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

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J Hepatol. 2005 Sep 14; [Epub ahead of print]

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

hepatic decompensation.

Fung SK, Andreone P, Han SH, Rajender Reddy K, Regev A, Keeffe EB, Hussain

M, Cursaro C, Richtmyer P, Marrero JA, Lok AS.

Division of Gastroenterology, University of Michigan, Medical Center, 3912

Taubman Center, Ann Arbor, MI 48109-0362, USA.

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 66IU/L (range,

27-1161) and median HBV DNA 7.9log(10) copies/ml (range, 6-8.3). At the time

of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to

>/=5log(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 >/=3log(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.

PMID: 16168522