A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation

Abstract

SummaryDonation after cardiac death (DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy (IC). This study aimed to compare outcomes between DCD and donation after brain death (DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify betweenstudy predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers.

Liver Grafts From Donors After Circulatory Death on Regional Perfusion With Extended Warm Ischemia Compared With Donors After Brain Death

“…Early allograft dysfunction (EAD) was defined according to Olthoff et al Postoperative acute kidney injury (AKI) was defined according to the Risk, Injury, Failure, Loss and End‐Stage Kidney Disease criteria, and the need for continuous renal replacement therapy (CRRT) was also considered . Biliary complications included anastomotic and nonanastomotic biliary strictures, bile leaks, cholangitis, biliary casts, and stones requiring intervention or surgery . IC was defined according to O’Neill et al as strictures, irregularities, or dilatations of the intrahepatic or extrahepatic bile ducts .…”

“…One such strategy involves the acceptance of organs from donation after circulatory death (DCD). However, liver grafts that have experienced warm ischemia are associated with an increase in primary nonfunction (PNF) and ischemic cholangiopathy (IC), emphasizing the importance of proper donor management and graft selection …”

First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants

“…25 IC was defined and classified as either multifocal or unifocal intrahepatic strictures without the presence of concomitant hepatic artery thrombosis or arterial complications. 1,26 Each patients chart was reviewed retrospectively for clinical data, liver function tests, and imaging. IC was detected clinically and confirmed by images (endoscopic, percutaneous, or magnetic resonance cholangiography).…”

“…Several reports, however, 1,2 suggest inferior graft survival and increased biliary complications in DCD livers with most concerns for an ischemic cholangiopathy (IC), typically developing within the first 3 to 6 months after OLT. 1 The majority of transplant physicians agree that long periods of donor warm ischemia in DCD donation are responsible for intrahepatic cholangiopathy and graft loss, 2-10 besides additional risk factors including donor age, [5][6][7]11 duration of graft-cold ischemia, 4-6 previous liver transplant, 4,9 recipient age, 9 and recipient body-mass-index. 4,12 Dynamic liver preservation techniques, using perfusion of a variety of solutions at different temperatures, have been proposed to protect or rescue marginal liver grafts, including DCD livers.…”

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

“…Unfortunately, DCD liver grafts have a 3‐fold higher risk of developing nonanastomotic biliary strictures (NAS) after transplantation compared with donation after brain death (DBD) liver grafts. The reported incidence of NAS ranges between 16% and 31% in DCD versus 3%‐13% in DBD liver grafts . This type of biliary complication is regarded as a major complication after DCD liver transplantation because it often requires multiple endoscopic interventions and leads to retransplantation in 16% of patients and death in 6% …”