Research Paper Volume 13, Issue 1 pp 1264—1275
A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation
- 1 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 2 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 3 NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, China
Received: July 16, 2020 Accepted: September 21, 2020 Published: December 3, 2020
https://doi.org/10.18632/aging.202302How to Cite
Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
ALT: alanine aminotransferase; APRI: aspartate aminotransferase -to-platelet ratio index; AGT6: Angiotensinogen 6; AUROC: The area under the receiver operating characteristic curve; AZNI1: antizyme inhibitor 1; BMI: body mass index; DCD: donation after cardiac death; ESR1: estrogen receptor α; FIB-4: fibrosis-4 index; GRP78: glucose-regulated protein 78; GSTP1: Glutathione S-transferase p1; GWAS: Genome-Wide Association Studies; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HLA: human leukocyte antigen; hOGG: human oxoguanine glycosylase; HSC: hepatic stellate cell; IFN: interferon; IL: interleukin; IQR: interquartile range; LF: liver fibrosis; LT: liver transplantation; MAF: minor allele frequency; MMP: matrix metalloproteinase; PD1: programmed cell death-1; PTDM: post-transplant diabetes mellitus; PTLF: post-transplant liver fibrosis; SNP: single nucleotide polymorphisms; TRPM5: transient receptor potential cation channel subfamily member 5; TNF: tumor necrosis factor; VDR: vitamin D receptor; XRCC: X-ray repair cross-complementing gene.