Adefovir dipivoxil (ADV) is effective in the treatment of chronic hepatitis patients with wild type and lamivudine-resistant hepatitis B virus. The occurrence of viral resistance to long-term adefovir therapy is rare, the cumulative rates of resistance were 0%, 3%, 11%, 18%, and 28% at 1, 2, 3, 4, and 5 years of therapy, respectively. The emergence of adefovir resistant mutant in patients with lamivudine resistance is more common than in treatment-naive patients. Two major mutations of adefovir resistance are rtN236T and rtA181V/T. Other mutations in the HBV polymerase (rtP237H, rtN238T/D, rtV84M, rtS85A, rtV214A, rtQ215S) reduce sensitivity to adefovir, but the significance of these mutations is unclear. The adefovir mutations slightly decrease adefovir susceptibility in vitro, suggesting mild clinical course after the occurrence of adefovir resistance. However, some patients show viral rebound and hepatic decompensation. Lamivudine, entecavir, and tenofovir are used currently for salvage therapy in patients with adefovir resistance. To reduce adefovir resistance, combination therapy with adefovir and lamivudine in patients with lamivudine resistance may be a treatment option. (Korean J Hepatol 2006;12:484-492)
