About this trial
Acute liver failure (ALF) refers to a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Liver transplantation is the only curative treatment for this type of end-stage liver disease. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. Therefore, compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EV) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and tolerability of MSC-EV in acute-on-chronic liver failure after liver transplantation.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
aged 18-70 years;
Acute on chronic liver failure-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin [TBil] ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio [INR] ≥ 1.5 or prothrombin activity < 40%), complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination, in patients with previously diagnosed or undiagnosed chronic liver disease; Requiring liver transplantation due to acute on chronic liver failure;
Obtain the patients' consent after informing patients of the purpose and method of the clinical trial;
Disqualifiers
Past history of malignant disease
Active uncontrolled infection;
Combined transplantation
EBV-negative;
Trial design
Parallel
Treatments tested in this trial
MSC-EVs
Biological/Vaccine10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors
Treatment groups
Trial outcomes
Primary outcomes
Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.
Incidence, timing and severity of any clinical complication related to MSC-EV infusion, such as tympanic body temperature, heart rate, mean arterial blood pressure and allergy, as assessed by CTCAE v4.0 .
Aspartate aminotransferase (AST)
Collect clinical results reflecting liver function
Alanine aminotransferase (ALT)
Collect clinical results reflecting liver function
Bilirubin level
Collect clinical results reflecting liver function
Secondary outcomes
Number of survived patients at 1 year after liver transplantation, according to the follow-up results.
Patients who are surviving, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation
Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.
Surviving patients with primary and functional grafts, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation.
Recipient's immune function, as assessed by analysis of immune cell subsets from biopsy or blood samples ,at months 1-6 after liver transplantation.
A series of immune cell subsets will be analyzed, including T cells (CD3+), CD4+ T cells (CD3+ CD4+ lymphocytes), CD8+ T cells (CD3+ CD8+ lymphocytes), naïve CD4+ T cells (CD4+ CD45RAhigh lymphocytes), memory CD4+ T cells (CD4+ CD45RO+ lymphocytes), natural killer (NK) cells (CD3- CD56+ lymphocytes), as well as B cells (CD19+ lymphocytes)
Sponsors and contacts
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