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A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation.

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-? 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.

SUBMITTER: Wang C

PROVIDER: S-EPMC7835018 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation.

Wang Chao C Zhang Xueyou X Ling Qi Q Zheng Shusen S Xu Xiao X

Aging 20201203 1

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 ...[more]

PMID: 33291080

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Project description:Acute kidney injury (AKI) is a frequent complication after living donor liver transplantation (LDLT), and is associated with increased mortality. However, the association between intraoperative oliguria and the risk of AKI remains uncertain for LDLT. We sought to determine the association between intraoperative oliguria alone and oliguria coupled with hemodynamic derangement and the risk of AKI after LDLT. We evaluated the hemodynamic variables, including mean arterial pressure, cardiac index, and mixed venous oxygen saturation (SvO₂). We reviewed 583 adult patients without baseline renal dysfunction and who did not receive hydroxyethyl starch during surgery. AKI was defined using the Kidney Disease Improving Global Outcomes criteria according to the serum creatinine criteria. Multivariable logistic regression analysis was performed with and without oliguria and oliguria coupled with a decrease in SvO₂. The performance was compared with respect to the area under the receiver operating characteristic curve (AUC). Intraoperative oliguria <0.5 and <0.3 mL/kg/h were significantly associated with the risk of AKI; however, their performance in predicting AKI was poor. The AUC of single predictors increased significantly when oliguria was combined with decreased SvO₂ (AUC 0.72; 95% confidence interval (CI) 0.68⁻0.75 vs. AUC of oliguria alone 0.61; 95% CI 0.56⁻0.61; p < 0.0001; vs. AUC of SvO₂ alone 0.66; 95% CI 0.61⁻0.70; p < 0.0001). Addition of oliguria coupled with SvO₂ reduction also increased the AUC of multivariable prediction (AUC 0.87; 95% CI 0.84⁻0.90 vs. AUC with oliguria 0.73; 95% CI 0.69⁻0.77; p < 0.0001; vs. AUC with neither oliguria nor SvO₂ reduction 0.68; 95% CI 0.64⁻0.72; p < 0.0001). Intraoperative oliguria coupled with a decrease in SvO₂ may suggest the risk of AKI after LDLT more reliably than oliguria alone or decrease in SvO₂ alone. Intraoperative oliguria should be interpreted in conjunction with SvO₂ to predict AKI in patients with normal preoperative renal function and who did not receive hydroxyethyl starch during surgery.

Project description:Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676?±?251 g (mean?±?SD), and percentage reconstitution was 80%?±?13%. Among recipients, GRWR was 1.3%?±?0.4% (8?<?0.8%). Graft weight was 60%?±?13% of SLV. Three-month absolute growth was 549?±?267 g, and percentage reconstitution was 93%?±?18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P?=?0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR?=?4.50, P?=?0.001) but not by GRWR or graft fraction (P?>?0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

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A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation.

Publications

A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation.

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