CLINICAL FEASIBILITY OF LIVING DONOR LIVER TRANSPLANTATION IN PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE: AN INTERNATIONAL MULTICENTER STUDY

초록

Background: Acute-on-chronic liver failure (ACLF) represents a distinct clinical syndrome characterized by acute deterioration of liver function in patients with underlying chronic liver disease, accompanied by extrahepatic organ failures and high mortality. Although liver transplantation is the only life-saving treatment for these patients, the clinical efficacy of living donor liver transplantation (LDLT) in ACLF remains controversial. Purpose: This study aimed to evaluate the clinical feasibility of LDLT in patients with ACLF. Method: This international multicenter retrospective study analyzed 236 ACLF patients who underwent LDLT at six transplant centers within the International Living Donor Liver Transplantation Group between 2013 and 2023. ACLF was defined according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium criteria and graded based on the number of organ failures, evaluating six organ systems: liver, kidney, brain, circulation, coagulation, and respiratory. Result(s): A total of 236 patients were stratified by ACLF grade: ACLF-1 (n=109, 46.2%), ACLF-2 (n=68, 28.8%), and ACLF-3 (n=59, 25.0%). Pre-transplant organ failure rates across all organ systems (liver, kidney, brain, coagulation, circulatory, and respiratory) increased significantly with higher ACLF grade (all P<0.001). Median cumulative organ failure scores were 9 (IQR 8–10), 11 (10–12), and 13 (13–16) for ACLF-1, -2, and -3, respectively. MELD scores also differed significantly: 25 (21–28), 31 (26–35), and 35 (31–40) for ACLF1, -2, and -3, respectively (P<0.001). ABO-incompatible LDLT was performed less in the higher grade of ACLF (13.8% vs. 5.9% vs. 1.7%, P=0.018), and GRWR was comparable between the three groups (1.05 [0.81–1.30] vs. 1.05 [0.87– 1.21] vs. 0.93 [0.83–1.16], P=0.269). Post-transplant major complication rates were comparable across groups (P=0.519). However, infectious complications occurred more frequently in ACLF-3 than in the ACLF-1 and 2 groups (54.2% vs. 38.5% vs. 30.9%, P=0.025). Early allograft dysfunction (25.4% vs. 6.4% vs. 10.3%, P=0.001) and 90-day mortality (20.3% vs. 1.8% vs. 1.5%, P<0.001) were significantly higher in ACLF-3. Multivariate analysis identified ACLF grade 3 (OR 13.66, 95% CI 2.94–63.45, P=0.001), prolonged warm ischemic time ≥30 minutes, and non-right liver grafts as independent risk factors for 90-day mortality. Furthermore, post-transplant 90-day survival decreased with increasing number of organ failures (P=0.003). Five-year survival was significantly lower in ACLF3 compared to ACLF-1 and -2 (65.7% vs. 86.7% vs. 83.7%, P=0.005). Conclusion(s): ACLF grade 3 was associated with significantly worse short- and long-term outcomes than grades 1 and 2. Given the advantage of LDLT in allowing controlled timing, careful patient selection and pre-transplant optimization should be performed with consideration of ACLF grade and associated risk factors.