IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients
- 290 Downloads
Several single nucleotide polymorphisms (SNPs) within the interleukin 28B (IL28B) locus are associated with sustained viral response in chronic hepatitis C (HCV) patients who were treated with pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, an association between γ-GTP level and IL28B genotype was identified. In this study, the relationship between IL28B genotype and liver steatosis was analyzed.
One hundred fifty-three patients who underwent liver biopsy before PEG-IFN plus RBV combination therapy were enrolled. The level of liver steatosis was measured using a BIOREVO BZ-9000 microscope, and the proportion of fatty change and clear cell change were calculated using Dynamic cell count BZ-H1C software. IL28B SNP genotype (rs8099917) was determined using the Invader Assay.
Vesicular change was significantly associated with body mass index (BMI), HCV RNA titer, serum aspartate aminotransferase, γ-GTP, IL28B genotype and liver fibrosis level (P < 0.05). Clear cell change was significantly associated with serum aspartate aminotransferase, γ-GTP and IL28B genotype by univariate logistic regression analysis (P < 0.05). Under multiple logistic regression, IL28B genotype (ORadj = 8.158; 95% CI 2.412–27.589), liver fibrosis (ORadj = 2.541; 95% CI 1.040–6.207) and BMI (ORadj = 1.147; 95% CI 1.011–1.301) were significant independent factors for vesicular change and IL28B genotype (ORadj = 3.000; 95% CI 1.282–7.019) for clear cell change.
In this study, a new quantitative method to objectively evaluate hepatic steatosis was described. IL28B genotypes were significantly associated with both vesicular and clear cell changes of livers in chronic hepatitis C patients.
KeywordsHCV Core substitution IL28B Fatty change SNP
Hepatitis C virus
IFN-sensitivity determining region
Single nucleotide polymorphism
Body mass index
Gamma glutamyl transpeptidase
Homeostasis model assessment of insulin resistance
The authors thank Rie Akiyama for technical assistance and Aya Furukawa for clerical assistance. This study was supported by Grants-in-Aid for Scientific Research and Development from the Ministry of Education, Sports, Culture and Technology, and in part by a Grant-in-Aid from the Ministry of Health, Labor and Welfare of Japan, and was carried out at the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University, and the Analysis Center of Life Science, Hiroshima University.
Conflict of interest
- 18.Akuta N, Suzuki F, Hirakawa M, et al. A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response. J Med Virol. 2009;81:452–8.PubMedCrossRefGoogle Scholar
- 20.Akuta N, Suzuki F, Kawamura Y, et al. Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol. 2007;46:403–10.PubMedCrossRefGoogle Scholar
- 25.Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010;138:1338–45, 1345.e1–7.Google Scholar
- 40.Valenti L, Alisi A, Nobili V. I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology. Hepatology. 2011.Google Scholar