Polymorphisms of HLA‐DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B. Issue 7 (11th August 2014)

• Record Type: Journal Article
• Authors: Brouwer, W. P.; Sonneveld, M. J.; Tabak, F.; Simon, K.; Cakaloglu, Y.; Akarca, U. S.; Zeuzem, S.; Ferenci, P.; Heathcote, J. E.; de Knegt, R. J.; Boonstra, A.; Hansen, B. E.; Janssen, H. L. A.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 40:Issue 7(2014)
• Page Start: 811
• Page End: 818
• Publication Date: 2014-08-11
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12910
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12910-abs-0001"> <title>Summary</title> <sec id="apt12910-sec-0001" sec-type="section"> <title>Background</title> <p>Polymorphisms of the <italic>HLA</italic>‐<italic>DP</italic> gene are associated with the natural clearance of the hepatitis B virus in Asian patients.</p> </sec> <sec id="apt12910-sec-0002" sec-type="section"> <title>Aim</title> <p>To investigate the association of <italic>HLA‐DP</italic> polymorphisms with response to peginterferon (PEG‐IFN) in Caucasian chronic hepatitis B (CHB) patients.</p> </sec> <sec id="apt12910-sec-0003" sec-type="section"> <title>Methods</title> <p>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 <italic>HLA‐DPA1</italic> and <italic>HLA‐DPB1</italic> were genotyped.</p> </sec> <sec id="apt12910-sec-0004" sec-type="section"> <title>Results</title> <p>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. <italic>HLA‐DPB1</italic> was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1–3.0, <italic>P</italic> = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2–4.7, <italic>P</italic> = 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 <italic>HLA‐DPB1</italic> G‐allele (adjusted OR 2.7, 95% CI: 1.2–5.9, <italic>P</italic> = 0.012). Furthermore, <italic>HLA‐DPA1</italic> and <italic>HLA‐DPB1</italic> haplotype block GG showed comparable results for virological and combined response.</p> </sec> <sec id="apt12910-sec-0005" sec-type="section"> <title>Conclusion</title> <p>In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of <italic>HLA‐DP</italic> are independently associated with both virological and serological response to PEG‐IFN therapy at 6 months post‐treatment.</p> </sec> </abstract>