Donor IFNL4 Genotype Is Associated with Early Post-Transplant Fibrosis in Recipients with Hepatitis C

Abstract

Background and AimsEarly post-transplant hepatic fibrosis is associated with poor outcomes and may be influenced by donor/recipient genetic factors. The rs368234815 IFNL4 polymorphism is related to the previously described IL28B polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of this study was to identify the impact of donor and/or recipient IFNL4 genotype on early fibrosis among patients transplanted for hepatitis C (HCV).MethodsClinical data were collected for 302 consecutive patients transplanted for HCV. 116 patients who had available liver biopsies and donor/recipient DNA were included. 28% of these patients with stage 2 fibrosis or greater were compared to patients without significant post-transplant fibrosis with respect to clinical features as well as donor/recipient IFNL4 genotype.ResultsThe IFNL4 TT/TT genotype was found in 26.0% of recipients and 38.6% of donors. Patients who developed early post-transplant fibrosis had a 3.45 adjusted odds of having donor IFNL4 TT/TT genotype (p = 0.012). Donor IFNL4 TT/TT genotype also predicted decreased overall survival compared to non-TT/TT genotypes (p = 0.016).ConclusionsDonor IFNL4 TT/TT genotype, a favorable predictor of spontaneous HCV clearance pre-transplant, is associated with increased early post-transplant fibrosis and decreased survival.

The role of genetics in hepatic fibrosis among hepatitis C virus patients

“…It would, therefore, be important to extend the study to an African American population where linkage disequilibrium between these polymorphisms is lower and significant differences between rs12979860 and rs368234815 genotypes as predictors of HCV clearance are known (3). This is consistent with a study by Aiken et al who reports that the rs368234815 genotype is more strongly associated with the development of early post-transplant fibrosis than the rs12979860 genotype in a cohort of HCV-infected organ recipients that includes 19% African Americans (7). However, given that African Americans with chronic HCV infection have a slow disease progression rate, that fibrosis progression is not linear over time and that the effect of the rs12979860 [CC] genotype on liver fibrosis progression is stronger at early fibrosis transitions (F0 to F1 and F1 to F2) (1) it is important to define as closely as possible the time point at which early fibrosis stages are reached.…”

“…(3) This is consistent with a study by Aiken et al, who report that the rs368234815 genotype is more strongly associated with the development of early posttransplant fibrosis than the rs12979860 genotype in a cohort of HCV-infected organ recipients that includes 19% African Americans. (7) However, given that African Americans with chronic HCV infection have a slow disease progression rate, that fibrosis progression is not linear over time, and that the effect of the rs12979860 (CC) genotype on liver fibrosis progression is stronger at early fibrosis transitions (F0 to F1 and F1 to F2), (1) it is important to define as closely as possible the time point at which early fibrosis stages are reached. Ideally, this is based on histological results from two biopsies.…”