Dataset Information

Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation.

ABSTRACT: In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.

SUBMITTER: Resch T

PROVIDER: S-EPMC8329650 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation.

Resch Thomas T Hackl Hubert H Esser Hannah H Günther Julia J Schwelberger Hubert H Ritschl Paul Viktor PV Ebner Susanne S Maglione Manuel M Mellitzer Vanessa V Biebl Matthias M Öllinger Robert R Zoller Heinz H Schneeberger Stefan S Kotsch Katja K

Frontiers in immunology 20210720

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value ...[more]

PMID: 34354697

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Project description:BackgroundThe reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.MethodsRecipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.ResultsEarly reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9-99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).ConclusionsObserved graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.

Project description:In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301-451) µg/kg/h versus those who did not 105 (70-158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = - 0.755) and aspartate transaminase (AST; R = - 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346-453) µg/kg/h) from those who were discarded (155 (87-206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients. The online version contains supplementary material available at 10.1007/s13167-024-00371-7.

Dataset Information

Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation.

Publications

Expression of MICA in Zero Hour Biopsies Predicts Graft Survival After Liver Transplantation.

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