Modified Kasai operation combined with autologous bone marrow mononuclear cell infusion for biliary atresia

To evaluate the safety and outcomes of modified Kasai operation combined with autologous bone marrow mononuclear cell (BMMNC) infusion for biliary atresia (BA).

A matched control study was conducted between January 2015 and December 2021. Ten consecutive children with biliary atresia (BA) who underwent the modified Kasai operation combined with autologous BMMNC infusion (cell therapy group) and ten children who had only the modified Kasai operation (control group) were included in the study. The Kasai operation was performed with two modifications: partial exteriorization of the liver, and encirclement with lateral retraction of two hepatic pedicles to facilitate the removal of fibrotic tissue. Bone marrow was harvested through anterior iliac crest under general anesthesia then a modified Kasai operation was performed. After processing, bone marrow mononuclear cells were infused through the umbilical vein at the end of the operation. Serum bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and prothrombin time were monitored at baseline, six months, twelve months, and the last follow-up (4.5 years) after the operation. In addition, esophagoscopy and liver biopsies were performed on patients whose parents agreed. Mixed-effects analysis was used to evaluate the changes in Pediatric End-Stage Liver Disease (PELD) scores.

There were no intraoperative or postoperative complications related to the operation or cell infusion. The average infused BMMNC and CD34 + cell counts per kg bodyweight were 85.5 ± 56.0 × 10⁶/kg and 10.0 ± 3.6 × 10⁶ for the injection, respectively. Following the intervention, all ten patients in the cell therapy group survived, with a mean follow-up duration of 4.5 ± 0.9 years. Meanwhile, three patients in the control group died due to end-stage liver failure, with a mean follow-up time of 4.3 ± 0.9 years. Liver function of the cell therapy group was maintained or improved after the operation and cell infusion, as assessed by biochemical tests. The disease severity reduced markedly in the CT group compared to the control group, with a significant reduction in PELD scores (p < 0.05).

Autologous BMMNC administration combined with Kasai operation for BA is safe and may maintain or improve liver function in the studied patients.

ClinicalTrials.gov Identifier: NCT05517317 on August 26th, 2022.