Impact of IL28B genetic variation on HCV-induced liver fibrosis, inflammation, and steatosis: a meta-analysis

Masaya Sato; Mayuko Kondo; Ryosuke Tateishi; Naoto Fujiwara; Naoya Kato; Haruhiko Yoshida; Masataka Taguri; Kazuhiko Koike

doi:10.1371/journal.pone.0091822

Impact of IL28B genetic variation on HCV-induced liver fibrosis, inflammation, and steatosis: a meta-analysis

PLoS One. 2014 Mar 17;9(3):e91822. doi: 10.1371/journal.pone.0091822. eCollection 2014.

Authors

Masaya Sato¹, Mayuko Kondo¹, Ryosuke Tateishi¹, Naoto Fujiwara¹, Naoya Kato², Haruhiko Yoshida¹, Masataka Taguri³, Kazuhiko Koike¹

Affiliations

¹ Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
² Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
³ Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.

Abstract

Background & aims: IL28B polymorphisms were shown to be strongly associated with the response to interferon therapy in chronic hepatitis C (CHC) and spontaneous viral clearance. However, little is known about how these polymorphisms affect the natural course of the disease. Thus, we conducted the present meta-analysis to assess the impact of IL28B polymorphisms on disease progression.

Methods: A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Integrated odds ratios (OR) were calculated with a fixed-effects or random-effects model based on heterogeneity analyses.

Results: We identified 28 studies that included 10,024 patients. The pooled results indicated that the rs12979860 genotype CC was significantly associated (vs. genotype CT/TT; OR, 1.122; 95%CI, 1.003-1.254; P = 0.044), and that the rs8099917 genotype TT tended to be (vs. genotype TG/GG; OR, 1.126; 95%CI, 0.988-1.284; P = 0.076) associated, with an increased possibility of severe fibrosis. Both rs12979860 CC (vs. CT/TT; OR, 1.288; 95%CI, 1.050-1.581; P = 0.015) and rs8099917 TT (vs. TG/GG; OR, 1.324; 95%CI, 1.110-1.579; P = 0.002) were significantly associated with a higher possibility of severe inflammation activity. Rs8099917 TT was also significantly associated with a lower possibility of severe steatosis (vs. TG/GG; OR, 0.580; 95%CI, 0.351-0.959; P = 0.034), whereas rs12979860 CC was not associated with hepatic steatosis (vs. CT/TT; OR, 1.062; 95%CI, 0.415-2.717; P = 0.901).

Conclusions: IL28B polymorphisms appeared to modify the natural course of disease in patients with CHC. Disease progression seems to be promoted in patients with the rs12979860 CC and rs8099917 TT genotypes.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Fatty Liver / etiology*
Female
Genetic Predisposition to Disease
Genetic Variation*
Genotype
Hepacivirus*
Hepatitis C / complications*
Hepatitis C / genetics*
Humans
Interferons
Interleukins / genetics*
Liver Cirrhosis / etiology*
Male
Odds Ratio
Polymorphism, Single Nucleotide
Sex Factors

Substances

interferon-lambda, human
Interleukins
Interferons

Grants and funding

This study was supported by the Global COE Program, “Center of Education and Research for Advanced Genome-Based Medicine: For personalized medicine and the control of worldwide infectious diseases”; the Ministry of Education, Culture, Sports, Science and Technology, Japan; by grants from the Leading Project of the Ministry of Education, Culture, Sports, Science and Technology, Japan; and by Health and Labor Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labor and Welfare, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.