PT-MSCs Exosome Injection in the Treatment of Chronic-to-acute Liver Failure

Single-center, Prospective, Randomized Controlled Study of PT-MSCs Exosome Injection (Code: PT-MSCs-EVS-2023-1) in the Treatment of Chronic-to-acute Liver Failure

The goal of this single-center, prospective, randomized controlled study is to evaluate the safety and efficacy of PT-MSCs Exosome Injection (code: PT-MSCs-EVS-2023-1) in treating patients with acute-on-chronic liver failure (ACLF). As an exploratory study with a small sample size, the primary focus is to observe safety outcomes and preliminary efficacy. The study will enroll patients aged 18 to 65 years who meet the diagnostic criteria for acute-on-chronic liver failure as outlined in the 2024 Chinese Liver Failure Clinical Guidelines and have a COSSH-ACLF II score of less than 7.4.

The main questions this study aims to answer are:

Does the combined therapy improve the 12-week survival rate compared to standard treatment alone? What is the safety profile of the PT-MSCs Exosome Injection (incidence of adverse events and serious adverse events)? Does the treatment improve clinical symptoms (such as fatigue, anorexia, and jaundice) and biochemical markers (liver function, coagulation, inflammation)? Does the treatment improve the 4-week survival rate and reduce the incidence of adverse outcomes (death, treatment abandonment, or liver transplantation)?

Participants will be recruited and screened to ensure eligibility. A total of 20 eligible participants will be randomly allocated into one of two groups in a 1:1 ratio using block randomization:

Control Group (10 patients): Participants will receive standard comprehensive internal medical treatment, including antiviral therapy, hepatoprotective drugs, and symptomatic support. Artificial liver support or liver transplantation may be performed based on the investigator's clinical judgment.

Study Group (10 patients): In addition to the standard treatment received by the control group, participants will receive PT-MSCs Exosomes (2×10^11 particles per dose).

For the Study Group, the exosome injection is diluted in 100 mL of normal saline and administered via intravenous infusion over a period of not less than 2 hours. Treatment is administered once every 3 days (on Day 1, Day 4, Day 7, and Day 10) for a total of 4 doses. All participants will undergo follow-up assessments at specific intervals (Days 4, 7, 10, 13, 28, and 84) to monitor survival, clinical improvement, and safety signals.

Inclusion Criteria:

• Aged 18 to 65 years, regardless of gender.
• Diagnosed with Acute-on-Chronic Liver Failure (ACLF) according to the diagnostic criteria in the "Guidelines for Diagnosis and Treatment of Liver Failure (2024 Edition)."
• COSSH-ACLF II score < 7.4.
• Participants must be fully informed about the study and voluntarily sign a written informed consent form prior to participation.

Exclusion Criteria:

• Patients with chronic liver failure.
• Patients with active bleeding or Disseminated Intravascular Coagulation (DIC) that has not been effectively controlled.
• Known allergy to blood products or any medications/drugs used in the treatment protocol.
• Patients with circulatory failure.
• History of myocardial infarction, cerebral infarction, or cerebral hemorrhage within the past 6 months.
• History of malignancy within the past 5 years (excluding cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Pregnant or lactating women.
• Any other conditions that, in the opinion of the investigator, make the patient unsuitable for participation in the trial.