title: HLA-DRB1*010101 allele is closely associated with poor virological response to lamivudine therapy in patients with chronic hepatitis B.
abstract: OBJECTIVE
  We intended to evaluate the association between specific human leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients.
  
  
  METHODS
  Six-digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB patients initially treated with LAM for at least 12 months. Antiviral response was evaluated every 3-6 months during LAM therapy.
  
  
  RESULTS
  Median age of the subjects was 43 years (range, 16-72). Median duration of LAM therapy was 69 months (range, 13-140). Median baseline serum hepatitis B virus (HBV DNA) level was 7.0 log(10) copies/ml (range, 5.5-9.1). At 12 months of LAM therapy, serum HBV DNA was undetectable by solution hybridization method in 308 (88%) patients. Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent alleles (>10%). HLA-DRB1*010101 was identified in 5.4% (18/334). The frequency of the HLA-DRB1*010101 allele was significantly lower in patients with virological response at 12 months of LAM therapy than in patients without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not associated with virological response. HBeAg loss/seroconversion and alanine aminotransferase normalization were not associated with HLA-DRB1 alleles.
  
  
  CONCLUSIONS
  The HLA-DRB1*010101 allele is closely associated with poor virological response to initial LAM therapy in CHB patients.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jin
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.forename: Jong Gi
authors.initials: JG
authors.lastname: Choi
authors.forename: Won Hyung
authors.initials: WH
authors.lastname: Park
authors.forename: Danbi
authors.initials: D
authors.lastname: Lee
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Yoon Seon
authors.initials: YS
authors.lastname: Lee
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D059811:HLA-DRB1 Chains; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000410:Alanine Transaminase