A pig liver with eight gene edits supported six macaques with surgically induced liver failure for 74–144 hours outside the body, a preprint reports

A pig liver with eight gene edits supported six macaques with surgically induced liver failure for 74–144 hours outside the body, a preprint reports

Blood from the macaques flowed through a pig liver on a perfusion device and back into their bodies. On 2 November, researchers from Yunnan Agricultural University, two hospitals and True Health Medical, the company that made the device, published a preprint, a manuscript that has not been peer reviewed.

Patients who develop acute liver failure in the setting of cirrhosis need a donor liver within days: in a UK urgent liver transplant programme, 42 of 52 patients received an organ, typically two days after listing, while the remaining ten died, typically within a week. The authors propose connecting patients to a pig liver outside the body to provide protein synthesis and toxin clearance until a donor organ becomes available or their own liver recovers.

The researchers induced liver failure in the macaques surgically. Because removing the entire liver risks bleeding, they instead tied off and cut the hepatic artery and bile duct, then narrowed the portal vein, which carries blood from the intestine to the liver, by about three quarters. The donor pig had eight gene edits: three genes responsible for sugar markers targeted by the recipient's antibodies were inactivated, and five human genes were added. Three of the human genes inhibit complement, a cascade of proteins that destroys foreign cells, and two inhibit clot formation. The macaques received five drugs to suppress their immune systems.

Under the authors' protocol, the pig liver was connected at least 18 hours after surgery and only once the macaque showed at least one of three signs of liver failure: rising ALT and AST (enzymes released by dying liver cells), rising bilirubin (a bile pigment), or slower blood clotting. The first experiment tested the device, the second began before signs of liver failure appeared, and the remaining four followed the protocol. The livers remained connected for 74, 98, 84, 110, 144 and 101 hours, after which the animals were euthanised. All six livers produced bile, although two were producing very little by the end of the experiment. ALT and AST initially rose and began to fall 24–48 hours after connection; blood clotting generally improved, and the rise in bilirubin slowed.

Platelet counts fell severalfold in every macaque after connection and did not recover; interleukin-6, an inflammatory signal, also rose in all animals. By the end of the experiments, three of the six donor livers had moderate or severe injury, and three had mild injury. The authors attribute the fall in platelet counts to Kupffer cells, immune cells in the pig liver that engulf macaque platelets, and the liver injury to the interruption and restoration of blood flow and to inflammation. They found no evidence of either hyperacute rejection, triggered by antibodies already present in the blood, or acute rejection: the livers had small antibody deposits and no detectable complement. The authors suggest that the eight gene edits together with immunosuppression helped prevent rejection.

Some of the preprint's authors previously transplanted a pig liver inside the body: in the Journal of Hepatology, they described an auxiliary liver transplanted into a living patient at a hospital in Anhui. It functioned for 31 days without hyperacute or acute rejection and was removed on day 38 because of thrombotic microangiopathy, in which blood clots block small vessels. The preprint's authors suggest that support from a liver outside the body can be adjusted and the liver itself disconnected.

Chinese guidelines issued in April 2026 on animal organ transplantation set out criteria for an organ to qualify for human trials. For pig livers used outside the body in monkeys with liver failure, these include at least 72 hours and at least six experiments. The shortest connection lasted 74 hours.