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

Abstract

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 largefor-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 morbimortality, independent of LFS when defined as a morphologic metric alone.

Comment on Portal Hemodynamics in Liver Transplantation: Do not Shunt The Large-For-Flow!

“…For example, in the aforementioned study by our group, a total of 7 recipients were within the criteria for large-for-flow (median PF after reperfusion: 54.9 mL/min/100g) in addition to presenting a major portosystemic shunt. 2 Perioperative shunt ligation in these 7 recipients allowed for a 1.4 to 2.4× increase in normalized PF reaching a median PF of 80 mL/min/100g. 2 Importantly, none of these grafts were within the large-for-size criteria (graft-recipient weight ratio range: 1.4%–2.4%).…”

“…1 In the following, we would like to highlight an important hemodynamic condition seen in transplantation using whole liver grafts that has not been mentioned in the review, namely large-for-flow. 2 This entity is defined by an impaired postreperfusion portal flow (PF) normalized for graft weight and the published cutoffs range from <65 mL/min/100g to <80 mL/min/100g. 2 – 4 In a recent study from our group including 257 whole graft deceased donor liver transplantations (LTs) with routine perioperative hemodynamic assessment, a total of 16% of the recipients presented with a large-for-flow condition after reperfusion, and the latter was an independent risk factor for graft-related complications including primary nonfunction as well as impaired 90-day recipient survival.…”

“… 2 This entity is defined by an impaired postreperfusion portal flow (PF) normalized for graft weight and the published cutoffs range from <65 mL/min/100g to <80 mL/min/100g. 2 – 4 In a recent study from our group including 257 whole graft deceased donor liver transplantations (LTs) with routine perioperative hemodynamic assessment, a total of 16% of the recipients presented with a large-for-flow condition after reperfusion, and the latter was an independent risk factor for graft-related complications including primary nonfunction as well as impaired 90-day recipient survival. 2 These findings confirm data from previous studies showing a significant impact of large-for-flow on post-LT outcomes.…”

“… 2 – 4 In a recent study from our group including 257 whole graft deceased donor liver transplantations (LTs) with routine perioperative hemodynamic assessment, a total of 16% of the recipients presented with a large-for-flow condition after reperfusion, and the latter was an independent risk factor for graft-related complications including primary nonfunction as well as impaired 90-day recipient survival. 2 These findings confirm data from previous studies showing a significant impact of large-for-flow on post-LT outcomes. 3 – 5 The pathophysiological mechanisms of large-for-flow are related to an overall hypoperfusion of the liver graft given the absence of a major compensatory increase in hepatic artery flow in case of a low PF.…”

“… 6 , 7 Consequently, large-for-flow primarily causes parenchymal injury, translating into a high post-LT transaminase peak and an increased risk for primary dysfunction or nonfunction of the graft. 2 , 3 In contrast, during a small-for-flow condition encountered in partial grafts, there is an arterial hypoperfusion of the graft due to the hepatic arterial buffer response in the presence of an inappropriately elevated PF in relation to the graft weight. 1 This compensatory reduction in arterial flow exposes the recipient to an increased risk of post-LT arterial thrombosis and biliary complications.…”