Dataset Information

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

ABSTRACT: Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO?WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow-derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress-triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO?WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

SUBMITTER: Nakamura K

PROVIDER: S-EPMC7190917 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

Nakamura Kojiro K Kageyama Shoichi S Kaldas Fady M FM Hirao Hirofumi H Ito Takahiro T Kadono Kentaro K Dery Kenneth J KJ Kojima Hidenobu H Gjertson David W DW Sosa Rebecca A RA Kujawski Maciej M Busuttil Ronald W RW Reed Elaine F EF Kupiec-Weglinski Jerzy W JW

The Journal of clinical investigation 20200501 5

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic fl ...[more]

PMID: 32027621

Similar Datasets

Project description:Objective: The aim of this study was to explore the hemodynamic changes of hepatic artery and portal vein detected by Doppler ultrasound (DU) in infants who underwent living donor liver transplantation (LDLT). Methods: The data of 41 infant patients (22 Males, 19 Females, median age of 5 months) were collected in the Children's Hospital affiliated to the Chongqing Medical University from May 2018 to December 2019. The patients underwent left lateral segment LDLT (LLS -LDLT) because of biliary atresia (BA). Hemodynamic parameters, including the peak systolic velocity (PSV), resistivity index (RI) of the hepatic artery (HA), portal vein velocity (PVV), and portal vein flow (PVF) were recorded from Doppler ultrasound on the day before the operation, and on the 1st, the 7th, the 14th and the 30th day after LDLT procedures. The changes of PSVHA, RIHA, PVV and PVF before and on the 1st day after transplantation were analyzed by paired t-test. The comparison of the data between different postoperative time points were assessed by ANOVA. Results: Compared with the parameters measured before LDLT, PSVHA, and RIHA decreased, and PVV and PVF increased significantly (p < 0.001) on the 1st day after LLS-LDLT. As for PSV, there was no significant difference between the 7th day and the 1st day after transplantation (POD7 VS POD1, p = 0.167) while there was a substantial difference between the 14th, 30th and 1st day after LT (POD14 vs. POD1, p = 0.003) (POD30 vs. POD1, p < 0.001). And there was a significant difference between the 14th, 30th, and 7th days after LT (POD14 vs. POD7, p = 0.014) (POD30 vs. POD7, p < 0.001). There was no significant difference between 30th and 14th after transplantation (POD30 vs. POD14, p = 0.092). As for RIHA and PVV, the decrease was slow within the first month after the operation, and there was no significant difference at different times. Conclusion: We have identified major hepatic flow changes that occurred in 41 infants who underwent LLS -LDLT due to BA. The data could be used for future studies of LDLT in infants including hemodynamic modeling, liver regeneration and clinical management.

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.

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.

Dataset Information

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

Publications

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets