N-acetylcysteine in Liver Transplantation

This is a randomized, double-blind placebo-controlled study that investigates the use of NAC during and after OLT. A total of 100 patients will be recruited. Fifty will receive a placebo (normal saline) and the other fifty will receive NAC. The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses. The placebo group will receive an equal volume of a normal saline infusion for 13 doses. Both groups will be followed for one year after their OLT. The following data will be recorded and collected: liver function tests, renal function tests, liver graft survival rate, patient survival, serum level of glutathione (GSH-PX/GR), duration of hospital and ICU stay. To evaluate the accuracy of calculated serum creatinine clearance (CSCC) in predicating the renal performance in OLT patients, another two serum markers will be estimated. The 1st one is Cystatin-C and the 2nd is Beta-trace. The data from CSCC, cystatin-C and beta-trace will be compared to find out which is the best marker in between these three tests to predicate the renal function. The data will be recorded daily for the first week after the surgery, then on days 14, 21, 30, 90, 180 and finely at the end of the first year after the OLT. Statistical analysis of the data will be performed at the conclusion of the study period to determine the difference in the outcome and morbidity and mortality between the two groups. Objective and Specific Aims Objectives: * Assess the efficacy of NAC to preserve liver graft function and to improve patient/graft survival following orthotopic liver transplantation. * Assess the efficacy of NAC to preserve kidney function in the patients undergoing OLT. Primary Aims: * Severity of the post reperfusion syndrome (PRS) will be compared in both groups by assessing hemodynamic parameters and the need for vasopressor support in the neohepatic stage. * Liver graft function, the incidence of primary non-function and delayed function in both the treatment and placebo groups, will be assessed with post-operative liver function tests (ALT, AST, serum bilirubin, PT/INR, APTT, lactate, etc). Liver function tests will be assessed at one month, three month, six month and at one year following the OLT. * The duration of ICU and hospital stays will be compared between the two groups. * Survival rate (patient/graft) between the treatment and placebo groups will be compared at 1 month, 3 months, 6 months and 1 year. * Renal function will be compared in the treatment and placebo groups by assessing the following parameters during and after liver transplantation: urine output (ml/24 hours), serum creatinine and BUN, calculated creatinine clearance. * The incidence of postoperative acute renal failure (ARF) and the extent and duration of renal dysfunction will be compared between the treatment and the placebo groups. Secondary Aims: * Investigating the effect of NAC on the endogenous glutathione peroxides/glutathione reductase (GSH-PX/GR) body stores in patients undergoing OLT. * Investigating the effect of NAC on FK506 induced toxicity. * Investigating the accuracy of two new markers for evaluating the renal function and glomerular filtration rate and compare them to CSCC.