Ex-situ normothermic machine perfusion prevents ischemic cholangiopathy after liver transplantation: A meta-regression analysis

Abstract

Background & aims

Liver transplantation (LT) is the gold standard for end-stage liver disease, but ischemic cholangiopathy (IC) remains a significant complication. Ex-situ normothermic machine perfusion (ESNMP) has emerged as a potential strategy to mitigate ischemic injury. However, the effect of ESNMP on reducing post-LT IC remains controversial. This study aimed to perform an updated meta-analysis to evaluate the impact of ESNMP on IC incidence.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. The literature search included studies from 2015 to 2025 comparing LT outcomes using ESNMP vs. static cold storage (SCS). The primary outcome was the incidence of IC. Risk of bias was assessed using the ROBINS-E tool. Statistical analysis, including random-effects meta-analysis, sensitivity analysis, and meta-regression, was performed to evaluate heterogeneity, potential confounders, and the impact of follow-up duration.

Results

Seventeen studies, including 76,045 patients (4843 ESNMP; 71,202 SCS), were analyzed. No statistically significant difference in IC incidence was found between ESNMP and SCS (1.3 % vs. 0.6 %; RR = 0.68, 95 %CI = 0.41–1.13; P = 0.14). Sensitivity analysis excluding one outlier study revealed a reduction in IC risk with ESNMP (RR = 0.62, 95 %CI = 0.38–1.01; P = 0.054).

Two sub-analyses of studies with ≥12 months of follow-up (RR = 0.51, 95 %CI = 0.26–0.99; P = 0.049) and DCDs (RR = 0.33, 95 %CI = 0.16–0.67; P = 0.002) showed risk reduction. The meta-regression revealed that the back-to-base perfusion approach was associated with the occurrence of IC, with an OR of 1.03 (95 %CI = 1.00–1.07, P = 0.035).

Conclusions

a correlation between ESNMP use and IC reduced risk appears to exist, especially with longer follow-up periods and DCDs, though more high-quality studies are needed to confirm this finding.