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

Abstract

Original Clinical Science-Liver Background. N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. Objective. To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. Methods. Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized 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 ischemia time and alanine aminotransferase level and graft and patient survival (ID no. 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 ischemia time was longer than 6 h (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 mo and 3 y 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 h, N-acetylcysteine improves postoperative ALT levels.

Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial

“…This led to the recent suggestion to use with caution liver grafts from DBDs with 3 or more ECD features or >33% steatosis and livers from circulatory death donors with any ECD features to reduce short-term graft loss and complication prompted by severe ischemia-reperfusion injury. 14 Different therapeutic strategies have been proposed without any clear outcome difference in terms of graft and patient survivals, nor incidences of early allograft dysfunction. 11 , 14 , 25 Therefore, our current findings are of potential clinical relevance as they point out to a clear benefit in terms of graft survival in the context of organ shortage making mandatory using predominantly donors with extended criteria.…”

“…The most common transplant diagnoses were liver cirrhosis related to hepatitis C virus infection, cirrhosis secondary to nonalcoholic steatohepatitis, and alcoholrelated liver cirrhosis. Recipients in the donor's simvastatin treatment group had a similar Model of End-stage Liver Disease score to the control group (16 [11-17] versus 15 [11][12][13][14][15][16][17][18][19][20][21][22]), but a greater presence of portal thrombosis (4 versus 0) than to those of the control group. There were no differences in immunosuppressive treatment between the groups.…”

Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

“…The use of NAC was also studied in donors during organ procurement. In a randomized controlled trial, Gómez-Gavara et al [63] found no differences in the incidence of EAD between the NAC group and the control group (31% vs. 37.4%). However, in the case of CIT greater than 6 h, the use of NAC was associated with lower ALT activities after transplantation [63].…”

“…In a randomized controlled trial, Gómez-Gavara et al [63] found no differences in the incidence of EAD between the NAC group and the control group (31% vs. 37.4%). However, in the case of CIT greater than 6 h, the use of NAC was associated with lower ALT activities after transplantation [63]. The use of NAC did not reduce the incidence of both EAD and PNF in a randomized trial involving 150 patients undergoing LDLT in India [64].…”

N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis

“…23 Finally, 13 studies with 1121 participants were included in the meta-analysis, of which 550 patients received NAC treatment. 15,[22][23][24][25][26][27][28][29][30][31][32][33] The combined search results are shown in Figure 1.…”