Biliary strictures and liver transplantation : clinical and biomedical aspects

Abstract

The current thesis describes short and long term results of orthotopic liver transplantation (OLT) performed with livers from donation after brain death (DBD) and livers from donation after cardiac death (DCD) with an emphasis on biliary complications, especially nonanastomotic biliary strictures (NAS). In a 20-year single center study we have shown that long term survival has improved significantly with current 1-, 5- and 10-years survival rates of 91%, 83% en 77%, respectively. However, DCD-OLT leads to more development of NAS probably due to more ischemia/reperfusion damage as indicated by higher peaks of alanine aminotransferas (ALT) after OLT. We have shown that peak ALT level of >1300 IU/L was associated with a higher incidence of NAS and can thus be used as a clinical tool. Furthermore, the role of genetic polymorphisms of matrix metalloproteinases (MMPs), as proteolytic enzymes involved in tissue remod eling, was investigated in the relation to the development of biliary stricture formation before, i.e. in primary sclerosing cholangitis (PSC), and after OLT. We have found that MMP-2 C/T polymorphism was related to more severe progression of PSC resulting in earlier OLT or death. In addition, MMP-2 C/T polymorphism was clearly associated with the development of NAS after OLT