Biliary Atresia, Kasai Operation, Liver Fibrosis, Liver Function Failure, Stem Cell
Conditions
Keywords
Biliary Atresia, Kasai portoenterostomy, Umbilical cord mesenchymal stem cell, UC-MSC, Liver fibrosis, Regenerative therapy, Double-blind randomized controlled trial
Brief summary
Biliary atresia is a progressive liver disease in infants where liver transplantation is often the only long-term option once cirrhosis develops. However, organ shortages, high costs, risks of graft rejection, and the need for lifelong immunosuppression make transplantation difficult for many families. This double-blind randomized clinical trial evaluates whether injecting umbilical cord-mesenchymal stem cells directly into the liver during Kasai portoenterostomy is safe and effective as an additional treatment. Umbilical cord stem cells have strong anti-inflammatory and anti-fibrotic properties, and they carry a low risk of immune rejection. Patients undergoing the Kasai procedure are randomly assigned to receive either direct intrahepatic stem cell injections or a placebo. Participants are followed for 180 days post-surgery to monitor safety, liver function, and changes in liver stiffness.
Interventions
BIOLOGICALUmbilical Cord-Mesenchymal Stem Cells (UC-MSC)
Intraoperative intraparenchymal injection of umbilical cord-derived mesenchymal stem cells (UC-MSCs) at a dose of 10\^5cells/kg, administered via a 1 mL syringe containing UC-MSCs at a concentration of 10\^5 cells/0.1mL in 0.9% NaCl, distributed across hepatic segments 3, 4, 5, and 6 in both liver lobes
PROCEDUREKasai Portoenterostomy
Standard surgical resection of extrahepatic biliary remnants with a Roux-en-Y portoenterostomy to restore bile drainage in biliary atresia patients
Sponsors
Dr Cipto Mangunkusumo General Hospital
PT. Kimia Farma (Persero) Tbk
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Days to 90 Days
Healthy volunteers
No
Inclusion criteria
* Pediatric patients aged 30 to 90 days. * Suspected biliary atresia based on clinical evaluation and diagnostic workup. * Biliary atresia diagnosis confirmed by intraoperative cholangiography. * Undergoing Kasai portoenterostomy at Cipto Mangunkusumo Hospital. * Written informed consent provided by a parent or legally authorized representative.
Exclusion criteria
* Presence of congenital heart disease. * Diagnosis of Down syndrome. * Diagnoses other than biliary atresia confirmed by intraoperative cholangiography (e.g., choledochal cyst) Drop-out Criteria: \- Subjects will be dropped from the study if they develop postoperative anastomotic leakage
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Bilirubin Level | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Measurement of total bilirubin level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ALT(Alanine Transaminase) Levels | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Hepatocellular injury marker |
| Gamma-glutamyl Transferase (GGT) | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Cholestasis marker |
| Serum Albumin Level | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Marker of liver synthesis function and nutrition status |
| Prothrombin Time (PT), INR | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Coagulation parameter to assess liver synthesis function |
| Complete Blood Count | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Hematology panel including hemoglobin, leukocyte count, platelet count, absolute neutrophil count (ANC), and hematocrit. |
| Direct Bilirubin Level | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Measurement of direct bilirubin level |
| Indirect Bilirubin Level | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Measurement of indirect bilirubin levels |
| Pediatric End-Stage Liver Disease-Creatinine (PELD-Cr) Score | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | The Pediatric End-Stage Liver Disease-Creatinine (PELD-Cr) score is used to assess liver disease severity and estimate mortality risk in pediatric patients with end-stage liver disease. In accordance with Organ Procurement and Transplantation Network (OPTN) policy, the minimum score for this scale is capped at 6 (any calculated laboratory score below 6 is reported as 6), and there is no upper limit or maximum score. Higher PELD-Cr scores indicate greater liver disease severity and a worse clinical prognosis. |
| Jaundice Clearance | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Postoperative jaundice resolution, assessed through clinical evaluation and total/direct serum bilirubin levels. |
| Liver Fibrosis Stages | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Evaluated by measuring liver stiffness via Acoustic Radiation Force Impulse (ARFI) ultrasound, mapped to the METAVIR Fibrosis Staging Scale. The scale ranges from a minimum score of 0 (F0: no fibrosis) to a maximum score of 4 (F4: cirrhosis). Higher scores indicate greater liver fibrosis severity and a worse clinical outcome. |
| Regulatory T-cell (Treg) levels | Post-Operative Day 7 | Regulatory T-cell (Treg) levels as an immunological parameter, measured postoperatively using flow cytometry and reported in standard laboratory units. |
| CD11c Levels | Post-Operative Day 7 | CD11c-positive immune cell marker levels, measured postoperatively via flow cytometry and reported in standard laboratory units. |
| Postoperative Cholangitis Incidence | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Incidence of postoperative cholangitis, diagnosed based on clinical symptoms, physical examination, and supporting diagnostic tests as evaluated by the attending physician. |
| Length of Stay | From the date of surgery until initial hospital discharge or death during the same period of care with the surgery, whichever occurs first (assessed up to 12 months). | Calculated as the number of consecutive days from the date of surgery to the date of initial hospital discharge or in-hospital death during the index hospitalization. Re-admissions following initial discharge are excluded. |
| AST (Aspartate Transaminase) Levels | Baseline, Post-Operative Day 7, Post-Operative Day 30, Post-Operative Day 90, Post-Operative Day 180 | Hepatocellular injury marker |
| All-Cause Mortality | From the date of study enrollment until death, assessed up to 12 months. | Evaluated as the incidence of death from any cause occurring during the study period. Cause of death are verified through electronic medical record documentation, official death certificates, or direct patient/family follow-up contact. |
Countries
Indonesia
Contacts
CONTACTTri Hening Rahayatri, MD, PhD
CONTACTIrene Effendy, MD
PRINCIPAL_INVESTIGATORRadiana Dhewayani Antarianto, MD, M.Biomed, PhD
University of Indonesia, Cipto Mangunkusumo Hospital
PRINCIPAL_INVESTIGATORFatima Safira Alatas, MD, PhD
University of Indonesia, Cipto Mangunkusumo Hospital
Outcome results
None listed