Use of N-acetylcysteine during liver procurement: A prospective randomized controlled study


  • Francesco D'Amico contributed to the study concept and design, the acquisition and analysis of data, and the supervision of the study and manuscript. Alessandro Vitale contributed to the analysis and interpretation of data, the drafting of the manuscript, and the statistical analysis. Anna Chiara Frigo contributed to the statistical analysis. Umberto Cillo contributed to the analysis and interpretation of data and the supervision of the study. Alessandra Bertacco contributed to the acquisition and analysis of data and the critical revision of the manuscript. Donatella Piovan, Domenico Bassi, Rafael Ramirez Morales, Pasquale Bonsignore, Enrico Gringeri, Michele Valmasoni, Greta Garbo, Enrico Lodo, Francesco Enrico D'Amico, Michele Scopelliti, Amedeo Carraro, Martina Gambato, Alberto Brolese, Giacomo Zanus, and Daniele Neri contributed to the critical revision of the manuscript for important intellectual content and the acquisition of data.

  • Francesco D'Amico had full access to all the data and takes full responsibility for the veracity of the data and the statistical analysis.

  • The present study is registered with, identifier NCT01394497.

  • See Editorial on Page 118

Address reprint requests to Francesco D'Amico, M.D., Ph.D., F.E.B.S., Department of Hepatobiliary Surgery and Liver Transplantation, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy. Telephone: +39 049 821-8624; FAX: +39 049 821-1816; E-mail:


Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14-2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used. Liver Transpl 19:135–144, 2013. © 2012 AASLD.