Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study

• Published in: PloS one 2015-12, Vol.10 (12), p.e0145105
• Main Authors: About, Frédégonde, Oudot-Mellakh, Tiphaine, Niay, Jonathan, Rabiéga, Pascaline, Pedergnana, Vincent, Duffy, Darragh, Sultanik, Philippe, Cagnot, Carole, Carrat, Fabrice, Marcellin, Patrick, Zoulim, Fabien, Larrey, Dominique, Hézode, Christophe, Fontaine, Hélène, Bronowicki, Jean-Pierre, Pol, Stanislas, Albert, Matthew L, Theodorou, Ioannis, Cobat, Aurélie, Abel, Laurent
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Anemia; Anemia - complications; beta 2-Glycoprotein I - genetics; Boceprevir; Care and treatment; Cirrhosis; Complications and side effects; Decision making; Dendritic cells; Dosage and administration; Drug dosages; Drug therapy; Drug Therapy, Combination; Gastroenterology; Genetic aspects; Genetic factors; Genetics; Hemoglobin; Hemoglobins - metabolism; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - virology; Human health and pathology; Humans; Immunology; Infections; Infectious diseases; Interferon; Interferons; Interleukins; Interleukins - genetics; Laboratories; Life Sciences; Liver; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - drug therapy; Liver Cirrhosis - genetics; Liver Cirrhosis - virology; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Patients; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Proline - adverse effects; Proline - analogs & derivatives; Proline - therapeutic use; Pyrophosphatases - genetics; Regression analysis; Ribavirin; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Telaprevir; Therapy; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145105

Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50-3.70], P = 2x10(-4)). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82-8.92], P = 8x10(-4)). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10(-5)). Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy.