Ex Vivo Perfusion of Gene-Edited Porcine Livers in Patients With Severe Hepatic Failure

Condition(s) studied

Investigational drug(s) / intervention(s)

Ex vivo perfusion of six-gene-edited porcine liver: Liver from a six-gene-edited Bama miniature pig (meeting designated pathogen-free standards) perfused extracorporeally using a specialized perfusion platform. The liver is procured using hypothermic preservation (Schüssner's solution and hypertonic citrate-purine solution), transported at 1-6°C, and connected to the patient via internal jugular and femoral venous access. The perfusion maintains physiological temperature and blood flow through the porcine liver while the patient's blood circulates through the graft.

Multi-drug immunosuppressive therapy: Combination immunosuppression including rituximab, tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte immunoglobulin (ATG), etanercept, methylprednisolone, and eculizumab administered according to a standardized protocol to prevent xenogeneic rejection.

Study summary

The goal of this clinical trial is to evaluate whether extracorporeal perfusion using a gene-edited pig liver can significantly improve liver function and serve as a bridge-to-transplant therapy in patients with severe hepatic failure. It will also assess the survival and functionality of the xenogeneic liver and monitor the safety of the procedure. The main questions it aims to answer are:

* Can extracorporeal perfusion with a gene-edited pig liver significantly improve liver function indicators (including biochemical, coagulation, and metabolic parameters) in patients with severe hepatic failure?
* Is the gene-edited pig liver viable and functional during extracorporeal perfusion, as evidenced by bile secretion, adequate blood flow, and acceptable histopathological findings?
* What adverse events occur in participants during and after extracorporeal xenogeneic liver perfusion?

This is a single-arm study without a comparison group. Participants will:

* Undergo screening assessments to confirm eligibility for severe hepatic failure diagnosis
* Receive extracorporeal perfusion with a gene-edited pig liver for up to 14 days (or until transplantation/clinical improvement)
* Receive intensive immunosuppressive therapy including tacrolimus, rituximab, ATG, mycophenolate mofetil, and other medications to prevent rejection Undergo hourly vital sign monitoring and daily blood tests (liver function, renal function, coagulation, inflammatory markers) during the perfusion period
* Have daily abdominal ultrasounds and liver biopsies every other day to assess graft function and rejection

Eligibility

Primary outcome measure(s)

• Change in liver function parameters from baseline — From initiation of perfusion (Day 0) until discontinuation of perfusion, up to 14 days
  Evaluation of changes in key liver function biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), and international normalized ratio (INR) measured daily during extracorporeal perfusion. Success is defined as stabilization or improvement of these parameters compared to baseline, indicating the gene-edited porcine liver can effectively support metabolic functions and serve as a bridge-to-transplant therapy.

Trial sites (1)

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