Polymorphisms of interferon‐λ4 and IL28B – effects on treatment response to interferon/ribavirin in patients with chronic hepatitis C. Issue 1 (10th November 2013)

• Record Type: Journal Article
• Authors: Stättermayer, A. F.; Strassl, R.; Maieron, A.; Rutter, K.; Stauber, R.; Strasser, M.; Beinhardt, S.; Datz, C.; Scherzer, T.‐M.; Steindl‐Munda, P.; Gschwantler, M.; Trauner, M.; Hofer, H.; Ferenci, P.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 39:Issue 1(2014)
• Page Start: 104
• Page End: 111
• Publication Date: 2013-11-10
• 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.12547
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12547-abs-0001"> <title>Summary</title> <sec id="apt12547-sec-0001" sec-type="section"> <title>Background</title> <p>The <italic>IL28B</italic> genotype in rs12979860 predicts success of peginterferon/ribavirin (PEG/RBV) therapy in patients with chronic hepatitis C (CHC). Recently, a dinucleotide frame shift variant in ss469415590 (TT or ΔG) was described, which generates the novel interferon lambda 4 protein (<italic>IFNL4</italic>). <italic>IFNL4</italic> ss469415590 (ΔG) allele carriers have an impaired clearance of HCV infection and response to IFN‐α therapy. In this study, we compared the role of <italic>IFNL4</italic> polymorphism with the two commonly used <italic>IL28B </italic>SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC.</p> </sec> <sec id="apt12547-sec-0002" sec-type="section"> <title>Aim</title> <p>To compare the role of <italic>IFNL4</italic> polymorphism with the two commonly used <italic>IL28B </italic>SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC.</p> </sec> <sec id="apt12547-sec-0003" sec-type="section"> <title>Methods</title> <p>A total of 754 PEG/RBV patients treated (male/female = 484/270; Caucasians: 98.8%; mean age: 42.8 [CI 95%: 42.0–43.6] y; genotype (GT)1: <italic>n</italic> = 435, GT2: <italic>n</italic> = 23, GT3: <italic>n</italic> = 185, GT4: <italic>n</italic> = 114) were investigated. Liver fibrosis was assessed by liver biopsy in 456 patients. Single nucleotide polymorphisms (SNPs) in ss469415590, rs12979860 and rs8099917 were analysed by RT‐PCR system.</p> </sec> <sec id="apt12547-sec-0004" sec-type="section"> <title>Results</title> <p>Of the patients, 12.9% (<italic>n</italic> = 97) had the ss469415590 ΔG/ΔG genotype (IFNL4), 51.3% (<italic>n</italic> = 387) were heterozygous (TT/ΔG) and 35.8% (<italic>n</italic> = 270) had TT/TT. <italic>IFNL4</italic> polymorphism was independently associated with SVR in GT1 (OR: 2.539, CI 95%: 1.629–3.021, <italic>P</italic> < 0.001) and GT4 (OR: 12.573, CI 95%: 3.427–46.133, <italic>P</italic> < 0.001), but not in GT3 (OR: 1.514, CI 95%: 0.933–2.458, <italic>P</italic> = 0.093).</p> <p> <italic>IFNL4</italic> correlated strongly with rs12979860 (ρ = 0.988, <italic>P </italic>< 0.001), but only moderately with rs8099917 (ρ = 0.598, <italic>P</italic> < 0.001).</p> </sec> <sec id="apt12547-sec-0005" sec-type="section"> <title>Conclusions</title> <p>These findings underscore the role of <italic>IFNL4</italic> for treatment response in patients with CHC genotypes 1 and 4. However, due to its strong correlation with rs12979860 in <italic>IL28B</italic>, there is no benefit in additional testing for <italic>IFNL4</italic> for treatment prediction in Caucasian patients. By contrast, <italic>IFNL4</italic> improves prediction of response to interferon‐based therapies, if SNP rs8099917 is used.</p> </sec> </abstract>