Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers

Abstract

Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS (before DHOPE; baseline) and after graft reperfusion in the recipient. Histological severity of biliary injury was graded according to an established semiquantitative grading system. Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls. Baseline characteristics and the degree of bile duct injury at baseline (end of SCS) were similar between both groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with baseline. In contrast, in DHOPE-preserved livers, the degree of bile duct injury did not increase after reperfusion. Moreover, there was less injury of deep PBG (P = 0.04) after reperfusion in the DHOPE group compared with controls. In conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation. Liver Transplantation 24 655-664 2018 AASLD.

Figure 1

Degree of injury of the bile ducts of DCD livers treated with DHOPE versus controls after SCS and after reperfusion in the recipient. (A) The degree of mural stroma necrosis increased after reperfusion compared with baseline in the control group (P < 0.001), but not in the DHOPE group. (B) No differences were observed for the degree of injury of the PVP. (C) The periluminal PBG of livers treated with DHOPE demonstrated less injury after reperfusion than in the control group (P = 0.04). Additionally, the injury of the deep PBG in the control group increased after reperfusion compared with baseline (P = 0.02). (D) The deep PBG in the livers treated with DHOPE demonstrated less damage after reperfusion than in the control group (P = 0.04). *P value < 0.05.

Figure 2

Representative histologic examples of periluminal PBG in the common bile duct. (A) Bile duct at baseline of a DCD liver in the DHOPE group. (B) Bile duct after reperfusion of a DCD liver in the DHOPE group. (C) Bile duct at baseline of a DCD liver in the control group. (D) Bile duct after reperfusion of a DCD liver in the control group. The insert represents a higher magnification of the periluminal PBG (400×). Bile ducts of livers preserved with DHOPE displayed significantly less epithelial cell loss of the periluminal PBG, compared with control livers. Original magnification was 200×. Arrows indicate periluminal PBG. *Lumen of the bile duct.

Figure 3

Representative histologic examples of deep PBG in the common bile duct of DCD liver grafts. (A) Bile duct at baseline of a DCD liver in the DHOPE group. (B) Bile duct after reperfusion of a DCD liver in the DHOPE group. (C) Bile duct at baseline of a DCD liver in the control group. (D) Bile duct after reperfusion of a DCD liver in the control group. The insert represents a higher magnification of the deep PBG (400×). Arrows indicate deep PBG. *Lumen of the bile duct. Bile ducts of livers preserved with DHOPE displayed significantly less epithelial cell loss of the deep PBG compared with control livers. Original magnification was 200×.