乌鸦传媒

A patient who underwent transplant with a liver that was preserved for 3 days outside of the body using warm machine perfusion was healthy and leading a normal life at 1 year, according to researchers from Switzerland.

The recipient experienced only minimal graft injury with normal bilirubin levels and a small release of liver enzymes within the first week after receiving the graft via ex situ normothermic preservation (peak alanine transaminase [ALT] 138 UL^-1 and peak aspartate aminotransferase [AST] 309 UL^-1), reported Pierre-Alain Clavien, MD, of University Hospital Zurich, and colleagues.

Endoscopic retrograde cholangiography at 11 months showed "a perfectly preserved intrahepatic biliary tree," with lab tests that quickly normalized after a temporary stent was placed, the authors noted in .

The patient experienced a full liver function recovery, with international normalized ratio returning to normal after 4 days.

"In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where 'close-to-perfect' livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel," Clavien and team wrote.

"We think that this first transplantation success with an ex situ normothermic perfusion preserved organ can open new horizons in the treatment of many liver disorders," they concluded.

"In the transplant community, we feel the urge every day to find a suitable organ for patients with a poor prognosis, and unfortunately there are still many patients dying awaiting an organ," Clavien told 乌鸦传媒. "This has led us to look for new ways to increase the donor pool and give these patients a chance."

Current transplant practices provide a narrow window of opportunity (12 hours) to evaluate, transport, and implant a donor graft, the authors noted.

Their previous preclinical work showed that up to 10 days, but did not transplant the grafts into humans.

For their current report, Clavien and colleagues looked at a liver graft weighing 3.75 lbs obtained on May 19, 2021 from a 29-year-old female donor via a standard procurement protocol with cold flush using an IGL-1 solution. Since the donor had invasive abdominal desmoid fibromatosis with chronic intra-abdominal abscesses, recurrent sepsis caused by multi-resistant bacteria (Candida glabrata, Candida dubliniensis, and Enterococcus faecium) requiring long-term medications and total parenteral nutrition, and a 4-cm tumor of unclear nature in segment 1 of the liver, the graft was discarded by other centers. The recipient was a 62-year-old man with severe portal hypertension, advanced cirrhosis, and recurrent hepatocellular carcinoma.

Baseline histology of the tumor in the graft was consistent with a non-malignant perivascular epithelioid tumor or angiomyolipoma without necrosis. After removal of the tumor and brief cold preservation with low-flow oxygenated perfusion at 6 to 8°C with cannulation of all vessels and the common bile duct, the graft was connected to the Wyss ex situ normothermic perfusion device at 37°C.

The device was primed with a blood-based perfusate targeting a hematocrit of 28-30%, which was supplemented with platelets and additives. After 1 hour of reperfusion, a biopsy showed no evidence of reperfusion injury or syndrome.

Liver function -- as evidenced by factor V synthesis -- continuously improved, from 33% at the start of perfusion to 54% within 24 hours.

During perfusion, broad-spectrum antibiotics were used. After organ recovery, elective surgery was performed with the graft, now weighing 2.87 lbs, within 60 minutes of disconnecting the machine on the fourth day of perfusion.

The liver graft had an immediate lactate clearance and increased bile production, in addition to low release of transaminases, which decreased after 24 hours (peak AST 791 UL^-1 and peak ALT 587 UL^-1).

The recipient developed acute kidney failure requiring short-term hemofiltration, "possibly related to a combination of hypovolemia and nephrotoxicity of one of the antibiotics (vancomycin) and hypoalbuminemia (14 gL^-1)," Clavien and team noted. Five days after surgery, a small anastomotic bile leak developed, which required a stent that was removed after 4 weeks. The patient was discharged 12 days after transplant on a reduced immunosuppressive regimen and returned to all usual activities within 2 months. The number of hepatocytes increased by 2.3-fold from transplant to 6 weeks.

While "this inaugural case demonstrates the potential of preserving livers ex situ for several days," additional research with longer follow-up is needed, Clavien and team noted.

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