Nguyen Thanh Liem, Nguyen Hoang Phuong, Ngo Duy Minh, Ha Thu Hien Thi, Mai Kieu-Anh, Bui Thu Hang, Nguyen Phan Van, Pham Lan Huong, Hoang Duc Minh, Cao Anh Dao Thi
Vinmec Research Institute of Stem Cell and Gene Technology, 458 Minh Khai, Hai Ba Trung District, Hanoi, Vietnam.
Vinmec Times City International Hospital, 458 Minh Khai Street, Hanoi, Vietnam.
Stem Cell Res Ther. 2022 Mar 14;13(1):108. doi: 10.1186/s13287-022-02762-x.
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 2017 to December 2019. Nineteen children with liver cirrhosis due to BA after Kasai operation 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. The same procedure was repeated 6 months later. Serum bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and prothrombin time were monitored at baseline, 3 months, 6 months, and 12 months after the first transplantation. Esophagoscopies and liver biopsies were performed in patients whose parents provided consent. Mixed-effect analysis was used to evaluate the changes in Pediatric End-Stage Liver Disease (PELD) scores.
The average MNC and CD34+ cell counts per kg body weight were 50.1 ± 58.5 × 10/kg and 3.5 ± 2.8 × 10 for the first transplantation and 57.1 ± 42.0 × 10/kg and 3.7 ± 2.7 × 10 for the second transplantation. No severe adverse events associated with the cell therapy were observed in the patients. One patient died 5 months after the first infusion at a provincial hospital due to the rupture of esophageal varices, while 18 patients survived. Liver function was maintained or improved after infusion, as assessed by biochemical tests. The severity of the disease reduced markedly, with a significant reduction in PELD scores.
Autologous BMMNC administration for liver cirrhosis due to BA is safe and may maintain or improve liver function.
ClinicalTrials.gov identifier: NCT03468699. Name of the registry: Vinmec Research Institute of Stem Cell and Gene Technology. https://clinicaltrials.gov/ct2/show/NCT03468699?cond=biliary+atresia&cntry=VN&draw=2&rank=2 . Registered on March 16, 2018. The trial results will also be published according to the CONSORT statement at conferences and reported in peer-reviewed journals.
评估自体骨髓单个核细胞（BMMNC）输注治疗Kasai术后胆道闭锁（BA）所致肝硬化的安全性和早期疗效。
2017年1月至2019年12月进行了一项开放标签的临床试验。纳入19例Kasai术后因BA导致肝硬化的儿童。在全身麻醉下通过髂前上棘穿刺采集骨髓。通过Ficoll梯度离心分离单个核细胞（MNC），然后注入肝动脉。6个月后重复相同操作。在首次移植后的基线、3个月、6个月和12个月监测血清胆红素、白蛋白、丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶和凝血酶原时间。对父母同意的患者进行食管镜检查和肝活检。采用混合效应分析评估儿童终末期肝病（PELD）评分的变化。
首次移植时每千克体重的平均MNC和CD34 +细胞计数分别为50.1±58.5×10/kg和3.5±2.8×10，第二次移植时分别为57.1±42.0×10/kg和3.7±2.7×10。患者中未观察到与细胞治疗相关的严重不良事件。1例患者在首次输注后5个月于省级医院因食管静脉曲张破裂死亡，18例患者存活。通过生化检查评估，输注后肝功能得以维持或改善。疾病严重程度明显降低，PELD评分显著降低。
自体BMMNC治疗BA所致肝硬化是安全的，可能维持或改善肝功能。
ClinicalTrials.gov标识符：NCT03468699。注册机构名称：Vinmec干细胞与基因技术研究所。https://clinicaltrials.gov/ct2/show/NCT03468699?cond=biliary+atresia&cntry=VN&draw=2&rank=2 。于2018年3月16日注册。试验结果也将根据CONSORT声明在会议上发表，并在同行评审期刊上报道。
