Liver transplantation : chimerism, complications and matrix metalloproteinases

Abstract

Chimerism after orthotopic liver transplantation (OLT) is the main focus of the studies described in this thesis. The first study showed that chimerism of different cell lineages within the liver graft does occur after OLT. Subsequently, in allogeneic blood stem cell recipients, chimerism was demonstrated in liver tissue, providing evidence that circulating progenitor cells can indeed differentiate into parenchymal liver cells.The secondary focus of this thesis is on matrix metalloproteinases (MMPs). These proteolytic enzymes are involved in a wide variety of physiological and disease-related matrix remodeling processes. MMP-2 and MMP-9 gene promotor polymorphisms were assessed of OLT donors and recipients in relation to ischemia/reperfusion injury, acute rejection and non-anastomotic biliary strictures after transplantation. We performed a side study, in which we evaluated the value of serum liver chemistry profile and abdominal ultrasound for detecting clinically relevant biliary strictures using time-dependent multivariate regression analysis. The two main themes, chimerism and MMPs, merge in the final chapter of this thesis. In liver transplant recipients with donor/recipient mismatches for MMP gene polymorphisms chimerism was studied, in both liver biopsies as in peripheral blood after OLT.