To evaluate the safety, tolerability, and preliminary efficacy of intramuscular injection of hepatocyte-like cells into the rectus sheath in patients with liver failure (including acute liver failure, acute-on-chronic liver failure, and chronic liver failure) and small-for-size syndrome, with the ultimate goal of improving survival rates.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath. The method, dose, timing, and treatment course of rectus sheath injection of CiPS-derived hepatocyte cells (adjusted by body weight for adults/adolescents) are set as follows: ① Cell quantity: A dose-escalation design (ranging from 1.6 × 10⁷/kg to 1.7 × 10⁸/kg) will be adopted. Treatment will initiate at the lower dose (1.6 × 10⁷/kg). Upon successful safety review, the dose will be gradually escalated up to a maximum of 1.7 × 10⁸/kg.
Survival Rate
Time frame: 1 year following injection
Adverse Reaction Rate
Adverse reactions related to hepatocyte-like cell injection can be categorized into two types: i) injection-related adverse reactions (such as bleeding and infection), and ii) cell product-related adverse reactions (including but not limited to immune rejection and tumorigenicity).
Time frame: within 1 year following injection
Serum Alanine Aminotransferase (ALT)
ALT levels in U/L will be measured from blood samples. The outcome will be reported as the change from baseline in ALT levels at each specified time point.
Time frame: Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Serum Aspartate Aminotransferase (AST)
AST levels in U/L will be measured from blood samples. The outcome will be reported as the change from baseline in AST levels at each specified time point.
Time frame: Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Serum Total Bilirubin
Total bilirubin levels in mg/dL (or μmol/L) will be measured from blood samples. The outcome will be reported as the change from baseline in total bilirubin levels at each specified time point.
Time frame: Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Serum Direct Bilirubin
Direct bilirubin levels in mg/dL (or μmol/L) will be measured from blood samples. The outcome will be reported as the change from baseline in direct bilirubin levels at each specified time point.
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Time frame: Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Plasma Ammonia
Ammonia levels in μmol/L will be measured from blood samples. The outcome will be reported as the change from baseline in plasma ammonia levels at each specified time point.
Time frame: Blood samples will be collected at before treatment, 8 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Heart Rate
Heart rate will be measured in beats per minute (bpm) in a supine or sitting position after the participant has rested for at least 5 minutes. The outcome will be reported as the change from baseline in heart rate at each specified time point.
Time frame: Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Respiratory Rate
Respiratory rate will be measured in breaths per minute (brpm). The outcome will be reported as the change from baseline in respiratory rate at each specified time point.
Time frame: Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Blood Pressure)
Blood pressure will be measured in millimeters of mercury (mmHg) in a supine or sitting position after the participant has rested for at least 5 minutes.
Time frame: Measured at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Consciousness Level as assessed by Glasgow Coma Scale (GCS)
The level of consciousness will be assessed using the Glasgow Coma Scale (GCS). The GCS total score ranges from 3 to 15, with a lower score indicating a lower level of consciousness. The outcome will be reported as the absolute GCS score and the change from baseline at each specified time point.
Time frame: Assessed at before treatment, and at 0.5, 1, 2, 4, 8, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 3, 6, and 12 post-treatment.
Graft Morphological Stability on T2-weighted Fat-Suppressed (T2W-FS) MRI
The graft site within the left rectus abdominis muscle will be assessed by T2W-FS MRI for morphological stability. The outcome is based on the presence or absence of significant changes in location, shape, and size compared to the baseline (post-engraftment) scan. The absence of mass effect, displacement, or deformation of the surrounding muscle will be documented. Stability in these parameters over time will be considered a favorable outcome, while significant deviation will be reported as an adverse event.
Time frame: MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.
Graft Signal Characteristics on T2-weighted Fat-Suppressed (T2W-FS) MRI
The graft site will be assessed by T2W-FS MRI for signal intensity characteristics. The outcome is based on the signal intensity and pattern (e.g., homogeneous, stippled, nodular) relative to the surrounding normal muscle tissue. A stable or resolving signal pattern without the development of focal, nodular, or mass-like high signal intensity will be considered a favorable outcome. The development of new or evolving high-signal areas suggestive of abnormal growth will be reported.
Time frame: MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.
Absence of Abnormal Fat Deposition on T1-weighted Fat-Suppressed (T1W-FS) MRI
The graft site will be assessed by T1W-FS MRI for the absence of abnormal fat deposition, a key indicator for teratoma formation. The outcome is a binary assessment (Yes/No) of whether the signal intensity of the graft region is isointense to surrounding normal muscle tissue.
Time frame: MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation.