viral load. We aimed to verify whether abatement of viraemia by a short course of pegylated interferon (PEG-IFN-α2a) treatment before lamivudine treatment could prevent the emergence of lamivudine-associated mutations during long-term therapy.
Methods
A total of 14 patients with hepatitis B e antigen (HBeAg)-negative infection (3 lamivudine- experienced and 11 lamivudine-naive), with moderate/high viraemia (>106 copies/ml) and with Ishak stage 4-6 at liver biopsy were sequentially treated with 180 mg PEG-IFN-α2a for a period long enough to reach HBV DNA levels ≤103 copies/ ml or have a decrease of 3 log10 copies/ml from baseline. Lamivudine was then added to PEG-IFN-α2a treatment for 1 month and finally continued as monotherapy for 2 years or until viral breakthrough.
Results
Baseline HBV DNA (mean ±
Conclusions
In lamivudine-naive patients, abatement of HBV DNA<103 copies/ml by pretreatment with PEG-IFN-α2a completely prevents the emergence of YMDD mutants after 24 months of lamivudine monotherapy. This sequential schedule can optimize the use of a well tolerated, effective and inexpensive drug, such as lamivudine, in highly viraemic HBV patients.