Antioxidant boosts liver transplant outcomes

Infusion of N-acetylcysteine (NAC) in liver donors can significantly improve the outcome of transplantation, research shows.

Graft function and survival were greater in patients who had received NAC-treated livers than in those receiving untreated livers, which the authors say could help the growing number of recipients given suboptimal livers.

The study, published in Liver Transplantation, included 140 patients who were randomly assigned to receive a graft procured either with an NAC protocol (n=69) or by the standard protocol without NAC (n=71). In the NAC protocol, heart-beating donors received a 15-minute systemic infusion of NAC 30 mg/kg an hour before liver harvesting, as well as a locoregional infusion of NAC 150 mg/kg liver weight into the portal vein just before cross-clamping.

Graft survival rates were 93%, 90%, and 86% at 3, 12, and 24 months, respectively, in the NAC group; these rates were significantly greater than the corresponding rates of 82%, 70%, and 67% observed in the control group.

Twice as many patients died during a median follow-up of 33.4 months in the control group compared with the NAC group (31.0 vs 14.5%). At 24 months, patient survival in the NAC group was 90%, in contrast to 72% among patients in the control group.

Multivariate analyses showed that NAC treatment was associated with a 67% reduction in the risk for graft failure, and a 91% reduction in the risk for death at 3 months, independent of recipient age, severity of liver disease, liver transplant period, or donor risk index.

Notably, the authors found that the statistical difference in early graft failure was almost entirely attributable to five patients in the control group who received suboptimal grafts.

Ischemia/reperfusion injury, which is caused by oxidative stress and cytotoxicity, is a major determinant of graft survival. NAC may help the donor liver to replenish its main endogenous antioxidant, glutathione (GSH), say authors Francesco D'Amico (University Hospital of Padua, Italy) and colleagues.

This may also explain why their protocol, in which NAC is given an hour before liver harvest, is the first to produce positive results, suggesting that previous studies did not allow enough time after infusion for sufficient GSH production.

If used in combination with other protocols, such as optimum donor-recipient matching, the NAC protocol could be a cost-effective strategy to boost graft survival, the authors say.

They conclude: "This harvesting procedure should be used in the context of a multimodal strategy aimed at improving the outcomes of [liver transplantation], increasing the use of suboptimal livers, and extending and standardizing the use of such relevant resources."

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