Severe injury of common bile ducts in donation after circulatory death liver transplantation: histological and immunohistochemical evaluation

Introduction Within the model of donation after circulatory death (DCD), a more severe degree of ischaemia-reperfusion injury (IRI) is occurring, that seems to play a role on the pathogenesis of biliary complications. Aim of the study was to assess the bile duct injury occurring in two different models of ischaemia, DCD and donation after brain death (DBD), in liver transplanted grafts. Methods Bile duct injury was evaluated on histological samples of common bile duct retrieved after liver graft reperfusion, before biliary anastomosis. Severity of donor bile duct injury was assessed and scored on the basis of Biliary epithelial cell loss, Mural stroma necrosis, Inflammation, Peribiliary vascular plexus damage, Arteriolonecrosis, Thrombosis, Periluminal and deep peribiliary glands damage. Cholangiocyte apoptosis in periluminal and peribiliary glands was evaluated by quantitative terminal deoxy-nucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) analysis on bile duct sections. Cholangiocyte proliferation was studied in bile duct sections by PCNA immunohistochemical expression. Results Sixty-two patients had the bile duct sample available for histological evaluation (2014-2015). A significantly higher number of DCD patients presented necrosis >50% of the bile duct wall [DCD 14/28 (50%), DBD 9/34 (26.5%) p=0.056], peribiliary vascular plexus damage [DCD 8/28 (29%), DBD 3/34 (9%); p=0.053] and periluminal peribiliary gland damage [DCD 20/28 (71%), DBD 14/34 (41%); p=0.016], defining the occurrence of severe histological injury, that was significantly more frequent in DCD liver transplant patients [15/28 (53.6%)] compared to DBD [7/34 (20.6%)] (p=0.007). A significant increased apoptosis and decreased proliferation was evidenced in both periluminal (Tunel assay p=0.029; PCNA expression p=0.029) and deep PBGs (Tunel assay p=0.002; PCNA expression p=0.006) from bile duct sample with severe histological injury. Discussion This study shows an early picture of microscopic damage at the level of the bile duct soon after reperfusion of liver graft during transplantation. Bile duct samples retrieved from DCD grafts expressed more severe injury at the histological level, defining the new feature of severe histological injury. Bile ducts with severe histological injury showed increased apoptosis and reduced proliferation as evaluated by Tunel assay and PCNA expression, both on periluminal and deep PBG. This study raises the hypothesis of a correlation between the occurrence of microscopic damage and the development of ischaemic biliary complications. This study was supported by the ESOT Grant 2017.