Effect of initial virologic response to adefovir on the development of resistance to adefovir in lamivudine-resistant chronic hepatitis B

BACKGROUND/AIMS: Adefovir dipivoxil (ADV) resistance in patients with lamivudine-resistant chronic hepatitis B is not well understood. This study examined the initial virologic response (IVR) to ADV, the rate of ADV resistance and the factors associated with ADV resistance. METHODS: Eighty one lamivudine-resistant HBeAg-positive patients were enrolled in this study. IVR was defined as HBV DNA < 4 log10 copies/mL after 6 months of therapy. RESULTS: IVR was observed in 37/81(45.7%) patients and it was associated with higher pretreatment ALT (P=0.002), and low pretreatment HBV DNA level (P=0.015). The HBV DNA levels were significantly higher in the non-IVR patients than the IVR patients at 12, 18 and 24 months (4.73 vs 2.59, 4.53 vs 2.31, 4.39 vs 2.40 log10 copies/mL, respectively; P<0.01). During the follow-up period, 17(21.0%) patients showed phenotypic resistance to ADV and 9 (11.1%) patients had ADV-resistant mutations. The cumulative probabilities of the phenotypic resistance to ADV at 12 and 24 months were 8.7% and 32.5%, respectively. The cumulative probabilities of the genotypic resistance to ADV at 12 and 24 months were 0% and 14.6%, respectively. Resistance to ADV was associated with a higher pretreatment HBV DNA (P=0.019), and non-IVR (P<0.001). CONCLUSIONS: The cumulative probabilities of the phenotypic and genotypic resistance to ADV at 24 months were 32.5% and 14.6%. The high pretreatment HBV DNA and non-IVR (HBV DNA >/= 4 log10 copies/mL after 6 months of therapy) were associated with ADV resistance.