Safety, Tolerability, and Preliminary Efficacy of Hepatocyte-like Cell Injection for the Prevention and Treatment of Small-for-Size Syndrome

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%.

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.

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.

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.

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.

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.

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%.

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.

(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.

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.

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.

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.

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.

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.

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.

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.

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

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

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%.