Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection

J Hepatol. 2010 Dec 10. [Epub ahead of print]

Lange CM, Moradpour D, Doehring A, Lehr HA, Müllhaupt B, Bibert S, Bochud PY, Antonino AT, Pascual M, Farnik H, Shi Y, Bechstein WO, Moench C, Hansmann ML, Sarrazin C, Lötsch J, Zeuzem S, Hofmann WP.

Medizinische Klinik 1, Germany; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue Bugnon 46, CH-1010 Lausanne, Switzerland.

Abstract

BACKGROUND AND AIM: Recent studies described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection.

METHODS: Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of which were treated with pegylated interferon-α(PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C.

RESULTS: Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected towards the adverse genotypes rs12979860CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No associations were observed between ALT / HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively).

CONCLUSIONS: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.

Copyright © 2010. Published by Elsevier B.V.

PMID: 21147186 [PubMed - as supplied by publisher]

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