IFNL4-ΔG Genotype Is Associated With Slower Viral Clearance in Hepatitis C, Genotype-1 Patients Treated With Sofosbuvir and Ribavirin

被引：73

作者：

Meissner, Eric G. ^{[1
]}

Bon, Dimitra ^{[2
]}

Prokunina-Olsson, Ludmila ^{[3
]}

Tang, Wei ^{[3
]}

Masur, Henry ^{[4
]}

O'Brien, Thomas R. ^{[5
]}

Herrmann, Eva ^{[2
]}

Kottilil, Shyamasundaran ^{[1
]}

Osinusi, Anuoluwapo ^{[1
,6
,7
]}

机构：

[1] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[2] Goethe Univ Frankfurt, Inst Biostat & Math Modeling, Frankfurt, Germany

[3] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[4] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA

[5] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[6] Sci Applicat Int Corp Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA

[7] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2014年 / 209卷 / 11期

基金：

美国国家卫生研究院;

关键词：

viral kinetics; pharmacokinetics; IL28B; IFNL4; haplotype; SVR; hepatitis C virus; DAA therapy; relapse; INFECTION; HCV; VIRUS; KINETICS; THERAPY;

D O I：

10.1093/infdis/jit827

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Response to pegylated interferon-alpha and ribavirin (IFN-alpha/RBV) treatment for chronic hepatitis C virus (HCV) infection is influenced by host genetic factors, but their role for IFN-alpha-free, direct-acting antiviral (DAA) regimens is unclear. An exonic deletion allele (IFNL4-Delta G) bolsters the established association with IFN-alpha/RBV therapy treatment outcome of another IFNL4 variant, rs12979860, which is located upstream of IFNL3 (IL28B). We report that in patients treated with the DAA sofosbuvir along with RBV, IFNL4-Delta G is associated with slower early viral decay, due to slower loss of free virus (P = .039) and decreased drug efficacy (P = .048), suggesting functional relevance of IFN-lambda 4 in IFN-alpha-free DAA therapies.

引用

页码：1700 / 1704

页数：5

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