Berlakovich, Gabriela

Background and Aims: Hypothermic oxygenated machine perfusion (HOPE) improves outcomes in orthotopic liver transplantation (OLT), but reliance on University of Wisconsin machine perfusion solution (UW-MPS) increases costs and logistical burden. Histidine-tryptophan-ketoglutarate (HTK) has potential as a single-solution alternative for HOPE. This study evaluated the safety and efficacy of HTK versus UW-MPS during HOPE. Methods: A retrospective, propensity score-matched cohort study including 46 patients who received donation after brain death (DBD) grafts that were preserved with HOPE at the Medical University of Vienna between May 2018 and October 2024 was conducted. A total of 23 patients received grafts perfused with HTK; another 23 patients transplanted with organs perfused with UW-MPS were matched based on recipient age and sodium model of end-stage liver disease score, donor age and sex, cold ischemia time, and perfusion time. Postoperative outcomes, perfusion parameters, and cost differences were assessed. Results: The HTK and UW-MPS cohorts demonstrated comparable perfusion dynamics and vascular resistance. While arterial pressure and flow were higher in the UW-MPS group, clinical outcomes—including early allograft dysfunction (47.8% each), ICU stay, and comprehensive complication index—were statistically similar. A trend toward fewer biliary complications (13.0% vs. 30.4%) and reduced hemodialysis requirement (17.4% vs. 30.4%) was observed in the HTK group. Use of HTK reduced perfusion-related costs by approximately EUR 560 per procedure. Conclusion: HTK is a viable alternative to UW-MPS during HOPE in OLT of DBD grafts, offering comparable short-term outcomes and relevant cost savings. Prospective studies are warranted to validate these findings and explore broader applications of single-solution perfusion strategies.

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.

Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff’s criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.

Background. During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). Methods. A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. Results. It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. Conclusions. Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Background. The International Liver Transplantation Society (ILTS) has placed a strong focus on achieving gender equality and equity in liver transplant (LT). We aimed to understand gender distribution in leadership positions among LT physicians around the world and within ILTS. Methods. In 2019, the ILTS Equality, Diversity, and Inclusion Committee distributed a survey to obtain granular data on gender and characteristics of transplant physicians as well as those in leadership positions in each center. Additionally, data were collected on the gender composition of the ILTS membership, council, chairpersons, and committees and from the United Network for Organ Sharing. Results. Data were collected from 243 transplant centers. Thirty-two (13.2%) had at least 1 woman as the director of LT, chief of transplant surgery, or chief of transplant hepatology. Of the 243 centers, 133 reported the age and gender of the leadership personnel. Women physicians comprised 152 of the 833 transplant surgeons (18.2%) and 298 of the 935 hepatologists (31.9%). Among the 1331 ILTS physician members, 588 (44.2%) provided gender information in their member profiles, and 155 (26.3%) identified themselves as women. Of the 26 ILTS leadership positions, 7 (26.9%) were held by women. Conclusions. This analysis of worldwide gender distribution in the LT physician workforce showed notable gender disparity in LT leadership around the globe and within the ILTS. These data provide a launching point for promoting and achieving gender equality and equity in LT.

Background and Aims Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF‐Ag) and C‐reactive protein (CRP) are simple, broadly available markers of these processes. Approach and Results We determined whether addition of vWF‐Ag and CRP to the Model for End‐Stage Liver Disease‐Sodium (MELD‐Na) score improves risk stratification of patients awaiting LT. CRP and vWF‐Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting list mortality was assessed by receiver operating characteristics curve (ROC‐AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF‐Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF‐Ag and CRP both improved the predictive value of MELD‐Na for 3‐month waitlist mortality and showed the highest predictive value when combined (AUC: MELD‐Na, 0.764; MELD‐Na + CRP, 0.790; MELD‐Na + vWF, 0.803; MELD‐Na + CRP + vWF‐Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD‐Na, 0.677; MELD‐Na + CRP + vWF‐Ag, 0.882). vWF‐Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation. Conclusions The addition of vWF‐Ag and CRP—reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT—to the MELD‐Na score improves prediction of waitlist mortality. Using the vWFAg‐CRP‐MELD‐Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.