N-acetylcysteine Does Not Prevent Hepatorenal Ischaemia-reperfusion Injury in Patients Undergoing Orthotopic Liver Transplantation

Background: Glutathione (GSH) acts as a free radical scavenger that may be helpful in preventing reperfusion injury. N-acetylcysteine (NAC) replenishes GSH stores. The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury (AKI).

Methods: Our study was a randomized, double-blind, placebo-controlled trial of 100 patients; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous (IV) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses. Both groups were followed up for 1 year post-orthotopic liver transplant (OLT). We recorded liver function tests, renal function tests, graft survival, patient survival, plasma GSH and duration of hospital and ICU stay. In addition to serum creatinine (SCr) levels, we analysed cystatin C and beta-trace as independent measures of glomerular filtration. All clinical data were recorded daily for the first week after the surgery, then on Days 14, 21, 30, 90 and 180 and at the end of the first year.

Results: IV NAC did not affect survival, graft function or risk of AKI. However, GSH levels were highly variable with only 50% of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased. Additional risk factors for AKI in the post-transplant period were female gender (P = 0.05), increased baseline serum bilirubin (P = 0.004) and increased baseline SCr levels (P = 0.02).

Conclusions: IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation. The dose and duration of NAC used, though higher than most renal protection studies, may have been ineffective for raising GSH levels in some patients.