DHOPE in DCD Liver Transplantation
How Oxygenated Machine Perfusion May Improve Long-Term Outcomes in DCD Liver Transplantation
Understanding the Challenge of DCD Liver Transplantation
DHOPE in DCD Liver Transplantation is gaining attention as transplant teams increasingly use extended criteria donor grafts to address organ shortage. Among them, livers donated after circulatory death, known as DCD livers, help expand the pool of transplantable organs. However, these grafts are associated with a higher risk of biliary complications after transplantation. A study published in Annals of Surgery reports the 5-year follow-up of the multicenter randomized DHOPE-DCD trial. This trial compared two preservation strategies for DCD livers before transplantation: dual hypothermic oxygenated machine perfusion, known as DHOPE, and conventional static cold storage.
Why DCD livers carry a specific risk
DCD liver transplantation is associated with an increased risk of nonanastomotic biliary strictures, also known as NAS. These strictures are irregularities or narrowings of the donor bile ducts, excluding the biliary anastomosis. According to the authors, NAS occur about three times more often after DCD liver transplantation than after liver transplantation from donation after brain death. One of the main explanations is ischemia-reperfusion injury, which is linked to the additional period of warm ischemia in DCD donors. These complications can have important consequences for patients. They may lead to cholestasis, jaundice, cholangitis, repeated biliary interventions, retransplantation, or death related to biliary complications.
What is DHOPE?
DHOPE stands for dual hypothermic oxygenated machine perfusion. It is a preservation method in which the liver graft is perfused at low temperature with an oxygenated solution before transplantation. In the DHOPE-DCD trial, end-ischemic DHOPE was performed in the recipient hospital after procurement and conventional static cold storage. Perfusion lasted at least two hours and used an oxygenated machine-perfusion solution. The aim of this approach is to reduce ischemia-reperfusion injury, which plays an important role in post-transplant complications, especially biliary complications.
A multicenter randomized trial with 5-year follow-up
The study included patients receiving DCD liver transplantation in six European centers. Between January 2016 and July 2019, recipients were randomly assigned to one of two groups. The first group received a liver preserved with DHOPE before transplantation. The second group, the control group, received a liver preserved with conventional static cold storage. A total of 156 patients were included: 78 in the machine perfusion group and 78 in the control group. The primary endpoint of this long-term analysis was the incidence of symptomatic NAS at 5 years. Secondary endpoints included acute cellular rejection, graft survival, and patient survival.
Sustained reduction in biliary complications
After 5 years of follow-up, the incidence of symptomatic NAS was significantly lower in the DHOPE group than in the control group: 14% versus 26%. Most cases of NAS developed within the first 12 months after transplantation. After that period, the incidence curves in both groups were almost parallel. This suggests that the protective effect of DHOPE on NAS is mainly observed early after transplantation, while the benefit remains visible at 5 years. The authors also recall that the initial trial results had already shown a reduction in NAS at 6 months: 6% in the DHOPE group versus 18% in the control group. The long-term follow-up therefore confirms that the short-term benefit persists several years after transplantation.
Fewer NAS-related interventions
The study also reports that the cumulative number of NAS-related treatments and interventions was lower in the DHOPE group than in the control group: 81 versus 120. These interventions included antibiotic treatment for cholangitis, endoscopic or percutaneous dilatation and stenting, and retransplantation related to NAS. Retransplantation for NAS was also less frequent in the machine perfusion group, with 3 cases compared with 6 in the control group. Death due to NAS was the same in both groups, with 3 cases in each group.
A potential effect on acute cellular rejection
The study also assessed acute cellular rejection, known as ACR. In the overall population, 7 patients in the DHOPE group experienced ACR, compared with 12 in the control group. This difference was not statistically significant. However, among patients transplanted for immune-mediated liver disease, the rate of ACR was significantly lower in the DHOPE group: 0% versus 32% in the control group. The authors remain cautious about this finding because it is based on a relatively small subgroup of patients. However, they indicate that this observation supports the hypothesis that reducing ischemia-reperfusion injury with hypothermic oxygenated machine perfusion may contribute to a less immunogenic environment in the graft.
No significant difference in 5-year survival
Despite the benefits observed for NAS and for ACR in specific subgroups, the study did not show a significant difference between the two groups in graft survival or patient survival at 5 years. Death-censored graft survival was similar in both groups: 82% in the DHOPE group versus 79% in the control group. Overall patient survival at 5 years was also comparable: 63% in the DHOPE group versus 70% in the control group. The leading causes of death were malignancy, followed by infection or sepsis.
What this study brings to liver graft preservation
This publication shows that the short-term benefits of DHOPE in DCD liver transplantation can persist up to 5 years. The main finding is a significant reduction in symptomatic nonanastomotic biliary strictures, a major complication after DCD liver transplantation. The study also suggests a possible benefit on acute cellular rejection in patients transplanted for immune-mediated liver disease, although this requires confirmation.
The authors conclude that DHOPE is an effective preservation method for DCD liver grafts. However, no significant difference in overall patient survival or graft survival was observed at 5 years. This article summarizes the findings reported by the authors and should be interpreted within the context and limitations of the study.
This article is intended for scientific information purposes only and summarizes the findings reported by the authors. DHOPE is presented here based on the results of this randomized trial and should be interpreted within the context and limitations of the study.
Source
This article is based on the scientific publication:
Long-term Follow-up After Hypothermic Oxygenated Machine Perfusion in DCD Liver Transplantation: Results of a Randomized Controlled Multicenter Trial (DHOPE-DCD), published in Annals of Surgery. DOI: 10.1097/SLA.0000000000006876.
Full article here.
This article is brought to you by IGL as part of its scientific news sharing.