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.
Highlights
Liver fibrosis (LF) can result from hepatic virus B (HBV) infection, excess alcohol-based liver disease, non-alcoholic fatty liver disease, autoimmune liver diseases, and hereditary diseases [1]
Given that donor gene single nucleotide polymorphisms (SNP) are associated with an increased risk of Post-transplant liver fibrosis (PTLF), this model integrated with donor gene polymorphisms may help clinicians predict PTLF
Clinical characteristic comparisons between the LF and the non-LF groups are shown in Table 1.Significant differences between the two groups included: Recipient age (P = 0.004), body mass index (BMI, P = 0.003), recipient primary disease (HCC or not, P = 0.028), tacrolimus level at maintenance (P = 0.005), and posttransplant diabetes mellitus (PTDM, P = 0.01)
Summary
Liver fibrosis (LF) can result from hepatic virus B (HBV) infection, excess alcohol-based liver disease, non-alcoholic fatty liver disease, autoimmune liver diseases, and hereditary diseases [1]. LF can progress to liver cirrhosis, which carries a risk for developing hepatocellular carcinoma (HCC) and other end-stage liver diseases. HBV recurrence, diabetes, immunosuppressors, and alcohol intake after LT will cause LF again. Post-transplant liver fibrosis (PTLF) can lead to new liver cirrhosis, which causes further life-threatening complications such as carcinoma or liver failure. Clinical research has shown that active HBV will drive liver inflammation and aggressive fibrogenesis [3]. Immunosuppressors such as tacrolimus advance fibrosis in liver transplant recipients in clinical trials [4]. Alcohol intake will induce hepatocellular injury and activate hepatic stellate cells (HSCs), which leads to liver fibrogenesis [6]
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