Increased risk of severe hepatitis C virus recurrence after liver transplantation in patients with a T allele of IL28B rs12979860.
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.
Department of Immunogenetics and Histocompatibility, Hospital Universitario Puerta de Hierro, Majadahonda, Spain.
Elisa
E
Cisneros
Isolina
I
Baños
María Jesús
MJ
Citores
Ana
A
Duca
Clara
C
Salas
Ana
A
Noblejas
María
M
Cañizares
Isabel
I
Millán
Valentín
V
Cuervas-Mons
Carlos
C
Vilches
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D017093:Liver Failure / Q000150:complications / Q000235:genetics / Q000628:therapy*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda