Biliary Atresia
Conditions
Brief summary
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
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.
Interventions
COMBINATION_PRODUCTAutologous BMMC transplantation
One administration of autologous bone marrow mononuclear cells via the hepatic artery
Sponsors
Vinmec Research Institute of Stem Cell and Gene Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Autologous BMMC infusion
Eligibility
Sex/Gender
ALL
Age
2 Months to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and serious adverse events | up to the 12-month period following treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The changes in Liver function using Aspart transaminase | up to the 12-month period following treatment | Using AST (Aspart transaminase) (units: U/L) to measure the changes in liver function. |
| The changes in Liver function using Alanine transaminase | up to the 12-month period following treatment | Using ALT (Alanine transaminase) (units: U/L) to measure the changes in liver function. |
| The changes in cholestasis | up to the 12-month period following treatment | Using Total Bilirubin (units: mg/dL) to measure the changes in cholestasis |
| The changes in level of cirrhosis | up to the 12-month period following treatment | 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 |
| The changes in liver biopsy | up to the 12-month period following treatment | Liver biopsy is a powerful clinical tool to evaluate the changes in the level of cirrhosis. |
| The changes in Liver function using Gamma GT | up to the 12-month period following treatment | Using GGT (Gamma GT) (units: U/L) to measure the changes in liver function. |
Countries
Vietnam
Outcome results
None listed