Source

1 Department of Immunogenetics and Histocompatibility, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. 2 Liver Transplant Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. 3 Department of Internal Medicine Service, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. 4 Department of Pathology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. 5 Department of Statistics, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. 6 Department of Medicine, Universidad Autónoma de Madrid, Spain.

Abstract

BACKGROUND:

Polymorphisms of the IL28B gene (encoding interferon-λ3) determine the spontaneous course of hepatitis C virus (HCV) infection and its response to antiviral therapy. We investigated the influence of the IL28B rs12979860 (C>T) polymorphism on the risk of severe HCV recurrence after liver transplantation.

METHODS:

Ninety patients who underwent transplantation because of HCV cirrhosis were retrospectively analyzed; forty-one (45.6%) of them with severe HCV recurrence. Forty-eight of their paired donors were available and were also analyzed. IL28B rs12979860 was genotyped by real-time polymerase chain reaction, and evaluated for association with severe HCV recurrence, along with other variables, by univariate and multivariate analyses.

RESULTS:

The risk allele rs12979860-T was more common in transplanted patients (66.7%) than reported in healthy whites, and it was significantly overrepresented among patients with severe HCV recurrence, in comparison with patients without it (82.9% vs. 53.1%, odds ratio [OR]=4.30, etiologic fraction=63.6%; P=0.0028). Furthermore, separate analysis of the recipients' genotypes indicated that the risk of severe HCV recurrence increased with the dose of the T allele (linear trend, P=0.0068). Multiple logistic regression analysis confirmed the contribution of the IL28B genotype to the risk of severe HCV recurrence (OR=4.27; P=0.014), independently of other associated factors. Allele IL28B T in the donor seemed to have an opposite effect than that in the recipient (OR=0.46), but the study was underpowered to demonstrate this unforeseen effect (P=0.1995).

CONCLUSIONS:

The recipient IL28B rs12979860 genotype has a major influence on the posttransplantation course of HCV infection, being a valuable biomarker for patient care in liver transplantation.