A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation

Aging (Albany NY). 2020 Dec 3;13(1):1264-1275. doi: 10.18632/aging.202302. Epub 2020 Dec 3.

Abstract

Post-transplant liver fibrosis (PTLF) is a common and severe complication in liver recipients. In this study, we assessed the impact of donor liver genetics on the development of PTLF. A total of 232 patients undergoing liver transplantation were included. Twenty-two single nucleotide polymorphisms (SNPs) associated with liver fibrosis were analyzed. Univariate analysis revealed seven donor SNPs to be associated with PTLF. In a multivariate analysis, independent risk factors of PTLF were genetic variation of donor GRP78 rs430397 (OR = 8.99, p = 0.003), GSTP1 rs1695 (OR = 0.13, p = 0.021), miRNA-196a rs12304647 (OR = 16.01, p =0.001), and TNF-α rs1800630 (OR = 79.78, p = 0.001); blood tacrolimus levels at maintenance > 7 ng/ml (OR =7.48, p <0.001); and post-transplant diabetes mellitus (OR = 7.50, p = 0.001). A predictive model that included donor SNPs showed better prognostic ability for PTLF than a model with only clinical parameters (AUROC: 0.863 vs 0.707, P < 0.001). Given that donor gene SNPs are associated with an increased risk of PTLF, this model integrated with donor gene polymorphisms may help clinicians predict PTLF.

Keywords: liver fibrosis; liver transplantation; novel integrated model; single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus / epidemiology
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Genetic Predisposition to Disease
  • Glutathione S-Transferase pi / genetics
  • Graft Rejection / prevention & control
  • Heat-Shock Proteins / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / surgery*
  • Liver Failure, Acute / surgery*
  • Liver Transplantation*
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Postoperative Complications / blood
  • Postoperative Complications / epidemiology
  • Postoperative Complications / genetics*
  • Risk Factors
  • Tacrolimus / blood
  • Tacrolimus / therapeutic use
  • Tissue Donors*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Immunosuppressive Agents
  • MIRN196 microRNA, human
  • MicroRNAs
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Tacrolimus