Does ischemia-free machine perfusion lead to early allograft dysfunction (EAD) free liver transplantation?
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ABSTRACT:
SUBMITTER: Wadei H
PROVIDER: S-EPMC11336541 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:Background Early allograft dysfunction (EAD) is a common postliver transplant complication that has been associated with graft failure and risk for poor prognosis. There are many risk factors for the incidence of EAD after liver transplantation (LT). This study investigated whether elevated postoperative myoglobin (Mb) increases the incidence of EAD in liver transplanted recipients. Methods A total of 150 adult recipients who measured Mb within 3 days after liver transplantation between June 2019 and June 2021 were evaluated. Then, all patients were divided into two groups: the EAD group and the non-EAD group. Univariate and multivariate logistic regression analyses were performed, and receiver operating characteristic curves (ROCs) were constructed. Results The incidence of EAD was 53 out of 150 patients (35.3%) in our study. Based on the multivariate logistic analysis, the risk of EAD increased with elevated postoperative Mb (OR = 1.001, 95% CI 1.000–1.001, P = 0.002). The Mb AUC was 0.657, and it was 0.695 when combined with PCT. When the subgroup analysis was conducted, the AUC of serum Mb prediction was better in patients whose preoperative model for end-stage liver disease score ≤ 15 or operative time ≥ 10 h (AUC = 0.751, 0.758, respectively, or 0.760, 0.800 when combined with PCT). Conclusion Elevated Mb significantly increased the risk of postoperative EAD, suggesting that postoperative Mb may be a novel predictor of EAD after liver transplantation. The study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100044257, URL: http://www.chictr.org.cn).
| S-EPMC9597078 | biostudies-literature
Project description:Early allograft dysfunction (EAD) after living donor liver transplantation (LDLT) has often been attributed to inadequate graft size, and termed small-for-size syndrome. Early allograft dysfunction definitions include a variable constellation of findings, including hyperbilirubinemia, coagulopathy, encephalopathy, and ascites formation. Among putative causes of EAD after LDLT are excessive portal pressure and/or flow. Our objective was to evaluate patterns of EAD after LDLT.In this study, 631 LDLT recipients were monitored for complications, EAD (defined by postoperative day 7 bilirubin >10 mg/dL or international normalized ratio >1.6), and graft failure. Approximately 200 had portal venous and arterial pressure and flow measurements before and after LDLT. Portal inflow modification (splenic artery ligation, hemiportocaval shunt, or splenectomy) was performed at the discretion of the operating surgeon. Associations between EAD and recipient, donor, and transplant factors were examined using multivariable logistic regression.Risk of EAD was associated with left lobe grafts, lower graft weight among left lobes, higher preoperative bilirubin, higher portal reperfusion pressure, higher donor age, and higher donor body mass index. The risk of graft loss within the first 90 days was 5.2 times higher for recipients with EAD versus those without EAD (P < 0.001).Early allograft dysfunction can be defined using postoperative day 7 laboratory values that are highly predictive of early graft failure within 90 days. Risk factors associated with EAD after LDLT include: graft type and size, preoperative bilirubin, portal reperfusion pressure, donor age, and donor body mass index.
| S-EPMC4943080 | biostudies-literature
Project description:Early allograft dysfunction (EAD) identifies allografts with marginal function soon after liver transplantation (LT) and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction) who received renal replacement therapy (RRT) for a median (range) of 9 (13-41) days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30%) patients, and 22 (32%) patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016). Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002) and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007) were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery (P > 0.2 for all). Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes (P < 0.001). Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT.
| S-EPMC5908457 | biostudies-literature
Project description:BackgroundIschemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT.MethodsPatients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed.ResultsOf 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD.ConclusionGenerally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.
| S-EPMC9429388 | biostudies-literature
Project description:Background/objectivesSoluble CD163 (sCD163), a macrophage activation marker, is upregulated in conditions of macrophage proliferation and activation. Elevated sCD163 levels have been associated with liver disease severity and progression. During liver transplantation, the implanted liver is exposed to ischaemia and reperfusion injury, resulting in an acute inflammatory response and macrophage activation. The relationship between sCD163 levels during liver transplantation and the development of early allograft dysfunction (EAD) has not been investigated.MethodsWe included 27 cirrhosis patients (age 55 [range 32-72] years, 23 men) on the waiting list for liver transplantation. Alcohol consumption and viral hepatitis were the most frequent causes for cirrhosis. Patients were characterised by standard biochemical analysis and based on clinical disease severity scores. Information about donor, graft and course of the liver transplantation was recorded. sCD163 levels were measured at the time of liver transplantation before surgery, 2 h after reperfusion, and then at 24 h after transplantation.ResultsWe observed above-normal sCD163 levels at baseline (5.9 mg/L [4.7-8.8]). Two hours after reperfusion, sCD163 levels increased significantly from baseline (8.4 mg/L [7.4-10.9]; P < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9-5.5]; P < 0.01). However, in patients with EAD (n = 16), sCD163 levels were increased compared with patients without EAD (4.1 [3.2-7.4] vs. 3.1 [2.8-3.8] mg/L; P = 0.03).ConclusionsWe observed elevated sCD163 levels in patients with EAD after liver transplantation, confirming macrophage activation to play a role in EAD. Thus, sCD163 may be used as an early marker for EAD after liver transplantation, but larger studies are warranted to validate these findings.
| S-EPMC6637071 | biostudies-literature
Project description:Concepts to ameliorate the continued mismatch between demand for liver allografts and supply include the acceptance of allografts that meet extended donor criteria (ECD). ECD grafts are generally associated with an increased rate of complications such as early allograft dysfunction (EAD). The costs of liver transplantation for the health care system with respect to specific risk factors remain unclear and are subject to change. We analyzed 317 liver transplant recipients from 2013 to 2018 for outcome after liver transplantation and hospital costs in a German transplant center. In our study period, 1-year survival after transplantation was 80.1% (95% confidence interval: 75.8%-84.6%) and median hospital stay was 33 days (interquartile rage: 24), with mean hospital costs of €115,924 (SD €113,347). There was a positive correlation between costs and laboratory Model for End-Stage Liver Disease score (rs = 0.48, P < 0.001), and the development of EAD increased hospital costs by €26,229. ECD grafts were not associated with a higher risk of EAD in our cohort. When adjusting for recipient-associated risk factors such as laboratory Model for End-Stage Liver Disease score, recipient age, and split liver transplantation with propensity score matching, only EAD and cold ischemia increased total costs. Conclusion: Our data show that EAD leads to significantly higher hospital costs for liver transplantation, which are primarily attributed to recipient health status. Strategies to reduce the incidence of EAD are needed to control costs in liver transplantation.
| S-EPMC7917275 | biostudies-literature
Project description:Liver transplantation has become the ultimate treatment for patients with end stage liver disease. However, early allograft dysfunction (EAD) has been associated with allograft loss or mortality after transplantation. We aim to utilize a metabolomic platform to identify novel biomarkers for more accurate correlation with EAD using blood samples collected from 51 recipients undergoing living donor liver transplantation (LDLT) by 1H-nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography coupled with mass spectrometry (LC-MS). Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were used to search for a relationship between the metabolomic profiles and the presence of EAD.Cholesteryl esters (CEs), triacylglycerols (TGs), phosphatidylcholines (PCs) and lysophosphatidylcholine (lysoPC) were identified in association with EAD and a combination of cholesterol oleate, PC (16:0/16:0), and lysoPC (16:0) gave an optimal area under the curve (AUC) of 0.9487 and 0.7884 in the prediction of EAD and in-hospital mortality, respectively after LDLT. Such biomarkers may add as a potential clinical panel for the prediction of graft function and mortality after LDLT.
| S-EPMC6352109 | biostudies-literature
Project description:IntroductionSensitive and specific assessment of the hepatic graft metabolism after liver transplantation (LTX) is essential for early detection of postoperative dysfunction implying the need for consecutive therapeutic interventions.ObjectivesHere, we assessed circulating liver metabolites of the cholesterol pathway, amino acids and acylcarnitines and evaluated their predictive value on early allograft dysfunction (EAD) and clinical outcome in the context of LTX.MethodsThe metabolites were quantified in the plasma of 40 liver graft recipients one day pre- and 10 days post-LTX by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Plant sterols as well as cholesterol and its precursors were determined in the free and esterified form; lanosterol in the free form only. Metabolites and esterification ratios were compared to the model for early allograft function scoring (MEAF) which is calculated at day 3 post-LTX from routine parameters defining EAD.ResultsThe hepatic esterification ratio of all sterols, but not amino acids and acylcarnitine concentrations, showed substantial metabolic disturbances post-LTX and correlated to the MEAF. In ROC analysis, the low esterification ratio of β-sitosterol and stigmasterol from day 1 and of the other sterols from day 3 were predictive for a high MEAF, i.e. EAD. Additionally, the ratio of esterified β-sitosterol and free lanosterol were predictive for all days and the esterification ratio of the other sterols at day 3 or 4 post-LTX for 3-month mortality.ConclusionLow ratios of circulating esterified sterols are associated with a high risk of EAD and impaired clinical outcome in the early postoperative phase following LTX.
| S-EPMC5078158 | biostudies-literature
Project description:BackgroundIntestinal transplantation (IT) has become an important procedure for the treatment of irreversible intestinal failure. However, IT is extremely vulnerable to ischemia-reperfusion injury (IRI). Due to the limitations of static cold storage (SCS), hypothermic machine perfusion (HMP) is rapidly gaining popularity. In this study, the intestinal HMP system is established and HMP is compared with SCS.MethodsAn intestinal HMP system was built. Ten miniature pigs were randomly divided into the HMP and SCS groups, and their intestines were perfused using the HMP device and SCS, respectively, followed by orthotopic auto-transplantation. Analysis was done on the grafts between the two groups.ResultsOperation success rates of the surgery were 100% in both groups. The 7-day survival rate was 100% in the HMP group, which was significantly higher than that of the SCS group (20%, P< 0.05). The pathological results showed that fewer injuries of grafts were in the HMP group. Endotoxin (ET), IL-1, IL-6, IFN-γ and TNF-α levels in the HMP group were significantly lower than in the SCS group (P<0.05), whereas IL-10 levels were significantly higher (P<0.05).The intestinal expression levels of ZO-1 and Occludin were higher in the HMP group compared to the SCS group, whereas Toll-like receptor 4 (TLR4), nuclear factor kappa B (NFκB), and caspase-3 were lower.ConclusionsIn this study, we established a stable intestinal HMP system and demonstrated that HMP could significantly alleviate intestinal IRI and improve the outcome after IT.
| S-EPMC10011072 | biostudies-literature
Project description:BackgroundIschemia-reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia-free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI.MethodsSerum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT.ResultsPeak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that "metabolism of RNA" was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post-IFLT as they were post-CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients.ConclusionsIFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization.
| S-EPMC9042797 | biostudies-literature