Background. The purpose of this study was to analyze the impact of extended donor criteria (EDC) and of changes in the Model for End-Stage Liver Disease (MELD) score while waiting for liver-transplantation (Δ-MELD) on patient survival and initial graft function. Methods. We included 386 consecutive patients with end-stage liver disease who underwent orthotopic liver transplantation at the Medical University Vienna between 1997 and 2003. Primary outcome was patient survival and secondary outcome was initial graft function. EDC included: age >60 years, >4 days intensive medical care, cold ischemia time >10 hr, need for noradrenalin >0.2 μg/kg/min or doputamin >6 μg/kg/min, a donor peak serum sodium >155 mEq/L, a donor serum creatinine >1.2 mg/100 mL, and a body mass index >30. Results. Δ-MELD was significantly higher in the nonsurvivor population (P=0.01) and EDC showed a significant influence on initial graft function (P=0.01). Worsening in either Δ-MELD or the presence of at least two EDC was not associated with an increased risk of primary graft dysfunction and death. Worsening in Δ-MELD and the presence of at least two EDC was significantly associated with primary graft dysfunction (P=0.01) and death (P=0.008). Conclusion. The combination of a liver recipient with worsening Δ-MELD and a potential donor with at least two EDC should be avoided.
Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor‐specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor‐specific parameters were correlated with 1‐year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ‐glutamyl transferase (γ‐GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ‐GT, and cause of donor death for 12‐month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor‐specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
Hypothermic oxygenated machine perfusion (HOPE) preconditions liver grafts before transplantation. While beneficial effects on patient outcomes were demonstrated, biomarkers for viability assessment during HOPE are scarce and lack validation. This study aims to validate the predictive potential of perfusate flavin mononucleotide (FMN) during HOPE to enable the implementation of FMN-based assessment into clinical routine and to identify safe organ acceptance thresholds. FMN was measured in perfusate samples of 50 liver grafts at multiple time points. After transplantation, patients were followed up for development of early allograft dysfunction (EAD), transplantation, and 1-year survival. FMN concentrations were significantly higher for grafts that developed EAD at 5 and 60 minutes into HOPE (p = 0.008, p = 0.026). The strongest predictive potential of FMN for EAD was observed at 5 minutes of HOPE with an AUC of 0.744. Similarly, 5-minute FMN was predictive for 1-year mortality (p < 0.001), reaching a remarkable AUC of 0.890. Cutoffs for prediction of EAD (10.6 ng/mL) and early mortality (23.5 ng/mL) were determined and allowed risk stratification of grafts. Particularly, patients receiving low-risk grafts developed EAD in 9% of cases, while all patients survived the first postoperative year. In contrast, high-risk organs developed an incidence of EAD at 62%, accompanied by the necessity of retransplantation in 38% of cases. One-year mortality in the high-risk cohort was 62%. Evaluation of FMN as early as 5 minutes during HOPE allows for risk stratification of liver grafts. Low-risk grafts, according to FMN, display a negligible risk for patients. Yet, high-risk grafts are associated with increased risk for EAD, transplantation, and early mortality and should not be used for transplantation without further assessment.
T-cell depletion is an essential aspect of clinical immunosuppression. The aim of the present study was to compare the efficacy of two dosage regimens in this setting. We retrospectively compared 246 patients (group 1) who received a 10-day antithymocyte globulin (ATG) induction protocol with 226 patients (group 2) who received a 3-day protocol. The 6-month rejection rate was 22.3% in group 1 and 12.7% in group 2 (P = 0.03). The sub-analysis showed a higher rejection rate in patients with cholestatic disease (P = 0.01), who were more numerous in group 1. This resulted in an overall difference between the groups. Rates of de novo malignancies and recurrent hepatocellular carcinoma were identical. Viral infection rates were 16% and 18%, respectively (P > 0.5). The rates of bacterial and fungal infection were also similar (37% vs. 42%, P > 0.1). However, infection and ATG administration are independent risk factors for survival. A lower rate of fatal infection was observed in group 2 (P = 0.01), while the 10-day ATG regimen had a detrimental effect on patients who had infection (P < 0.0001). Our results strongly support the application of 3-day ATG induction therapy regimen after orthotopic liver transplantation, as it is associated with the same rejection rate as long-term ATG induction therapy, without the negative survival effect of the latter due to lethal infection.
18 October 2024 in International Journal of Surgery
Background: Corroborating evidence for the use of hypothermic oxygenated machine perfusion (HOPE) prior to orthotopic liver transplantation (OLT) suggests a beneficial effect in regard to biliary complications. Here, the authors aim to evaluate whether perfusion via portal vein alone (sHOPE) or via additional perfusion of the hepatic artery (dHOPE) have diverging impact on outcomes after OLT when compared to the use of static cold storage (SCS). Methods: Consecutive patients undergoing OLT at the Medical University of Vienna (2018–2023) were retrospectively analyzed. Donor organs were procured using SCS, or subjected to end-ischemic sHOPE or dHOPE. The severity of biliary complications was classified according to the degree of therapeutic intervention (endoscopic retrograde cholangiopancreatography or surgical revision). Results: Two hundred forty-seven patients were included (69 SCS, 76 sHOPE, and 102 dHOPE). Hospitalization was shorter for patients after HOPE (median in days: SCS=25 vs HOPE=20, P=0.019). Biliary complications were less frequent in patients after HOPE (SCS=37.7% vs HOPE=22.5%, P=0.015). A significantly lower incidence of surgical revisions for biliary complications was observed in the HOPE cohort (24.6% vs 11.8%, P=0.012). When evaluating outcome according to HOPE-modality, a significant reduction in biliary complications (P=0.006) and surgical revisions (P=0.002) was only observed in dHOPE patients in comparison to SCS. Further, only dHOPE was significantly associated with a reduced need for surgical revision for biliary complications upon univariable and multivariable logistic regression (odds ratio=0.336, P=0.011). Conclusion: HOPE leads to a reduction of biliary complications and associated surgical revisions. This effect seems to be primarily associated with use of dHOPE, while both methods appear as feasible options for preconditioning of donor grafts prior to OLT.