title: Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B.
abstract: BACKGROUND
  Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients.
  
  
  OBJECTIVE
  To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients.
  
  
  METHODS
  We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA <2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped.
  
  
  RESULTS
  Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA <2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA <2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response.
  
  
  CONCLUSIONS
  In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: W P
authors.initials: WP
authors.lastname: Brouwer
authors.forename: M J
authors.initials: MJ
authors.lastname: Sonneveld
authors.forename: F
authors.initials: F
authors.lastname: Tabak
authors.forename: K
authors.initials: K
authors.lastname: Simon
authors.forename: Y
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: U S
authors.initials: US
authors.lastname: Akarca
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: P
authors.initials: P
authors.lastname: Ferenci
authors.forename: J E
authors.initials: JE
authors.lastname: Heathcote
authors.forename: R J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: A
authors.initials: A
authors.lastname: Boonstra
authors.forename: B E
authors.initials: BE
authors.lastname: Hansen
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D059867:HLA-DP alpha-Chains / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006239:Haplotypes; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011092:Polyethylene Glycols