IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: Role in the course of chronic viral hepatitis and the development of HCC

Articles in Press

Carlo Fabris 1, Edmondo Falleti 2, Annarosa Cussigh 2, Davide Bitetto 1, Elisabetta Fontanini 2, Sara Bignulin 1, Sara Cmet 2, Ezio Fornasiere 1, Elisa Fumolo 1, Stefano Fangazio 3, Andrea Cerutti 3, Rosalba Minisini 3, Mario Pirisi 3, Pierluigi Toniutto 1

Received 23 January 2010; received in revised form 8 July 2010; accepted 17 July 2010. published online 26 November 2010.
Uncorrected Proof

Background & Aims
A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory.

Methods
A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n=199), hepatitis B (n=75), alcohol (n=110) and other causes (n=28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls.

Results
A significant difference (p=0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p<0.005).

Conclusions
IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.

Keywords: Interleukin 28B, Hepatitis C, Liver cirrhosis, Hepatocellular carcinoma, Genetic polymorphisms

Abbreviations: HBV, hepatitis B virus, HCV, hepatitis C virus, HCC, hepatocellular carcinoma, IFN, interferon, SVR, sustained viral response, IL, interleukin, OLT, liver transplantation

1 Medical Liver Transplantation Unit, Internal Medicine, DPMSC, University of Udine, Italy
2 Laboratory Medicine, University of Udine, Italy
3 Department of Clinical and Experimental Medicine, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

Corresponding author. Address: Internal Medicine, Medical Liver Transplantation Unit, University of Udine, Piazzale S.M. Della Misericordia 1, 33100 Udine, Italy. Tel.: +39 0432559802; fax: +39 043242097.

PII: S0168-8278(10)00807-X
doi:10.1016/j.jhep.2010.07.019
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

Source