On this day in medical history: Baboon-to-human liver transplantation is a medical first

On June 28, 1992, an unnamed patient underwent the first animal-to-human liver transplantation using a liver from a baboon. The patient ultimately died 70 days later, but the surgery was a proving ground of sorts for an experimental immunosuppressant drug called FK506, later renamed tacrolimus.

The patient, a 35-year-old man with a history of hepatitis B (HBV), HIV, and cirrhosis of the liver, went to the University of Pittsburgh, PA, after he was refused liver transplantation elsewhere. As his condition worsened in early 1992, he was hospitalized continuously.¹

Baboon livers were thought at the time to be resistant to HBV infection, and baboon-to-human xenotransplantation was already under discussion by the Institutional Review board of the University of Pittsburgh and some government agencies.

The medical team was led by Thomas Starzl, MD, PhD, and John Fung, MD, PhD, both pioneers in the field of organ transplantation.

The donor was a 15-year-old male baboon obtained from a research organization in Texas. The baboon had the same A blood group as the recipient.

For the procedure, the immunosuppression regimen included FK506, prednisone, and prostaglandin, with the addition of a non-myelotoxic dose of cyclophosphamide.

After transplantation, the patient was eating and walking within 5 days. At the time of the surgery, the donated liver weighed 600 g (1.3 lb); after three weeks, it weighed an estimated 1,555 g (3.42 lb).

The patient was released from the ICU after one month, but he developed several subsequent infections that required treatment with nephrotoxic antibodies. On day 21, he had renal failure, likely due to multidrug toxicity, and dialysis was initiated.

Although the patient died after 70 days, little evidence of hepatic rejection was noted. A contributing factor to the patient’s death was a cerebral and subarachnoid hemorrhage caused by an invasive aspergillus infection. In addition, widespread biliary sludge in the biliary tree had formed despite a seemingly successful choledochojejunostomy (an anastomosis between the common bile duct and the jejunum).

Interestingly, the patient’s serum uric acid levels fell from 481.8 µmol/L to < 30 µmol/L after 45 days, and serum cholesterol levels fell from 2.33 mmol/L to 1.71 mmol/L.

“The fall in serum uric acid and cholesterol concentration postoperatively to the low values that are normal for the baboon was an especially dramatic demonstration of the recreation by the xenograft of its own chemical environment and with no apparent adverse effects,” wrote Dr. Starzl and colleagues in a follow-up study published in The Lancet.¹

Despite a flourish in the 1980s and 1990s, the field of xenotransplantation has quieted in recent years due to fears from known and unknown infectious agents, including retroviruses, which could place the recipients at risk.

However, with the advent of genetic engineering and the ability to insert or remove specific genes anywhere in the genome, the field may be re-entering the clinical conversation.²

References:

1. Starzl TE, et al. Baboon-to-human liver transplantation. Lancet. 1993;341(8837):65-71.
2. Meier RPH, et al. Xenotransplantation: back to the future? Transpl Int. 2018;31(5):465-477.