Recently, the dinucleotide variant ss469415590 (TT/Delta G) 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 x 10(5) IU/ml), Delta G 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. (C) 2016 The Authors. Published by Elsevier B.V.
[1]Jilin Univ, Hosp 1, Dept Hepatol, 71 Xin Min St, Changchun 130021, Jilin Province, Peoples R China.
[2]Jilin Univ, Hosp 1, Dept Clin Epidemiol, 71 Xin Min St, Changchun 130021, Jilin Province, Peoples R China.
[3]Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, 320 Yue Yang St, Shanghai 200031, Peoples R China.
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