title: Mutations in HBV DNA polymerase associated with nucleos(t)ide resistance are rare in treatment-naive patients.
abstract: OBJECTIVE
  Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay.
  
  
  METHODS
  In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay.
  
  
  RESULTS
  Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1).
  
  
  CONCLUSIONS
  In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California.
authors.forename: Philip
authors.initials: P
authors.lastname: Vutien
authors.affiliation: Pacific Health Foundation, San Jose, California; San Jose Gastroenterology, San Jose, California.
authors.forename: Huy N
authors.initials: HN
authors.lastname: Trinh
authors.affiliation: Pacific Health Foundation, San Jose, California; San Jose Gastroenterology, San Jose, California.
authors.forename: Ruel T
authors.initials: RT
authors.lastname: Garcia
authors.affiliation: San Jose Gastroenterology, San Jose, California.
authors.forename: Huy A
authors.initials: HA
authors.lastname: Nguyen
authors.affiliation: San Jose Gastroenterology, San Jose, California.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Levitt
authors.affiliation: San Jose Gastroenterology, San Jose, California.
authors.forename: Khanh
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: San Jose Gastroenterology, San Jose, California.
authors.forename: Eduardo
authors.initials: E
authors.lastname: da Silveira
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California.
authors.forename: Tami
authors.initials: T
authors.lastname: Daugherty
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California.
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Garcia
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Lutchman
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California. Electronic address: mindiehn@stanford.edu.
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002140:California / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D024882:Drug Resistance, Viral; D005260:Female; D060005:Genotyping Techniques; D006515:Hepatitis B virus / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D004259:DNA-Directed DNA Polymerase
keywords: Baseline; CHB; Reverse; Transcriptase