Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B
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 HLADPA1 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.
|Persistent URL||dx.doi.org/10.1111/apt.12910, hdl.handle.net/1765/91840|
|Journal||Alimentary Pharmacology and Therapeutics|
Brouwer, W.P, Sonneveld, M.J, Tabak, F, Simon, K, Cakaloglu, Y, Akarca, U.S, … Janssen, H.L.A. (2014). Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B. Alimentary Pharmacology and Therapeutics, 40(7), 811–818. doi:10.1111/apt.12910