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Increased risk of adefovir resistance in patients with lamivudine‐resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy

Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment‐naïve chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV‐resistant mutations rtA181V/T and rtN236T between LAM‐resistant patients and treatment‐naïve patients at 48 weeks of ADV monotherapy. Fifty‐seven LAM‐resistant patients and 38 treatment‐naïve patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48‐week blood samples were analyzed for ADV‐resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real‐time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM‐resistant patients were found to have developed ADV‐resistant mutations, whereas none of the 38 treatment‐naïve patients developed such mutations (P < .01). Among LAM‐resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV‐resistant mutations than in those without such mutations (−1.04 vs. −2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM‐resistant patients than in treatment‐naïve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment. (HEPATOLOGY 2006;43:1385–1391.)