From large-for-size to large-for-flow: A paradigm shift in liver transplantation.

Liver graft-recipient matching remains challenging, and both morphologic and hemodynamic characteristics have been shown to be relevant indicators of post-transplant outcomes. However, no combined analysis is available to date. To study the impact of both morphologic and hemodynamic characteristics of liver grafts on transplantation outcomes, we retrospectively evaluated all consecutive 257 liver transplantations with prospective hemodynamic measurements from 2017 to 2020 in a single-center perspective. First, a morphologic analysis compared recipients with or without large-for-size (LFS), defined by a graft/recipient weight ratio >2.5% and excluding extreme LFS. Second, a hemodynamic analysis compared recipients with or without low portal flow (LPF; <80 mL/min per 100 g of liver tissue). Third, an outcome analysis combining LPF and LFS was performed, focusing on liver graft-related morbidity (LGRM), graft and patient survival. LGRM was a composite endpoint, including primary nonfunction, high-risk L-Graft7 category, and portal vein thrombosis. Morphologic analysis showed that LFS (n=33; 12.9%) was not associated with an increased LGRM (12.1% vs 9.4%; p =0.61) or impaired graft and patient survival. However, the hemodynamic analysis showed that LPF (n=43; 16.8%) was associated with a higher LGRM (20.9% vs 7.5%, p = 0.007) and a significantly impaired 90-day graft and patient survival. Multivariable analysis identified LPF but not LFS as an independent risk factor for LGRM (OR: 2.8%; CI:1.088-7.413; and p = 0.03), 90-day (HR: 4%; CI: 1.411-11.551; and p = 0 .01), and 1-year patient survival. LPF is a significant predictor of post-liver transplantation morbi-mortality, independent of LFS when defined as a morphologic metric alone. Consequently, we propose the novel concept of large-for-flow, which may guide graft selection and improve perioperative management of LPF.

A Single Preservation Solution for Static Cold Storage and Hypothermic Oxygenated Perfusion of Marginal Liver Grafts: A Preclinical Study.

BACKGROUND: Hypothermic oxygenated perfusion (HOPE) improves outcomes of marginal liver grafts. However, to date, no preservation solution exists for both static cold storage (SCS) and HOPE. METHODS: After 30 min of asystolic warm ischemia, porcine livers underwent 6 h of SCS followed by 2 h of HOPE. Liver grafts were either preserved with a single preservation solution (IGL2) designed for SCS and HOPE (IGL2-Machine Perfusion Solution [MPS] group, n = 6) or with the gold-standard University of Wisconsin designed for for SCS and Belzer MPS designed for HOPE (MPS group, n = 5). All liver grafts underwent warm reperfusion with whole autologous blood for 2 h, and surrogate markers of hepatic ischemia-reperfusion injury (IRI) were assessed in the hepatocyte, cholangiocyte, vascular, and immunological compartments. RESULTS: After 2 h of warm reperfusion, livers in the IGL2-MPS group showed no significant differences in transaminase release (aspartate aminotransferase: 65.58 versus 104.9 UI/L/100 g liver; P = 0.178), lactate clearance, and histological IRI compared with livers in the MPS group. There were no significant differences in biliary acid composition, bile production, and histological biliary IRI. Mitochondrial and endothelial damage was also not significantly different and resulted in similar hepatic inflammasome activation. CONCLUSIONS: This preclinical study shows that a novel IGL2 allows for the safe preservation of marginal liver grafts with SCS and HOPE. Hepatic IRI was comparable with the current gold standard of combining 2 different preservation solutions (University of Wisconsin + Belzer MPS). These data pave the way for a phase I first-in-human study and it is a first step toward tailored preservation solutions for machine perfusion of liver grafts.