The Association of IL28B Polymorphism and Graft Survival in Patients with Hepatitis C Undergoing Liver Transplantation

<div><p>Hepatitis C virus (HCV) infection is the leading cause of liver transplantation (LT) in Western countries. Polymorphism in the IL28B gene region has a major impact on the natural history and response to antiviral treatment in HCV. We investigated whether IL28B polymorphism was associated with graft survival in patients with or without HCV undergoing LT. 1,060 adult patients (age >18 years) underwent LT between years 2000 and 2008. Patients with previous LT, living donor LT and patients dying or requiring retransplants within 30 days of LT were excluded. DNA samples of 620 (84%) recipients and 377 (51%) donors were available for genotyping of IL28B rs12979860C>T. Donor IL28B genotypes had no significant differences in graft survival irrespective of HCV status. There was no difference in graft outcome in the non-HCV cohort (n = 293) based on recipient IL28B genotype. In the HCV group (n = 327), recipients with CC or CT genotype had better graft survival compared to TT genotype (62% vs. 48%, p = 0.02). HCV recipients with CC or CT genotype had delayed time to clinically relevant HCV recurrence compared to TT (10.4 vs. 6.7 months, p = 0.002). The beneficial effect of the CC/CT genotype on HCV recurrence and graft survival was independent of antiviral treatment. In conclusion, our study demonstrated that in contrast to donor IL28B genotype recipient IL28B was associated with graft survival and clinically relevant HCV recurrence in HCV infected recipients. No effect of IL28B genotype was manifest in non-HCV LT recipients.</p> </div

Recipient IL28B genotype and graft survival by HCV status.

<p>Kaplan-Meier curves for liver graft survival in HCV infected (A) and non-HCV recipients (B).</p

Donor and recipient characteristics based on recipient IL28B rs12979860 genotypes.

<p>LT = liver transplant; HCC = hepatocellular carcinoma; VL = viral load at the time of LT.</p

Donor IL28B genotype and graft survival by HCV status.

<p>Kaplan-Meier curves for liver graft survival in HCV infected (A) and non-HCV recipients (B).</p

Frequencies of donor and recipient IL28B rs12979860 genotypes in patients with or without HCV.

<p>Frequencies of donor and recipient IL28B rs12979860 genotypes in patients with or without HCV.</p

Relative expression of IL28 mRNA based on IL28B genotypes.

<p>There was no effect of IL28B genotypes on IL 28 mRNA expression. Median expression and range were shown.</p

Kaplan-Meier curves for survival free from HCV recurrence according to recipient IL28B genotypes.

<p>Only patients with a liver biopsy were included in the analysis. Percentage of patients without histological HCV recurrence on clinically indicated biopsies within first year after LT was higher in CC/CT compared to TT genotype (p = 0.002).</p

Flow diagram of study participants with available genotyping data.

<p>LT = liver transplantation.</p

Additional file 1: Table S1. of Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Tagging and coverage of MHC region markers. Table S2: Tagging and coverage of Tx-specific genes. Table S3: Untranslated regions (UTRs) considered in the TxArray design. Table S4: Loss-of-function variants included in the TxArray. Table S5: Copy number polymorphisms (CNPs) and variations (CNVs) included in the TxArray. (DOCX 54 kb