Review Hepatitis B Virus Resistance to Lamivudine and its Clinical Implications

Lamivudine is the first orally available drug approved for treatment of chronic hepatitis B, but hepatitis B virus (HBV) resistance to lamivudine appears to be a sine qua non in the therapy of HBV. The mutations at the FLLA and YMDD motif in the domains B and C of HBV polymerase contribute to this resistance. These mutations are found at codon (or AA) rtL180M and rtM204V/I in the reverse transcriptase (RT) domain of the HBV polymerase for all genotypes according to a new standardized RT domain numbering system. The resistant HBV may be less replication-competent in vitro and in vivo, and it is rarely associated with markedly increased HBV replication or liver injury. Therefore, certain physicians favour continuing lamivudine therapy even after emergence of HBV resistance with the expectation of maintaining lower-than baseline HBV DNA, alanine aminotransferase, and histological improvement, and avoiding reversion to wild-type HBV until additional antiviral strategies are developed. Ultimately, once several antiviral agents are approved, combination strategy is likely to be incorporated in antiviral treatment for chronic HBV to suppress, prevent or minimize the emergence of resistant virus.