title: Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.
abstract: 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.
authors.affiliation: Division of Gastroenterology, University of Michigan, Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Fung
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.forename: Steve H
authors.initials: SH
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Rajender Reddy
authors.forename: Arie
authors.initials: A
authors.lastname: Regev
authors.forename: Emmet B
authors.initials: EB
authors.lastname: Keeffe
authors.forename: Munira
authors.initials: M
authors.lastname: Hussain
authors.forename: Carmela
authors.initials: C
authors.lastname: Cursaro
authors.forename: Pamela
authors.initials: P
authors.lastname: Richtmyer
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Marrero
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine