Fanny Lebossé

Cirrhosis-associated immune dysfunction (CAID) contributes to poor outcomes after liver transplantation (LT), but pre-transplant immune predictors remain insufficiently defined. We investigated whether pre-transplant whole blood transcriptomic profiling was associated with post-LT outcomes in this exploratory ancillary study of the prospective EDMONHG cohort. Transcriptomic analysis of 26 immune-related genes was performed on 97 LT recipients. PCA and volcano plots identified candidate biomarkers; associations with outcomes were assessed using ROC analyses and Kaplan-Meier estimates with cohort medians as thresholds. PC1 (43.5% of variance) decreased progressively from cACLD to ALF (p < 0.001) and was lower in post-LT infected patients (p = 0.044). Within the first month, 34 patients (35%) developed infections; 7 (7.2%) died within 1 year. Three genes met predefined exploratory criteria (q < 0.10, AUC > 0.65) for infections: GNLY and IL7R were downregulated and IL10 upregulated. Low GNLY or high IL10 expression was associated with reduced 30-day infection-free survival (p = 0.019 and p = 0.013). CIITA, IL10, CD177 and S100A9 showed associations with one-year survival, though results should be treated as exploratory given the limited number of events. Pre-transplant transcriptomics captures CAID severity and identifies candidate gene signatures associated with post-LT outcomes. These hypothesis-generating findings warrant validation in larger multicenter cohorts.

Marie-Charlotte Delignette, M.D., Muzhda Haem Rahimi, Ph.D., Morgane Gossez, Pharm.D., Teresa Antonini, M.D., Arnaud Riff, M.D., Estelle Peronnet, Ph.D., Franck Berthier, Ph.D., Fabienne Venet, Ph.D., Fanny Lebossé, Pharm.D., Ph.D., and Guillaume Monneret, Pharm.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0490

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; 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.