IFNL4 ss469415590 polymorphism contributes to treatment decisions in patients with chronic hepatitis C virus genotype 1b, but not 2a, infection.

Abstract

Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P=0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR]=3.247, 95% confidence interval [CI]=1.038-10.159, P=0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥4×10(5) IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P=0.034, OR [95% CI]=7.24 [1.02-318.45], negative predictive value=92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P>0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen.

• Authors: Ruihong Wu, Xiumei Chi, Xiaomei Wang, Haibo Sun, Juan Lv, Xiuzhu Gao, Ge Yu, Fei Kong, Hongqin Xu, Rui Hua, Jing Jiang, Bing Sun, Jin Zhong, Yu Pan, Junqi Niu
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 39 Pg. 132-140 (Apr 2016) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 26820907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• IFNL4 protein, human
• Interferon alpha-2
• Interferon-alpha
• Interleukins
• Recombinant Proteins
• Ribavirin

Topics

• Adult
• Antiviral Agents (pharmacology, therapeutic use)
• Asian People (genetics)
• China
• Female
• Hepacivirus (classification, genetics)
• Hepatitis C, Chronic (drug therapy, genetics, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (pharmacology, therapeutic use)
• Interleukins (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Recombinant Proteins (pharmacology, therapeutic use)
• Retrospective Studies
• Ribavirin (pharmacology, therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)