A prospective randomized trial of N-acetyl cysteine administration during cold preservation of the donor liver for transplantation

Abstract

Aims: N-acetyl cysteine (NAC), an anti oxidant and a glutathione precursor, is effective in ameliorating liver injury of Tylenol overdose. There is experimental evidence that it also reduces ischemia reperfusion (I/R) injury. This clinical study was undertaken to study the effect of NAC administered in the donor operation.Methods: 22 patients were randomized to receive NAC (IV & Portal flush) or no NAC (Control Group) during donor operation. Peak AST levels and 1-hour postreperfusion biopsies were used to assess I/R injury. Episodes of acute rejection were recorded together with immunosuppressive drug levels.Results: There were 4 exclusions (re-exploration for post-operative hemorrhage x3, OLT for acute liver failure x1). The two groups (n = 9 each) were matched for recipient and donor ages and sex. Viral hepatitis accounted for cirrhosis in 3 patients in NAC Group and 6 patients in Control Group. Statistically, Cold and warm ischemia times were not significantly different as was the use of blood and blood products in both groups. Serum peak AST levels were similar and postreperfusion biopsy showed moderate to severe reperfusion injury in 3 recipients in the NAC Group and 4 in the Control Group. Excluding ones associated with low Tacrolimus levels (n = 4), there were 6 episodes of acute rejection (2-mild, 4-moderate) in the NAC Group and 5 in the Control Group (3-mild,1-moderate, 1-severe).Conclusion: In this pilot study, NAC administered during donor operation did not show a protective effect on I/R injury or on acute cellular rejection.

Keywords

• Ischemia reperfusion injury
• N-acetyl cysteine
• Orthotopic liver transplantation.