Autologous BMNC Infusion for Liver Cirrhosis in Children With BA

Study Overview
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Brief Summary
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To evaluate the safety and early outcomes of autologous bone marrow mononuclear cell (BMMNC) infusion for liver cirrhosis due to biliary atresia (BA) after Kasai operation. An open-label clinical trial was performed from January 2015 to December 2021. 12 children with liver cirrhosis due to BA at the time of Kasai or after Kasai were included. Bone marrow was harvested through anterior iliac crest puncture under general anesthesia. Mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation and then infused into the hepatic artery.

Detailed Description
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Biliary atresia (BA) is a progressive fibro-obliterative cholangiopathy and a fatal disease. Without surgery, children with BA rarely survive beyond three years of age. The reported prevalence of BA ranges from 1 in 9640 to 1 in 19,500 live births. In the past, most children with a non-correctable type of BA died without adequate treatment. Recently, stem cell administration has been applied in adults with liver cirrhosis and has shown promising outcomes. An open-label clinical trial was performed from January 2015 to December 2021. 12 children with liver cirrhosis due to BA at the time of Kasai or after Kasai were included. Bone marrow was harvested through anterior iliac crest puncture under general anesthesia. Mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation and then infused into the hepatic artery. Serum bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and prothrombin time were monitored at baseline, three months, six months and 12 months after the transplantation. Esophagoscopies and liver biopsies were performed in patients whose parents provided consent. This study aimed to evaluate both safety and hepatic function after BMMNC administration in these children.

Official Title
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Autologous Bone Marrow Mononuclear Cell Infusion for Liver Cirrhosis in Children With Biliary Atresia

Conditions
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Biliary Atresia

Intervention / Treatment
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* Combination Product: Autologous BMMC transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children were diagnosed with Liver Cirrhosis Due to biliary atresia after Kasai's operation Two months old or older Patients with a manifestation of cirrhosis after Kasai's operation: hepatomegaly, congestive splenomegaly, elevated liver enzymes, Esophageal Varices (based on Endoscopic Diagnosis), cirrhosis (based on liver biopsy) Exclusion Criteria: Epilepsy Coagulation disorders Allergy to anesthetic agents Severe health conditions such as cancer, failure of heart, lung, liver or kidney Active infections Severe psychiatric disorders

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Autologous BMMC infusion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous BMMC infusion<br>One administration of autologous bone marrow mononuclear cells via the hepatic artery | Combination Product: Autologous BMMC transplantation<br>* One administration of autologous bone marrow mononuclear cells via the hepatic artery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and serious adverse events | To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 1 month, 3 months, 6 months, and 9 months after discharge will be evaluated | up to the 12-month period following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes in cholestasis | Using Total Bilirubin (units: mg/dL) to measure the changes in cholestasis | up to the 12-month period following treatment | 
| The changes in Liver function using Aspart transaminase | Using AST (Aspart transaminase) (units: U/L) to measure the changes in liver function. | up to the 12-month period following treatment | 
| The changes in Liver function using Alanine transaminase | Using ALT (Alanine transaminase) (units: U/L) to measure the changes in liver function. | up to the 12-month period following treatment | 
| The changes in Liver function using Gamma GT | Using GGT (Gamma GT) (units: U/L) to measure the changes in liver function. | up to the 12-month period following treatment | 
| The changes in level of cirrhosis | Using PELD score (according to the suggestion of The Liver and Intestinal Organ Transplantation Committee in 2009). PELD is calculated based on three indicators: albumin (g/dL), bilirubin (units: mg/dL) and INR (international normalized ratio). Formula: PELD = 10 * (0.48 * ln(Serum Bilirubin) + 1.857 * ln(INR) - 0.687 * ln(Albumin) + (0.436 if patient is less than 1 year old) + (0.667 if patient has growth failure). Evaluate the result: If PELD <10: good results If 10 <PELD <15: average results If PELD> 15: bad results | up to the 12-month period following treatment | 
| The changes in liver biopsy | Liver biopsy is a powerful clinical tool to evaluate the changes in the level of cirrhosis. | up to the 12-month period following treatment |