脐带间充质干细胞治疗慢乙肝肝硬化长期疗效分析

Long-term efficacy of human umbilical cord derived-mesenchymal stem cell transplantation for treating patients with HBV-related decompensated cirrhosis

目的采用随机对照双盲的方法观察人脐带间充质干细胞(UC-MSC)治疗对于慢乙肝肝功能失代偿期患者的长期疗效。方法选取河南省人民医院2013年1月至2015年12月收治的慢乙肝肝硬化肝功能失代偿期患者92例,随机分为治疗组和对照组,各46例。治疗组在常规内科治疗的基础上给予脐带间充质干细胞治疗,每月一次,共3次,每次输注细胞量(3~4)×107,对照组给予常规内科治疗和安慰剂治疗(细胞保存液)。比较两组治疗前及治疗后1、3、6、12、18个月临床症状、体征、血清生物化学指标、血常规、凝血功能、腹部彩超、Child-Pugh评分及不良反应等数据。结果两组血清白蛋白及前白蛋白均呈上升趋势,但在UC-MSC治疗后3、6、12、18个月,治疗组明显高于对照组,两组间差异具有统计学意义(P<0.05)。在治疗后12个月治疗组白蛋白及前白蛋白值最高,分别是37.1±3.3、149.3±31.6,与对照组相比差异最为显著,P值分别为0.014、0.015。在治疗后6、12、18个月时两组间凝血酶原时间、Child-Pugh评分差异具有统计学意义(P<0.05),治疗组小于对照组。在UC-MSC治疗后12、18个月两组间胆碱酯酶差异具有统计学意义,P值分别为0.037、0.035,治疗组高于对照组。随访期间,两组谷丙转氨酶、谷草转氨酶、总胆红素、白细胞、血红蛋白及纳差、乏力、腹水、肝性脑病改善的差异不具有统计学意义(P>0.05)。UC-MSC输注时有3例患者出现发热、2例患者出现皮疹,未见严重不良反应发生。结论人脐带间充质干细胞治疗慢乙肝肝功能失代偿期患者能改善患者临床症状、肝脏合成功能、降低Child-Pugh评分,且具有良好的安全性,具有良好的临床应用前景。

Objective A study of randomized double-blind contrast test was performed to investigate the long term efficacy of human umbilical cord-derived mesenchymal stem cells（UC-MSC） as clinical treatment for HBV-related decompensated liver cirrhosis. Methods Totally 92 cases of HBV-related decompensated liver cirrhosis were randomly divided into two groups： experiment group,control group,46 for each group. In the treatment group,patients with HBV-related decompensated were given standard medical treatment combined with a 3-month regimen of UC-MSC at a dose of（3-4） × 10^7 cell. In the control group,patients with HBV-related decompensated were given standard medical treatments combined with similar looking placebos（cell preservation liquid）. We compared the datas of clinical symptoms,signs,serum biochemical indexes,blood routine,coagulation function,abdominal ultrasound,Child-Pugh score and adverse reactions between the two groups before treatment and 1 month,3 months,6 months,12 months and 18 months after treatment. Results Compared with the control group,the group that received the combination UC-MSC treatment showed a significant rise in albumin,prealbumin,cholinesterase and reduced child-pugh scores and prothrombin time during the follow-up period. The value of albumin and proalbumin in treatment group come to the highest after12 months treatment,which was（37. 1 ± 3. 3） and（149. 3 ± 31. 6）,and the differences between the two groups was most significant,the P value was 0. 014 and 0. 015. The difference of cholinesterase between the two groups was statistically significant after 12 and 18 months treatment,the P value was 0. 037 and 0. 035; The value of cholinesterase in the treatment group was higher than that of the control group. However,there was no significant difference between the two groups of patients for levels of alanine aminotransferase,aspartame aminotransferase, total bilirubin, leucocyte,haemoglobin and the improvement of anorexia,weak,ascites and hepatic encephalopathy. Three patients had fever and two cases developed skin rash, and no serious adverse reactions occurred during the UC-MSC infusion.Conclusion UC-MSC treatment could help to improve clinical symptoms and liver function,reduce child-pugh score,and have good security,so UC-MSC treatment has a good prospect of clinical application.