N-Acetylcysteine and Liver Transplant. Advantages of its Administration in Multi-Organ Donors Especially During World-Economical-Crisis. Long-Term Sub-Group Analysis in a Randomized Study.
Finotti, M., et al.Transplantation Proceedings 2025 [record in progress].
Aims
They aim to assess if N-acetylcysteine (NAC) in deceased brain donors, compared with standard donor management provides long term benefit to liver recipients.
Interventions
The control group was standard donor management and liver procurement. The intervention group received systemic NAC Infusion (30 mg/kg - max 3000 mg over 15 minutes) 1 hour before liver donor surgery, with locoregional NAC Infusion (150 mg/kg - max 300 mg/kg estimated liver weight) into the portal vein immediately before cross-clamping.
Participants
140 adult recipients of deceased donor liver transplants, randomized 1:1 (NAC Group: 69 recipients, No NAC Group: 71 recipients). For the subgroups analysis by primary indication for transplant: HCC (n=71), HCV (n=79) and HBV (n=15). Donor characteristics included a notable proportion of marginal donors (median Donor Risk Index ~1.7–1.9).
Outcomes
Primary Outcomes: Five-year overall survival (OS) in the entire cohort, OS, plus recurrence-free survival (RFS) in patients transplanted for HCC, and OS, plus disease recurrence rates in HCV- and HBV-transplanted populations.
Follow-up
5 years posttransplant.
CET Conclusions
The authors present a long-term sub-group analysis of D’Amico et al’s 2013 trial on use of N-acetylcysteine in liver procurement. In essence making this a retrospective cohort analysis of the original prospective RCT. The focus on long-term follow-up for overall survival (OS) in different sub-groups as well as an assessment of cost effectiveness. Overall, across the 5-years, survival was significantly higher in the NAC group (84%) compared with controls (63%; p = 0.0045), suggesting a long-term survival benefit. For the HCC subgroup: NAC recipients with HCC had better 5-year OS (80% vs. 55%; p = 0.04) but relapse free survival (RFS) was similar in both groups. NAC was not an independent predictor of reduced HCC recurrence; macrovascular invasion and MELD score were more important factors. Within the HCV Subgroup, five-year OS was higher in the NAC group. HCV recurrence-related mortality was significantly lower with NAC, supported by competing risk analysis. NAC recipients also showed lower rates of cholestatic fibrosing hepatitis and autoimmune hepatitis on biopsies. There was no significant benefit in the HBV sub-group. In their cost analysis, they surmise an additional cost per recipient for NAC infusion was minimal (~8.8 euros). The NAC group was associated with fewer post-transplant complications, translating into an approximate saving of ~12,000 euros per patient over 5 years, reflecting cost-effectiveness in the centre/ health care system of the study. The design of secondary analyses like these come with some inherent limitations: although the original study was randomised, the current analysis is retrospective and focusing on sub-groups, for which the initial study was not designed or powered, as such there are relatively small subgroups from a single centre. Overall, they do appear to demonstrate NAC to be a low-cost and potentially clinically beneficial addition for liver donors.
Trial registration
ClinicalTrials.gov - NCT01394497