title: HLA-DP genes polymorphisms associate with hepatitis B surface antigen kinetics and seroclearance during nucleot(s)ide analogue therapy.
abstract: OBJECTIVE
  Genome-wide association studies (GWAS) recently indicated that polymorphisms in the human leucocyte antigen (HLA)-DP genes were associated with risk of persistent hepatitis B virus (HBV) infection and clearance of HBV, but the effect of HLA-DP gene polymorphisms on the effect of antiviral therapy was unknown. We here investigated whether such polymorphisms were associated with decreases in HBsAg levels and seroclearance in patients who received long-term lamivudine (LAM) treatment.
  
  
  METHODS
  Japanese patients (202) who were hepatitis B e antigen positive at baseline, received LAM as first-line treatment, and consented to HLA-DP genotyping (HLA-DPA1 rs3077 and HLA-DPB1 rs9277535) were categorized into two cohorts, viz., a cohort who achieved virological response without rescue therapy (cohort 1) and those who did so with rescue therapy (cohort 2).
  
  
  RESULTS
  Serum HBsAg levels declined significantly between year 3 and 9 from baseline among cohort 1 patients possessing ≥2 A-alleles at rs3077 and rs9277535. The percentages of such patients in cohort 1 patients with decreases in HBsAg ≥0.5 log IU/ml were higher than those with <2 A-alleles (71.8% [28/39] vs. 38.9% [23/59]; P = 0.004). However, there was no significant difference in cumulative HBsAg seroclearance rates between patients with ≥2 and those with <2 A-alleles in cohort 1. In cohort 2, HBsAg seroclearance rates were higher in patients with ≥2 A-alleles than in those with <2 A-alleles (P = 0.003).
  
  
  CONCLUSIONS
  We found an association between HLA-DP polymorphisms and decreases in HBsAg levels and seroclearance among HBeAg-positive patients treated with LAM.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Taito
authors.initials: T
authors.lastname: Fukushima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006682:HLA-DP Antigens; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine
keywords: HLA-DP; hepatitis B surface antigen; lamivudine; nucleot(s)ide analogue