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Polymorphisms of HLA ‐ DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B
Author(s) -
Brouwer W. P.,
Sonneveld M. J.,
Tabak F.,
Simon K.,
Cakaloglu Y.,
Akarca U. S.,
Zeuzem S.,
Ferenci P.,
Heathcote J. E.,
Knegt R. J.,
Boonstra A.,
Hansen B. E.,
Janssen H. L. A.
Publication year - 2014
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12910
Subject(s) - medicine , hbeag , odds ratio , immunology , genotype , gastroenterology , hepatitis b virus , hepatitis b , seroconversion , virology , hbsag , virus , biology , gene , biochemistry
Summary Background Polymorphisms of the HLA ‐ DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. Aim 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. Conclusion 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.