The World Health Organization reports that thousands of individuals die each year while waiting for donor organs, largely due to shortages of human tissue. In China, hundreds of thousands develop liver failure annually, yet only about 6,000 liver transplants were carried out in 2022. The success of this experimental effort suggests a possible future path for addressing the severe imbalance between organ supply and demand.

Details of the First-in-Human Pig Liver Graft

The patient was a 71-year-old man with hepatitis B-related cirrhosis and hepatocellular carcinoma who did not qualify for surgical removal of his tumors or for a human liver transplant. Surgeons implanted an auxiliary liver graft derived from a genetically modified Diannan miniature pig featuring 10 targeted gene alterations. These included the removal of xenoantigens and the addition of human transgenes designed to improve compatibility with the human immune and coagulation systems.

During the first month after transplantation, the pig liver graft performed well, producing bile and generating coagulation factors without signs of hyperacute or acute rejection. On day 38, however, physicians removed the graft after the patient developed xenotransplantation-associated thrombotic microangiopathy (xTMA), a complication linked to complement activation and injury to blood vessel linings. Treatment with the complement inhibitor eculizumab and plasma exchange resolved the xTMA. The patient later experienced several episodes of upper gastrointestinal bleeding and died on day 171.

Expert Perspectives on the Significance and Challenges

"This case proves that a genetically engineered pig liver can function in a human for an extended period," said lead investigator Beicheng Sun, MD, PhD, Department of Hepatobiliary Surgery, and President of the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. "It is a pivotal step forward, demonstrating both the promise and the remaining hurdles, particularly regarding coagulation dysregulation and immune complications, that must be overcome."

"This report is a landmark in hepatology," noted Heiner Wedemeyer, MD, Co-Editor, Journal of Hepatology, and Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany, in an accompanying editorial. "It shows that a genetically modified porcine liver can engraft and deliver key hepatic functions in a human recipient. At the same time, it highlights the biological and ethical challenges that remain before such approaches can be translated into wider clinical use. Xenotransplantation may open completely new paths for patients with acute liver failure, acute-on-chronic liver failure, and hepatocellular carcinoma. A new era of transplant hepatology has started."

"The publication of this case reaffirms the Journal of Hepatology as the world's leading liver journal. We are committed to presenting cutting-edge translational discoveries that redefine what is possible in hepatology," added Vlad Ratziu, MD, PhD, Editor in Chief, Journal of Hepatology, and Institute for Cardiometabolism and Nutrition, Sorbonne Université and Hospital Pitié Salpêtrière, Paris, France.

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