Lamivudine, adefovir, and entecavir are safe and effective orally administered inhibitors of hepatitis B virus (HBV) replication, but drug-resistant strains of HBV with point mutations in the HBV polymerase gene are being reported with prolonged treatment that can lead to viral rebound and serum alanine aminotransferase flares. Salvage treatment with antiviral agents including investigational nucleoside/nucleotide analogues is available but highlights the limitations and hazards of sequential antiviral monotherapy for chronic HBV. Studies of pegylated interferon combined with an antiviral agent or dual nucleoside/nucleotide combination therapy are awaited to minimize the incidence of drug-resistant HBV and improve long-term outcomes.
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