PhD ceremony Mr. M.E. Sutton: Studies on injury and repair of donor bile ducts after liver transplantation

PhD ceremony: Mr. M.E. Sutton, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Studies on injury and repair of donor bile ducts after liver transplantation

Promotor(s): prof. R.J. Porte, prof. J.A. Lisman

Faculty: Medical Sciences

Orthotopic liver transplantation (OLT) is a well-accepted treatment option for patients with acute liver failure and end-stage chronic liver disease. An important challenge in OLT is the reduction in the incidence of non-anastomotic biliary strictures (NAS) after OLT. Damage to biliary epithelial cells is thought to play a key role in the development of NAS.

This thesis focuses on the regenerative capacity of bile ducts in response to initial biliary damage. A review of the literature on mechanisms leading to biliary epithelial damage and the development of NAS is given. In addition, we have identified novel risk factors for NAS within two subpopulations of OLT recipients; patients transplanted with a liver obtained after cardiac arrest of the donor (DCD), and patients transplanted for primary sclerosing cholangitis.

Experimental studies described in this thesis indicate that (extrahepatic) bile ducts possess an endogenous regenerative potential, in which the peribiliary glands play a pivotal role after severe biliary damage, as is observed after OLT.

Based on a porcine model, we conclude that hypothermic (10°C) machine perfusion of liver grafts leads to an improved preservation of arterial vessels of the bile duct compared to static cold storage and is associated with a better recovery of bile ducts. In addition, for the first time we provide evidence that bile production is a suitable biomarker to assess hepatic viability of discarded human livers during normothermic (37°C) machine perfusion. The application of such a selection criterion to judge discarded human donor livers could potentially expand the donor pool.