The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial

Abstract

Background knowledge. N-acetylcysteine infusions have been widely used to reduce ischaemia/reperfusion damage to the liver; however convincing evidence of their benefits is lacking. Objective. To perform the largest randomised controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. Methods. Single centre, randomised trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of two hundred and fourteen grafts were transplanted and randomised to the N-acetylcysteine group (n=113) or to the standard protocol without N-acetylcysteine (n=101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischaemia time and alanine aminotransferase level and graft and patient survival (ID#NCT01866644). Results. The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group (p=0.38)). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischaemia time was longer than 6 hours (p=0.0125). Oxidative metabolites (Glutathione/Oxidized glutathione and Ophthalmic Acid) were similar in both groups (p>0.05). Graft and patient survival rates at 12 months and 3 years were similar between groups (p=0.54 and p=0.69, respectively). Conclusions. N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 hours, N-acetylcysteine improves postoperative ALT levels.