IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection

• Published in: Journal of hepatology 2014-08, Vol.61 (2), p.235-241
• Main Authors: Eslam, Mohammed, Leung, Reynold, Romero-Gomez, Manuel, Mangia, Alessandra, Irving, William L, Sheridan, David, Spengler, Ulrich, Mollison, Lindsay, Cheng, Wendy, Bugianesi, Elisabetta, McLeod, Duncan, Zaitoun, Abed M, Attino, Vito, Goeltz, Diane, Nattermann, Jacob, Douglas, Mark, Booth, David R, George, Jacob, Ahlenstiel, Golo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Chronic hepatitis C; Female; Gastroenterology and Hepatology; Genotype; Genotype 2; Genotype 3; Hepacivirus - genetics; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - virology; Humans; IFNL3 (IL28B); Interferons; Interleukins - genetics; Male; Middle Aged; Polymorphism, Single Nucleotide; Response to therapy; SVR
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2014.03.039

Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 ( IFNL3 , previously known as IL28B ) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [ p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [ p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19–3.81) p = 0.0001 and OR 1.85 (1.15–2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders ( p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes ( rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.