Association of Genetic Variants With Rapid Fibrosis

Abstract

Background Recurrence of hepatitis C, the main indication for liver transplantation in the United States, leads to rapid fibrosis progression and worse outcomes compared to other indications. While clinical variables play a role, they are insufficient to explain all inter-patient variability in posttransplant fibrosis progression. Genetic factors associated with hepatitis C virus (HCV) outcomes have been identified, but limited studies have been conducted in the context of HCV-related liver transplantation. Therefore, the purpose of this study was to examine candidate genes related to the immune response and rate of fibrosis in subjects undergoing liver transplantation for HCV. Methods One hundred twelve recipients with detailed posttransplant fibrosis and clinical information were genotyped using 25 single nucleotide variants (SNVs), including five SNVs within the IL28B gene region. Associations between SNVs and rapid fibrosis progression were performed controlling for pertinent clinical variables and haplotype analyses for the IL28B gene were completed. Results Significant multivariable associations were found for rs8099917 (IL28B), rs1991401 (DDX5), rs4969168 (SOC3), and rs7976497 (MLEC). The minor allele was protective against rapid fibrosis progression for the IL28B SNV (G allele), MLEC SNV (T allele), and DDX5 SNV (G allele). For the SOC3 SNV, the minor allele (A) increased the risk for rapid fibrosis progression. Additionally, two recipient haplotype structures for IL28B were significantly associated with rapid fibrosis progression. Conclusions These findings indicate that recipient genetic factors play a role in posttransplant HCV-related fibrosis progression. Molecular studies of these pathways may elucidate the pathogenesis of posttransplant fibrosis progression and provide risk prediction markers.

Cirrhosis Risk Score of the Donor Organ Predicts Early Fibrosis Progression after Liver Transplantation

“…Few data regarding the effect of genetic predisposition for FP exist in post-transplant patients. Layden et al [14] identified significant multivariate associations of FP in post-transplant HCV-infected patients with recipient gene variants of the interleukin 28B (IL28B), DEAD box protein 5 (DDX5), patatinlike phospholipase domain containing 3 (PNPLA3), suppressor of cytokine signaling-3 (SOCS3) and malectin (MLEC) genes [14].…”