Different injury of common bile ducts in donation after circulatory vs brain death: histological and immunohistochemical evaluation

Within the model of donation after circulatory death (DCD), a more severe degree of ischaemia-reperfusion injury occurs, that seems to play a role on the pathogenesis of biliary complications. Aim of the study was to assess the bile duct injury in two different models of ischaemia, DCD and donation after brain death (DBD), in liver transplantation. Histological samples of common bile duct retrieved after liver graft reperfusion, before biliary anastomosis, were evaluated. Severity of donor bile duct injury was assessed on the basis of Bili- ary epithelial cell loss, Mural stroma necrosis, Inflammation, Peribili- ary vascular plexus damage, Arteriolonecrosis, Thrombosis, Perilumi- nal and deep peribiliary glands (PBG) damage. Cholangiocyte apoptosis and proliferation in periluminal and deep PBG were evaluated by quantitative TUNEL analysis and PCNA immu- nohistochemical expression. Sixty-two bile duct sample were available for 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 PBG 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 p=0.029; PCNA p=0.029) and deep PBGs (Tunel p=0.002; PCNA p=0.006) from bile duct sample with severe histolog- ical injury. Bile duct samples 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 both on periluminal and deep PBG. This study raises the hypothesis of a correlation between the occurrence of microscopic damage and the development of isch- aemic biliary complications. Study supported by ESOT Grant 2017