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.

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.

• Authors: W P Brouwer, M J Sonneveld, F Tabak, K Simon, Y Cakaloglu, U S Akarca, S Zeuzem, P Ferenci, J E Heathcote, R J de Knegt, A Boonstra, B E Hansen, H L A Janssen
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 40 Issue 7 Pg. 811-8 (Oct 2014) ISSN: 1365-2036 [Electronic] England
• PMID: 25109699 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• DNA, Viral
• HLA-DP alpha-Chains
• HLA-DP beta-Chains
• HLA-DPA1 antigen
• HLA-DPB1 antigen
• Hepatitis B e Antigens
• Interferon-alpha
• Polyethylene Glycols

Topics

• Adult
• DNA, Viral (analysis)
• Female
• Genotype
• HLA-DP alpha-Chains (genetics)
• HLA-DP beta-Chains (genetics)
• Haplotypes
• Hepatitis B e Antigens
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy, genetics, immunology)
• Humans
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Polymorphism, Genetic
• White People (genetics)
• Young Adult