Complement Activation During Liver Transplantation: Special Emphasis on Patients With Atypical Hemolytic Uremic Syndrome
2011 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 11, no 9, 1885-1895 p.Article in journal (Refereed) Published
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy often caused by mutations in complement factor H (CFH), the main regulator of alternative complement pathway. Because CFH is produced mainly by the liver, combined liver-kidney transplantation is a reasonable option in treatment of patients with severe aHUS. We studied complement activation by monitoring activation markers during liver transplantation in two aHUS patients treated extensively with plasma exchange and nine other liver transplantation patients. After the reperfusion, a clear increase in all the activation markers except C4d was observed indicating that the activation occurs mainly through the alternative pathway. Concentration of SC5b-9 was higher in the hepatic than the portal vein indicating complement activation in the graft. Preoperatively and early during the operation, the aHUS patients showed highest C3d concentrations but otherwise their activation markers were similar to the other patients. In the other patients, correlation was found between perioperative SC5b-9 concentration and postoperative alanine aminotransferase and histological changes. This study explains why supply of normal CFH by extensive plasma exchange is beneficial before combined liver-kidney transplantation of aHUS patients. Also the results suggest that perioperative inhibition of the terminal complement cascade might be beneficial if enhanced complement activation is expected.
Place, publisher, year, edition, pages
2011. Vol. 11, no 9, 1885-1895 p.
Acute liver failure, complement, complement regulation, hemolytic uremic syndrome, hypera-cute rejection, innate immunity, ischemia-reperfusion injury, liver transplantation, primary biliary cirrhosis, primary sclerosing cholangitis
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-158892DOI: 10.1111/j.1600-6143.2011.03612.xISI: 000294360400017OAI: oai:DiVA.org:uu-158892DiVA: diva2:441853