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Background/Aims: The susceptibility of adefovir-resistant hepatitis B virus ( HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. Methods: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. Results: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47±13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). A t the time of adefovir resistance (mean of 20±9 months), HBV DNA increased to ≥5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepat ic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with l amivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by ≥3 log10 was seen in 3 patients. Conclusions: In conclusion, adefovir r esistance can be associated with significant viral rebound and hepatic decompens ation which may be fatal.
Background / Aims: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. Methods: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47 ± 13 years) were found to have adefovir-resistant mutations rtA181V / T or rtN236T. Baseline median ALT was 66 IU / L (range , 27-1161) and median HBV DNA 7.9 log10 copies / ml (range, 6-8.3). A t the time of adefovir resistance (mean of 20 ± 9 months), HBV DNA increased to ≥5 log10 copies / ml in 7 patients. After detection of adefovir resistance, hepat ic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with l amivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by ≥3 log10 was seen in 3 patients. Conclusions: In conclusion, adefovir r esistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.