自体骨髓间充质干细胞移植治疗失代偿期肝硬化的临床疗效观察

Efficacy of autologous transplantation of bone marrow derived mesenchymal stem cells in the treatment of decompensated liver cirrhosis

目的探讨自体骨髓间充质干细胞经肝动脉移植治疗肝炎肝硬化失代偿期的安全性及疗效。方法抽取17例失代偿期肝炎肝硬化患者的骨髓200 ml,在体外经分离纯化后得到20 ml干细胞悬液,经肝左动脉介入移植治疗,观察术后临床症状、肝功能指标、血清纤维化指标、T细胞亚群百分比及肝左叶前后径、肝左叶上下径、肝右叶前后径、脾脏大小、门静脉直径、脾静脉直径的变化。结果至第4周,16例(94.1%)患者乏力改善,14例(82.4%)患者食欲增加;随访至1年,12例(70.5%)患者腹水减少或者消失,术后无严重不良反应及严重并发症。术后8周肝功能ALT、AST明显下降(P分别为0.0093、0.0173)。术后12周ALB、CHE明显升高(P分别为0.037、0.041),PT、PTA、FIB 12周时明显改善,差异有统计学意义(P分别为0.034、0.041、0.031),但胆红素移植前后变化无统计学意义。CD3、CD4、CD8 T细胞亚群在1个月、6个月、12个月时的变化较术前无统计学差异(P=0.895)。1年后肝纤维四项(HA、PCⅢ、Ⅳ胶原、LA)变化较术前有统计学意义(P分别为0.016、0.049、0.028、0.021)。从术后1个月时,肝脏左叶前后径较术前变小(P=0.0451),上下径增大(P=0.428),而肝右叶前后径较术前变化无统计学意义;术后6个月门静脉直径、脾静脉直径、脾脏大小术后较术前明显缩小(P分别为0.0324、0.0314、0.0416)。结论经肝左动脉自体骨髓干细胞移植术治疗肝炎肝硬患者安全有效,可明显改善肝脏功能,减轻肝脏纤维化,提高患者生活质量,值得作为肝硬化治疗的一种新途径在临床推广。

Objective To explore the therapeutic efficacy and safety of autologous transplantation of bone marrow （BM） derived mesenehymal stem cells （BMSCs） in the treatment of decompensated liver cirrhosis. Methods Total of 17 patients with decompensated live cirrhosis were enrolled in the study. About 200 ml BM was obtained from each patient to isolate the MSCs. The BMSCS were isolated and purified by the density centrifugation method in our stem cell laboratory. The purified BMSCs （20 ml, suspended in normal saline） were transplanted into the liver via left hepatic artery. The improvement in symptoms, signs, and blood biochemistry were observed. Results Four weeks after transplantation, 16 （94.1%） patients showed improvement in fatigue, 14 （82.4%） patients had better appetite, and for 12 （70.5%） patients, the ascites decreased or disappeared after one year. No serious adverse reactions and serious postoperative complications occurred. There was a significant decrease in the serum levels of ALT and AST 8 weeks after transplantation （P = 0.0093, 0.0173）. Twelve weeks after transplantation, there was significant improvement in the levels of ali3umin （ALB）, cholinesterase （CHE）, prothrombin time （PT）, prothrombin activity （PTA） and fibrinogen （FIB） （P = 0.039, 0.028, 0.034, 0.041, 0.03 l, respectively）. However, no significant changes were found in serum bilirubin level and the percentage of CD3, CD4, and CD8 （P = 0.895）. One year after MSC transplantation, there was a significant improvement in the severity of fibrosis as indicated by improved hepatic fibrosis markers （P = 0.016, 0.049, 0.028, 0.021, respectively）. One months after treatment, there was a decrease in the oblique occipital frontal diameter of the hepatic left lobe, and an increase in the superior inferior diameter of the hepatic left lobe by the ultrasonic examination （P = 0.0451, 0.0428）. However, the oblique occipital frontal diameter of the right hepatic lobe showed no significant changes. Six months after the MSC treatment, there was a significant reduction in the spleen size, spleen vein diameter, and portal vein diameter （P = 0.0324, 0.0314, 0.0416, respectively）. Conelusions Autologous transplantation of BMSCs is a safe and effective approach for the treatment of patients with decompensated liver cirrhosis. Patients receiving autologous BMSCs exhibited marked improvement in liver function, the severity of liver fibrosis, and the overall quality of life.