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Pig Liver Perfusion Treats Liver Failure: World First in China

by Sophie Lin - Technology Editor

In a groundbreaking medical first, Chinese scientists have successfully used a gene-edited pig liver to support the function of a human liver, offering a potential new treatment pathway for end-stage liver disease. The innovative procedure, involving ex vivo perfusion, represents a significant step forward in the field of xenotransplantation and provides a potential “bridge” for patients awaiting full liver transplants.

The treatment, conducted by a team led by Dou Kefeng, an academician of the Chinese Academy of Sciences and director of the Department of Hepatobiliary Surgery at Xijing Hospital, alongside colleagues at Tangdu Hospital, both affiliated with the Air Force Medical University of PLA, involved connecting a six-gene-edited pig liver to a patient suffering from acute-on-chronic liver failure. This approach utilizes an extracorporeal life-support system, differing from traditional liver transplantation by preserving the patient’s native organ while providing crucial support.

The core of the breakthrough lies in the leverage of a pig liver that had undergone genetic modification. The team connected the organ to a normothermic mechanical perfusion device, creating a system where the pig liver could temporarily perform key detoxification, synthetic, and metabolic functions. According to reports, the pig liver demonstrated good perfusion and bile secretion throughout the 66-hour treatment period. Key liver function indicators – including bilirubin levels, transaminases, and prothrombin activity – showed sustained and significant improvement during this time, leading the medical team to conclude the therapy was effective.

Illustration of the treatment of a liver failure patient using ex vivo perfusion with a six-gene-edited pig liver. (Screenshot from the WeChat account of Xijing Hospital)

The Promise of Xenotransplantation

Xenotransplantation, the process of transplanting living cells, tissues or organs from one species to another, has long been considered a potential solution to the critical shortage of human organs available for transplantation. However, significant hurdles, including immune rejection and the risk of transmitting zoonotic diseases, have limited its widespread application. Recent advances in gene-editing technologies, such as CRISPR, have offered new avenues to overcome these challenges by modifying animal organs to build them more compatible with the human immune system. This latest development builds on earlier progress in gene-modified pig-to-human liver xenotransplantation, as reported by Nature.

How the Procedure Worked

The team’s approach involved more than 20 departments within the Air Force Medical University of PLA, highlighting the multidisciplinary nature of the research. The process began with obtaining a liver from a pig genetically engineered with six specific gene edits. This edited liver was then connected to a normothermic mechanical perfusion device – a system that maintains the organ at a normal body temperature and provides oxygen and nutrients – and integrated into a cross-circulation system with the patient’s own liver. This allowed the pig liver to temporarily take over essential liver functions without requiring the removal of the patient’s native organ.

According to the reports, the patient, who suffered from acute-on-chronic liver failure, remained in stable condition following the treatment, with physiological and biochemical indicators approaching normal levels. This suggests the gene-edited pig liver successfully provided the necessary support to allow the patient’s own liver to recover, or at least stabilize.

A New Approach to Organ Support

Dou Kefeng described the preliminary success as a milestone in xenotransplantation, emphasizing the potential of combining “gene-edited organs plus extracorporeal life support” to provide organ function support without the need for complete organ replacement. This approach could be particularly valuable as a bridging therapy for patients awaiting liver transplantation, buying them time and improving their chances of a successful transplant. The technique offers a novel way to address the critical shortage of donor organs and could potentially expand access to life-saving treatment for patients with end-stage liver disease.

The implications of this breakthrough extend beyond liver failure. The principles behind this ex vivo perfusion technique could potentially be applied to other failing organs, offering a new paradigm for organ support, and regeneration. Further research and clinical trials will be crucial to fully evaluate the safety and efficacy of this approach and to determine its long-term impact on the field of transplantation.

What comes next for this research involves continued monitoring of the patient and further refinement of the gene-editing and perfusion techniques. The team will likely focus on expanding the application of this technology to a larger patient cohort and exploring its potential for treating other forms of liver disease. The success of this initial case offers a beacon of hope for the future of xenotransplantation and the development of innovative therapies for organ failure.

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