Baboon-to-human liver transplantation

• Published in: The Lancet (British edition) Vol. 341; no. 8837; pp. 65 - 71
• Main Authors: Starzl, T.E, Fung, J, Tzakis, A, Todo, S, Demetris, A.J, Marino, I.R, Doyle, H, Zeevi, A, Warty, V, Kusne, S, Rudert, W.A, Trucco, M, Michaels, M
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 09.01.1993; Lancet; Elsevier Limited
• Subjects: Adult; AIDS-Related Opportunistic Infections - complications; AIDS-Related Opportunistic Infections - drug therapy; AIDS/HIV; Animals; Biological and medical sciences; Hepatitis B - complications; Hepatitis, Chronic - blood; Hepatitis, Chronic - surgery; HIV Infections - complications; Humans; Immunologic Techniques; Liver; Liver - pathology; Liver Cirrhosis - surgery; Liver Function Tests; Liver Transplantation - methods; Liver, biliary tract, pancreas, portal circulation, spleen; Male; Medical research; Medical sciences; Papio - blood; Postoperative Care; Postoperative Period; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Transplantation, Heterologous - methods; Transplants & implants; Human; Immunopathology; Hepatic disease; AIDS; Hemopathy; Transplantation; Heterotransplantation; Result; Infection; Case study; Viral hepatitis B; Treatment; Viral disease; Surgery; Digestive diseases
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/0140-6736(93)92553-6

Our ability to control both the cellular and humoral components of xenograft rejection in laboratory experiments, together with an organ shortage that has placed limits on clinical transplantation services, prompted us to undertake a liver transplantation from a baboon to a 35-year-old man with B virus-associated chronic active hepatitis and human immunodeficiency virus infection. Liver replacement was performed according to conventional surgical techniques. Immunosuppression was with the FK 506-prednisone-prostaglandin regimen used routinely for hepatic allotransplantation, to which a daily non-myelotoxic dose of cyclophosphamide was added. During 70 days of survival, there was little evidence of hepatic rejection by biochemical monitoring or histopathological examination. Products of hepatic synthesis, including clotting factors, became those of the baboon liver with no obvious adverse effects. Death followed a cerebral and subarachnoid haemorrhage that was caused by an angioinvasive aspergillus infection. However, the underlying cause of death was widespread biliary sludge that formed in the biliary tree despite a seemingly satisfactory choledochojejunostomy. During life and in necropsy samples, there was evidence of the chimerism that we believe is integral to the acceptance of both xenografts and allografts. Our experience has shown the feasibility of controlling the rejection of the baboon liver xenograft in a human recipient. The biliary stasis that was the beginning of lethal infectious complications may be correctable by modifications of surgical technique. In further trials, the error of over-immunosuppression should be avoidable.