Relation of IL28B Gene Polymorphism with Biochemical and Histological Features in Hepatitis C Virus-Induced Liver Disease

Department of Pharmacology, University of Extremadura, Cáceres, Spain.
PLoS ONE (Impact Factor: 3.23). 05/2012; 7(5):e37998. DOI: 10.1371/journal.pone.0037998
Source: PubMed


Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma.
We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards.
In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients.
The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.

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Available from: José M Ladero, Oct 06, 2015
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    • "However, its role in hepatocarcinogenesis remains conflicting [20] [21] [22], and the association between the cGT level and the development of HCC in patients with successful viral eradication has not been assessed. On the other hands, as interleukin 28B (IL- 28B) genetic variants have been the most important host factor associated with HCV treatment [23] [24] [25], its influence in HCC development remains unclear [26] [27]. The current study aimed to elucidate the incidence of HCC by prospectively following an HCV cohort who achieved an SVR. "
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    ABSTRACT: Background& Aims Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI. 2.32-10.71, P<0.001), followed by age (HR 1.06, 95% CI. 1.02-1.11, P=0.005) and r-GT levels (HR 1.008, 95% CI. 1.004-1.013, P<0.001). The incidence of HCC did not differ between patients with high and low baseline r-GT levels among patients with cirrhosis (P=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high r-GT levels compared with those with low r-GT levels (P=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline r-GT levels (HR 6.44, 95% CI. 2.20-18.89, P=0.001) and age (HR 3.68, 95% CI. 1.33-10.17, P=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high r-GT levels and cirrhotic patients (P=0.34). Conclusions HCC remains a threat in non-cirrhotic patients with an SVR. Serum r-GT levels helped to identify potential patients at high risk.
    Journal of Hepatology 07/2014; 61(1). DOI:10.1016/j.jhep.2014.02.022 · 11.34 Impact Factor
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    • "We had previously described an association of IL28B rs12979860 with serum lipids and steatosis [2] [3], both of which was confirmed in subsequent studies [4] [5] [6]. While steatosis was concordantly found to be associated with the less favorable IL28B genotypes (CT and TT) in patients with hepatitis C, a relation to inflammation was not reported. "
    Journal of Hepatology 10/2012; 58(2). DOI:10.1016/j.jhep.2012.09.035 · 11.34 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV)/human immunodefficiency virus (HIV) coinfection is a major health problem, affecting mostly to individuals with exposure to blood products, as hemophiliacs or intravenous drug users, or those exposed to high-risk sexual practices. Genotyping of interleukin 28B (IL-28B) rs12979860 polymorphism is a useful tool for guiding therapeutic decisions in this disease. On the contrary, there is not enough information on the pathogenic role of this polymorphism in the natural history of the disease. The objective of this study is to describe the relationships between the CT/TT genotype of this polymorphism with viral loads and also with a number of biomarkers of liver function in coinfected patients naïve for treatment for HCV. Seventy-five HCV/HIV coinfected patients were retrospectively recruited in our Hospital from 2010 to 2011. Logistic regression analysis adjusting by [Age], [Sex], [HCV viral genotype], [HCV viral load], [HIV viral load], and [CD4 T cells levels] revealed the IL-28B rs12979860 (CT/TT) genotype as a protective factor against alanine aminotransferase (ALT) levels (>100 IU/L), aspartate aminotransferase (AST) levels (>75 IU/L), and AST-to-platelet ratio index (APRI) score for liver fibrosis (>1.5) [OR, (95% CI), p]: ALT [0.026 (0.001-0.576) 0.021]; AST [0.001 (0.000-0.297) 0.019]; APRI [0.031 (0.002-0.41) 0.008]. Stepwise regression analysis considering the same adjusting variables showed the same results. In consequence, the IL-28B rs12979860 (CT/TT) genotype, which is a marker of poor response to HCV treatment, could be mediating on the contrary a certain protective effect against the hepatic damage caused by this virus in patients coinfected by HIV.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 10/2012; DOI:10.1089/jir.2012.0051 · 2.00 Impact Factor
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