Background
Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool.
Purpose
To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions.
Methods
A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed.
Results
Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs.
Conclusion
Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
Normothermic ex vivo liver machine perfusion (NEVLP) has been developed to address organ shortage in liver transplantation. To establish new therapeutic concepts for the expansion of the donor pool, standardized animal models are needed, that simulate clinical NEVLP. Rat liver grafts were perfused in a dual-vessel NEVLP system using varying doses of the clinically used vasodilator epoprostenol, with and without the addition of the Kupffer cell inhibitor glycine. Cell culture medium supplemented with rat plasma was compared to SteenTM-based perfusion solution, which is used in clinical NEVLP. Perfusion pressures and bile production were recorded, perfusate transaminases levels were measured and tissue was analyzed for cytokines and 8-Isoprostane. Increasing levels of epoprostenol and the addition of glycine resulted in a stepwise decrease of transaminase secretion and improved bile production. SteenTM significantly decreased transaminase secretion as well as IL-1β production, resulting in lowest levels of oxidative stress and best-preserved liver integrity. In conclusion, high doses of epoprostenol seem to ameliorate liver function and prevent cellular damage, with glycine acting synergistically. SteenTM as perfusion basis seems superior. Our rodent NEVLP system may be used to rapidly test new agents for pharmacologic conditioning of livers and to translate these findings from bench-to-bedside.
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