Emerging recognition of the complement system in hepatic ischemia/reperfusion injury, liver regeneration and recovery...

Hepatic ischemia/reperfusion injury (IRI) is a result of the ischemic cascade and may occur in the settings of liver trauma, resection and transplantation. Components of the complement system have been indicated to be mediators of hepatic IRI and regulators of liver regeneration. As such, their potential to mediate both beneficial and harmful effects render them key targets for therapy. In the present study, the mechanisms of complement mediating hepatic IRI were discussed with a focus on the different functions of complement in hepatic injury and liver recovery, and an explanation for this apparent paradox is provided, i.e. that the complement products C3a and C5a have an important role in liver damage; however, C3a and C5a are also necessary for liver regeneration. Furthermore, situated at the end of the complement activation cascade, the membrane attack complex is crucial in hepatic IRI and inhibiting the complex with a site-targeted murine complement inhibitor, complement receptor 2-CD59, may improve liver regeneration after partial hepatectomy, even when hepatectomy is combined with ischemia and reperfusion.