Abstract: The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients. Materials and Methods: Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.
Keywords: interleukin 28B (IL28B) polymorphism; hepatitis C virus (HCV); histology; liver biopsy; fibrosis; necroinflammation; steatosis; natural history
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D'Ambrosio, R.; Aghemo, A.; De Francesco, R.; Rumi, M.G.; Galmozzi, E.; De Nicola, S.; Cheroni, C.; Clark, P.J.; Ronchi, G.; Lampertico, P.; Colombo, M. The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent. Int. J. Mol. Sci. 2014, 15, 7213-7224.
D'Ambrosio R, Aghemo A, De Francesco R, Rumi MG, Galmozzi E, De Nicola S, Cheroni C, Clark PJ, Ronchi G, Lampertico P, Colombo M. The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent. International Journal of Molecular Sciences. 2014; 15(5):7213-7224.
D'Ambrosio, Roberta; Aghemo, Alessio; De Francesco, Raffaele; Rumi, Maria G.; Galmozzi, Enrico; De Nicola, Stella; Cheroni, Cristina; Clark, Paul J.; Ronchi, Guido; Lampertico, Pietro; Colombo, Massimo. 2014. "The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent." Int. J. Mol. Sci. 15, no. 5: 7213-7224.