The goal of this Phase I clinical trial is to evaluate the safety and efficacy of combining the QH-1A bioartificial liver device with mesenchymal stem cells（MSCs） for blood purification in treating patients with acute-on-chronic liver failure, and to determine the optimal treatment duration and frequency for Phase II. 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. The main questions this study aims to answer are: * Does the combined therapy improve the 28-day survival rate after the final treatment? * Does the QH-1A device in its HBAL mode consistently achieve the predefined device performance pass rate? * Do patients show significant improvements in their biochemical markers following treatment? * What is the immunogenicity profile of the mesenchymal stem cells used for blood purification? Participants will be screened within 14 days before their first treatment and will be allocated into one of four groups based on treatment duration and frequency: * 4-hour group (3 patients) * 6-hour group (3 patients) * 8-hour group (3 patients) * Multiple-treatment group (6 patients) Treatment will be administered in a sequential escalation-from the 4-hour group up to the multiple-treatment group-based on safety data from a 28-day observation period, which will be reviewed by a Safety Evaluation Committee. In addition, upon referral to the Hepatitis B Health Clinic, participants will receive tailored health education, comprehensive liver function and virological assessments, and an individualized treatment and follow-up plan.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
The 4-hour group treatment session lasts 4 hours (±15 minutes). In the HBAL mode of the combined bioartificial liver device QH-1A, blood is initially filtered to separate the plasma, which is then pumped into a bioreactor. In this study, this bioreactor is uniquely filled with immortalized mesenchymal stem cells (PT-MSCs) optimized for blood purification. These cells are cultured to adhere to the outer surface of hollow fibers within the bioreactor, creating a stable and efficient living interface that continuously secretes bioactive factors such as exosomes.After passing through the bioreactor, the plasma is re-filtered and then returned to the patient's circulation via a dedicated pump.
After the three subjects in the 4-hour group completed their 4-week follow-up, the Safety Evaluation Committee convened a meeting to review the safety data and determine whether to proceed with the recruitment for the 6-hour group.The 6-hour group treatment session lasts 6 hours (±15 minutes).The treatment procedure is identical to that of the 4-hour group.
After the three subjects in the 6-hour group completed their 4-week follow-up, the Safety Evaluation Committee convened a meeting to review the safety data and determine whether to proceed with the recruitment for the 8-hour group. The 8-hour group treatment session lasts 8 hours (±15 minutes).The treatment procedure is identical to that of the 4-hour group.
Subjects in the multiple-treatment group will receive 2-3 sessions of bioartificial liver treatment; the number of sessions will be determined by the investigators based on the subjects' clinical needs. The treatment duration for each session will be set as the maximum tolerable period, as confirmed by the Safety Evaluation Committee based on 28-day safety observations from the 4-hour, 6-hour, and 8-hour groups. Each treatment session is administered following the procedure applied to patients in the group with the optimal tolerability duration.
Third Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
Survival rate
Time frame: 28-day
Combined Bioartificial Liver Device QH-1A Equipment Performance Pass Rate
Pass Criteria: If all items on the trial medical device evaluation are rated as "Yes," the device's performance is deemed acceptable. If any evaluation item is rated as "No," the device's performance is considered unacceptable. Reasons for any "No" ratings must be documented.
Time frame: Day 1
Changes from the baseline in Child-Pugh grade
The Child-Pugh classification evaluation indicators consist of hepatic encephalopathy, ascites, total bilirubin, albumin, and prolonged PT time. The scoring and classification of the severity of Child-Pugh liver diseases are as follows:Grade A is 5 to 6 points. Grade B is 7 to 9 points. Grade C is 10 to 15 points. The higher the score, the worse the liver function.
Time frame: 28-day
Changes from the baseline in COSSH-ACLF IIs
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. 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.
Time frame: 28-day
Changes from the baseline in MELD score
The MELD score (Model for End-Stage Liver Disease) is a scoring system used to assess the urgency of liver transplantation in chronic liver disease patients. The MELD score typically ranges from 6 to 40, with higher scores indicating more severe disease and a greater need for liver transplantation.
Time frame: 28-day
The rate of bridging liver transplantation
Time frame: 28-day
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