title: Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States.
abstract: OBJECTIVE
  Reported HBV drug resistance mutations among previously untreated patients with chronic hepatitis B are variable. Whether resistant HBV strains are transmitted in the acute setting is uncertain. We sought to document the presence of antiviral resistance (AVR) mutations in patients with acute HBV (AHB) infection.
  
  
  METHODS
  AHB infection was defined by HBsAg/IgM anti-HBc positivity, ALT>10X ULN and compatible clinical history. The TRUGENE HBV kit was used to perform genotyping and direct sequencing of the viral polymerase. INNO-LiPA HBV DRv2 and DRv3 were used to detect AVR mutations. Clonal sequencing was conducted on selected specimens.
  
  
  RESULTS
  Twenty-three patients were evaluated (mean age, 43 years; 54% male; 39% African American, 39% Caucasian, 13% Hispanic and 4% Asian). The mean peak ALT was 1554.2IU/L and mean peak total serum bilirubin was 12 mg/dl. The HBV DNA median viral load (N = 15) was 5.14 log(10)IU/ml. Nineteen patients were genotype A, and 1 each were genotype C, D, E and G. HBV drug resistance mutations were not detected by direct sequencing or INNO-LiPA. Clonal sequencing was conducted on 192 clones isolated from three patients and showed rtA181T, rtM250V and rtS202G mutations at an overall frequency of 1.54%, 1.39%, and 1.67% respectively.
  
  
  CONCLUSIONS
  We detected adefovir/lamivudine and entecavir relevant mutations in a minor population (<2%) of viral clones by clonal sequencing only. The clinical significance of these mutations is uncertain and may represent small populations of quasi-species vs. transmission of drug resistant strains.
authors.affiliation: Infectious Disease, Henry Ford Hospital, Detroit, MI, USA. Dbaxa1@hfhs.org
authors.forename: Dwayne M
authors.initials: DM
authors.lastname: Baxa
authors.forename: Ashish D
authors.initials: AD
authors.lastname: Thekdi
authors.forename: Alicia
authors.initials: A
authors.lastname: Golembieski
authors.forename: Prashant V
authors.initials: PV
authors.lastname: Krishnan
authors.forename: Omar
authors.initials: O
authors.lastname: Sharif
authors.forename: Anne
authors.initials: A
authors.lastname: Kizy
authors.forename: Lynne
authors.initials: L
authors.lastname: Shetron-Rama
authors.forename: John
authors.initials: J
authors.lastname: Jovanovich
authors.forename: Brandi J
authors.initials: BJ
authors.lastname: Chappell
authors.forename: Andrea
authors.initials: A
authors.lastname: Snow-Lampart
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
mesh_terms: D000208:Acute Disease; D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006509:Hepatitis B / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D009154:Mutation / Q000235:genetics*; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014481:United States / Q000453:epidemiology
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine