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

Abstract

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). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 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 > or = 3 log10 was seen in 3 patients.

CONCLUSIONS:

In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

• Authors: Scott K Fung, Pietro Andreone, Steve H Han, K Rajender Reddy, Arie Regev, Emmet B Keeffe, Munira Hussain, Carmela Cursaro, Pamela Richtmyer, Jorge A Marrero, Anna S F Lok
• Journal: Journal of hepatology (J Hepatol) Vol. 43 Issue 6 Pg. 937-43 (Dec 2005) ISSN: 0168-8278 [Print] Netherlands
• PMID: 16168522 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Organophosphonates
• adefovir
• Adenine

Topics

• Adenine (adverse effects, analogs & derivatives, therapeutic use)
• Adult
• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Disease Progression
• Drug Resistance, Viral (genetics)
• Hepatitis B (drug therapy, virology)
• Hepatitis B virus (genetics)
• Humans
• Liver Failure (etiology, virology)
• Male
• Middle Aged
• Mutation
• Organophosphonates (adverse effects, therapeutic use)
• Viral Load