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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Participants will receive standard comprehensive internal medical treatment, including antiviral therapy, hepatoprotective drugs, and symptomatic support.
Third Affiliated Hospital, Sun Yat-sen University Guangzhou, Guangdong, China 510630
Guangzhou, Guangdong, China
12-Week Survival Rate
The percentage of participants who are alive at 12 weeks after enrollment.
Time frame: 12 weeks
Changes from the baseline in COSSH-ACLF II score
The Chinese Severe Hepatitis B Study Group (COSSH), based on a multicenter, open-label large cohort study, has established a novel prognostic scoring system for hepatitis B virus (HBV)-ACLF: COSSH-ACLF II s. The COSSH-ACLF II score is calculated as: 1.649×ln(INR) + 0.457×HE grade + 0.425×ln(neutrophils) + 0.396×ln(TBil) + 0.576×ln(urea) + 0.033×age. Theoretically, the score ranges from \~1.0 to \~15.0, though clinically observed values typically fall between 4.5 and 10.0. A score of less than 7.4 indicates a low-risk group, a score between 7.4 and 8.4 indicates a moderate-risk group, and a score greater than 8.4 indicates a high risk of 28- and 90-day mortality.Higher scores indicate greater severity of liver failure and a worse outcome.
Time frame: 12 weeks
Changes from the baseline in Child-Pugh score
The Child-Pugh Score assesses the prognosis of chronic liver disease based on five indicators: hepatic encephalopathy, ascites, total bilirubin, albumin, and PT/INR. The total score ranges from 5 to 15. Higher scores indicate worse liver function. (Classification: Grade A = 5-6 points; Grade B = 7-9 points; Grade C = 10-15 points.)
Time frame: 12-weeks
Change from Baseline in Clinical Symptom Score
Assessment of clinical symptoms including fatigue, anorexia, nausea, jaundice, and level of consciousness. Each symptom is graded on a scale from 0 (absent) to 3(severe). The individual scores are summed to calculate a total symptom score ranging from 0 to 15. Higher scores indicate more severe symptoms.
Time frame: 12 weeks
4-Week Survival Rate
The percentage of participants who are alive at 4 weeks after enrollment
Time frame: 4 weeks
The rate of participants with adverse outcomes at Week 4 and Week 12
The rate of adverse outcomes, defined as death, treatment abandonment, or liver transplantation.
Time frame: 4-week , 12-week
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