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To evaluate the safety, tolerability, and preliminary efficacy of rectus sheath injection of hepatocyte-like cells in the treatment and prevention of small-for-size syndrome, with the ultimate goal of improving patient survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Small-for-Size Syndrome | Experimental | On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath. Cell quantity: The prespecified therapeutic dose is 1.2×10⁸/kg. To ensure safety, the first patient receives 50% of that dose (0.6×10⁸/kg). After safety confirmation, subsequent patients receive the standard 1.2×10⁸/kg (adjusted based on individual rectus sheath capacity, with actual dose recorded). |
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| High risk of small-for-size syndrome | Experimental | On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath. Cell quantity: The prespecified therapeutic dose is 1.2×10⁸/kg. To ensure safety, the first patient receives 50% of that dose (0.6×10⁸/kg). After safety confirmation, subsequent patients receive the standard 1.2×10⁸/kg (adjusted based on individual rectus sheath capacity, with actual dose recorded). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hepatocyte-like cell administration via rectus sheath intramuscular injection | Drug | On the basis of standard medical therapy, patients will receive an intramuscular injection of CiPS-derived hepatocyte cells into the rectus sheath. Cell quantity: The prespecified therapeutic dose is 1.2×10⁸/kg. To ensure safety, the first patient receives 50% of that dose (0.6×10⁸/kg). After safety confirmation, subsequent patients receive the standard 1.2×10⁸/kg (adjusted based on individual rectus sheath capacity, with actual dose recorded). |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events related to hepatocyte-like cell injection | Defined as all adverse events clearly associated with the injection procedure occurring within 7 days after injection, including puncture-site hematoma, secondary infection, etc. The estimated incidence of injection-related adverse events is no more than 25%. | within 7 days after injection |
| 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. | Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 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. | Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 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. | Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 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. | Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 post-treatment. |
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Inclusion Criteria:
（Acute Liver Failure (ALF) An acute onset of liver failure characterized by hepatic encephalopathy of grade II or higher within 4 weeks, in a patient without pre-existing liver disease.
Acute-on-Chronic Liver Failure (ACLF) A complex clinical syndrome characterized by acute deterioration of liver function, triggered by precipitating events, in patients with underlying chronic liver disease (with or without cirrhosis). It manifests as single or multiple organ failure(s) and is associated with high short-term mortality (28-day mortality rate ≥ 15%).
Chronic Liver Failure (CLF) A state of chronic hepatic decompensation occurring progressively in patients with cirrhosis. It is primarily characterized by recurrent ascites and/or hepatic encephalopathy resulting from progressively declining liver function.
Small-for-Size Syndrome (SFSS) Diagnosis is established according to the International Liver Transplantation Society (ILTS) 2023 guidelines on SFSS.） ② Patients must agree to undergo intramuscular injection of cells into the rectus sheath.
Exclusion Criteria:
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Subjects meeting any of the following criteria will be excluded from the study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Friendship Hospital, Capital Medical University | Beijing | Province | 100050 | China |
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| 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. | Blood samples will be collected at before treatment, 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-treatment. |
| Incidence of short-term adverse events related to the hepatocyte-like cell product | Defined as adverse events clearly associated with the hepatocyte-like cell product occurring within 1 month after injection, including fever, rash, hypotension, allergic reactions, etc. The estimated incidence of short-term adverse events related to the hepatocyte-like cell product is no more than 25%. | within 1 month after injection |
| Incidence, severity, and prognosis of small-for-size syndrome | The incidence, severity grade, and patient prognosis of small-for-size syndrome will be recorded, using patients who did not receive hepatocyte-like cell injection during the same period as historical controls. | Within 3 months after injection |
| Coagulation Function | (including Prothrombin Time [PT], Activated Partial Thromboplastin Time [APTT], International Normalized Ratio [INR], and Prothrombin Time Activity [PTA]). PT and APTT will be measured in seconds, INR will be reported as a ratio, and PTA will be measured as a percentage (%). The outcome will be reported as the change from baseline in each coagulation parameter at each specified time point. | Blood samples will be collected before injection, at 6 hours, 12 hours, and on days 1, 3, 7, 14, as well as at months 1, 2, and 3 post-injection. |
| 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. | Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 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. | Measured at before treatment, and at 1, 3, 6, 12 hours post-treatment, and on days 1, 3, 7, 14, as well as at months 1, 2 and 3 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. | MRI assessments will be performed at baseline (pre-treatment), and at Day 7, 14, Month 1, 2, and 3 post-treatment. |
| 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. | MRI assessments will be performed at baseline (pre-treatment), and at Day 7, 14, Month 1, 2, and 3 post-treatment. |
| 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. | MRI assessments will be performed at baseline (post-transplantation), and at Day 28, Month 3, 6, and 12 post-transplantation. |
| Rectus Sheath Ultrasound Examination | With the subject in a supine position and the abdomen fully exposed, an ultrasound probe is placed along the orientation of the rectus abdominis muscle, performing longitudinal and transverse scans. The thickness of the rectus sheath (vertical distance from the inner edge of the anterior sheath to the anterior edge of the posterior sheath) is measured. After injection of hepatocyte-like cells, the same measurements are repeated at each follow-up time point. Meanwhile, special attention is paid to the presence of any abnormal echoic areas within the rectus sheath (e.g., hematoma, effusion, abnormal cell aggregation, or space-occupying lesions), and their location, size, margins, and internal echo characteristics are recorded. Color Doppler mode is used to assess whether abnormal blood flow signals are present in the injection area. | Before injection, 12 hours post-injection, day 3, day 7 , day 14, and months 1, 2, and 3. |
| Change from baseline in serum levels of tumor markers measured in ng/mL | Including Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA), Cancer Antigen 125 (CA125), Carbohydrate Antigen 19-9 (CA19-9), Total Prostate-Specific Antigen (tPSA), Free Prostate-Specific Antigen (fPSA), Complexed Prostate-Specific Antigen (c-PSA), Carbohydrate Antigen CA242, Carbohydrate Antigen CA724, Carbohydrate Antigen CA50, and Cancer Antigen 15-3 (CA153). For markers specific to males (tPSA, fPSA, c-PSA) or females (CA153), only applicable subjects will be tested. Unit of Measure: ng/mL | Blood samples will be collected before injection, and on days 14, as well as at months 1, 2, and 3 post-injection. |
| Change from baseline in serum levels of tumor markers measured in μg/L | Including Neuron-Specific Enolase (NSE), Cytokeratin 19 Fragment (CYFRA21-1), Squamous Cell Carcinoma Antigen (SCC), and Human Epididymis Protein 4 (HE4). For HE4 (female-specific), only applicable subjects will be tested. Unit of Measure: μg/L | Blood samples collected before injection, and on day 14, as well as at months 1, 2, and 3 post-injection. |
| Incidence of medium-to-long-term adverse events related to the hepatocyte-like cell product | Defined as adverse events clearly associated with the hepatocyte-like cell product occurring between 1 month and 3 months after injection, including non-targeted cell migration, abnormal proliferation, etc. The estimated incidence of medium-to-long-term adverse events related to the hepatocyte-like cell product is no more than 15%. | 1to 3 month after injection |