Autologous BMNC Infusion for Liver Cirrhosis in Children With BA (ABMNCBA)

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

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.

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.

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

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

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