Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.
OBJECTIVE
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.
Fung
Scott K
SK
Division of Gastroenterology, University of Michigan, Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA.
Andreone
Pietro
P
Han
Steve H
SH
Rajender Reddy
K
K
Regev
Arie
A
Keeffe
Emmet B
EB
Hussain
Munira
M
Cursaro
Carmela
C
Richtmyer
Pamela
P
Marrero
Jorge A
JA
Lok
Anna S F
AS
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000235:genetics*; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D017093:Liver Failure / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine