Evolution of morphological changes in donor livers undergoing normothermic machine perfusion.

Aims: There is a shortage of livers for transplantation in the United Kingdom; despite this, more than a fifth of those retrieved are not transplanted. Normothermic machine perfusion (NMP) allows a functional assessment of marginal organs using biochemical parameters. This study describes the histological changes in livers undergoing NMP.

Methods And Results: A total of 170 biopsies taken pre-NMP, after 4 h of NMP, end-NMP and at implantation from 50 livers undergoing NMP as part of standard local transplant practice were retrospectively reviewed. Thirty-eight per cent had large droplet macrovesicular steatosis pre-NMP, which was associated with reduced organ utilisation, P = 0.096, subsequent extracellular fat and a neutrophilic reaction; 32% had small droplet macrovesicular steatosis pre-NMP suggestive of acute cellular stress, the severity of which was unchanged in 64% during the perfusion period. Those showing at least moderate hepatocellular necrosis at end-NMP were less likely to be transplanted (55 versus 24%, P = 0.0505). Variation in the extent of hepatocyte necrosis was seen between biopsies, with 43% of transplanted cases showing less hepatocyte necrosis at implantation compared to end-NMP and 21% more severe necrosis. Patchy portal inflammation was present in 96% of pre-NMP biopsies, although identifiable duct injury was rare and portal thrombi were not identified. Sinusoidal dilation pre-NMP was more frequent in donation after circulatory death donors, typically persisted during NMP although had improved by implantation in most and had resolved in cases with an early post-transplant biopsy.

Conclusions: Histological changes in NMP livers predominantly comprise donor-derived steatosis, stress-associated small droplet steatosis, retrieval- and procedure-associated sinusoidal dilation and ischaemic injury.