Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation

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 log(10) copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20 +/- 9 months), HBV DNA increased to >= 5 log(10) copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by >= 3 log(10) was seen in 3 patients. Conclusions: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.