Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion

TLDR

Normothermic machine perfusion can assess donor liver viability, but no reliable viability parameter has been identified, and ex vivo findings must be confirmed in transplantation or clinical trials. The study aimed to determine whether bile production can discriminate viable from non‑viable livers by evaluating functional performance, biochemical, and histological evidence during ex vivo perfusion. Twelve extended‑criteria donor livers were perfused for 6 h at 37 °C using an oxygenated red‑blood‑cell/plasma solution with pressure‑controlled pulsatile hepatic‑artery and continuous portal perfusion after a median 6.5‑h cold storage. Livers with high bile output (≥30 g in 6 h) showed lower transaminases, potassium, and histologic injury, whereas low bile output (<20 g) was associated with higher transaminases, potassium, bilirubin, bicarbonate, and necrosis, indicating that bile production is a readily assessable biomarker of viability that could identify suitable extended‑criteria livers.

Abstract

Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37°C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.