Liver Transplantation and Ischemia-Reperfusion Injury

Liver transplantation is the definitive treatment for end-stage liver disease but is limited by donor organ availability and the risk of graft dysfunction. A critical contributor to early graft injury is ischaemia-reperfusion injury, in which a period of oxygen deprivation during organ retrieval and preservation is followed by generation of reactive oxygen species and inflammatory mediators on reperfusion. This process damages hepatocytes, impairs microcirculation and may provoke biliary epithelial injury, leading to early allograft dysfunction, cholangiopathy and long-term graft loss. Advances in ex situ organ preservation and in situ perfusion techniques aim to reduce ischaemic insult, enable viability assessment and expand the donor pool by rescuing marginal or donation after circulatory death organs. Parallel research on molecular pathways of oxidative stress and innate immune activation has yielded potential targets for pharmacological intervention. Together, these developments have global significance for improving post-transplant outcomes and widening access to transplantation.

Research from Nature Portfolio

Recent clinical investigation has demonstrated that normothermic machine perfusion allows objective viability testing of livers previously deemed unsuitable. In a prospective trial, high-risk donor livers subjected to ex situ perfusion with oxygenated blood-based solution were assessed on parameters such as lactate clearance and bile chemistry. Over 70 per cent of discarded grafts met predefined metabolic criteria and were successfully transplanted with 100 per cent 90-day patient and graft survival. Although biliary strictures remained a challenge in donation after circulatory death grafts, this approach offers a practical route to increase transplant rates and reduce discard of potentially viable organs.

Liver Transplantation and Ischemia-Reperfusion Injury publication trend

The graph below shows the total number of articles in liver transplantation and ischemia-reperfusion injury across all publications each year (not limited to Nature Index journals).

Technical terms

Ischaemia-reperfusion injury: Tissue damage caused by restoration of blood flow after a period of oxygen deprivation.

Normothermic machine perfusion (NMP): Ex situ preservation method circulating oxygenated, temperature-controlled perfusate through an organ.

Donation after circulatory death (DCD): Organ procurement from donors whose circulation has ceased before retrieval.

Early allograft dysfunction (EAD): Impaired graft function manifesting within the first week post-transplantation.

Ischaemic cholangiopathy: Bile duct injury resulting from insufficient blood supply, leading to strictures and graft loss.

References

1. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nature Communications (2020).
2. Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion. PLOS ONE (2014).
3. In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival. American Journal of Transplantation (2019).
4. Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant. JAMA Surgery (2022).
5. Global Consequences of Liver Ischemia/Reperfusion Injury. Oxidative Medicine and Cellular Longevity (2014).