干细胞治疗终末期肝病疗效及安全性系统评价

摘要

目的：系统评价干细胞治疗终末期肝病的疗效及安全性。方法采用Cochrane系统评价方法，检索Cochrane图书馆临床对照试验数据库、CNKI、EMbase、CBM、PubMed、万方数据库等电子资料库以及中文科技期刊数据库VIP。由2名评价者共同评价所纳入研究的质量，对同质研究进行Meta分析。结果共纳入11个研究、468例终末期肝病患者。其中3篇文献采用随机数字法分组并实施盲法，其余8篇文献未描述具体随机方法、未实施盲法。2篇文献采用信封分配隐藏方法，其余文献均未描述分配隐藏方法。按观察指标和观察时间进行亚组分析：①在降低Meld评分方面：治疗1个月、3个月、6个月后干细胞治疗组优于对照组，差异有统计学意义[WMD=-1.65，95%CI（-2.95，-0.35）；WMD =-2.54，95%CI（-3.85，-1.23）；WMD =-2.76，95%CI（-4.11，-1.40）]；而治疗12个月时治疗组与对照组差异无统计学意义[WMD =0.20，95%CI（-1.76，2.16）]。②在降低Child-Pugh分级方面：治疗1个月、6个月时干细胞治疗组均优于对照组，差异有统计学意义[WMD =-2.0，95%CI （-2.55，-1.45）；WMD =-0.90，95%CI（-1.39，-0.41）]。治疗3个月、12个月时干细胞治疗组与对照组差异无统计学意义[WMD =0.20，95%CI（-1.48，1.88）；WMD =0.60，95%CI（-0.93，2.13）]。③在血清白蛋白升高方面：治疗1个月时，治疗组均优于对照组，差异均有统计学意义；治疗3个月时，2项研究显示治疗组优于对照组，1项研究显示对照组优于治疗组，差异均有统计学意义；治疗6个月时治疗组优于对照组，差异均有统计学意义；治疗12个月时，1项研究显示治疗组与对照组差异无统计学意义；1项研究对照组优于干细胞组，差异有统计学意义。④血清胆红素降低量：疗程1个月、3个月时，治疗组均优于对照组，差异均有统计学意义；治疗6个月、12个月时治疗组与对照组无统计学差异。⑤血清ALT降低量的变化：治疗1个月时2项研究显示治疗组优于对照组，差异有统计学意义，1项研究治疗组与对照组无统计学差异；3个月、6个月、12个月时均显示治疗组与对照组无统计学意义。⑥在生存率方面：治疗10周及6个月时研究显示干细胞治疗组优于对照组，差异均有统计学意义。结论现有研究显示，干细胞对终末期肝病患者的Child评分、Meld评分、血清白蛋白、血清胆红素、ALT有改善，且能改善患者的临床症状、提高患者短期的生存率，无严重不良反应，但其远期疗效及生存预后尚不确定，尚需更大量的文献进一步的研究报道。%Objective To review the effect and safety of stem cell therapy in treatment of patients with end-stage liver diseases systematicly. Methods Articles were searched from the Cochrane Database of Controlled Trials Register (CCTR), PubMed, EMBASE, the Chinese Biomedical Database (CBM), CNKI, Chinese Scientiifc and Technological Journal Database (VIP database) and Wanfang Database. Quality assessment and data extraction were conducted by two reviewers independently, and disagreement, if any, was resolved by discussion. Meta-analysis was performed for homogeneous studies. Results Total of 11 studies including 468 patients met the inclusion criteria were enrolled in our systematic review. Three studies were grouped by a randomly number count and performed blindly, other eight studies did not describe the detail randomized methods. Two studies performed the envelope allocation methods, other studies did not enforce allocation concealment and none of the trials performed blinding. Subgroup analysis were conducted based on the indexes measured and interventions:①In terms of reducing Meld, the stem cell therapy group was more effective than the control group after treating for 1 month, 3 months and 6 months [WMD=-1.65, 95%CI (-2.95,-0.35);WMD=-2.54, 95%CI (-3.85,-1.23);WMD=-2.76, 95%CI (-4.11,-1.40)]. No signiifcant differences, however, were found after treating for 12 months [WMD=0.20, 95%CI (-1.76, 2.16)].②In terms of reducing Child-Pugh grade, the stem cell therapy group was more effective than the control group in 1 month and 6 months [WMD=-2.0, 95%CI (-2.55,-1.45);WMD=-0.90, 95%CI (-1.39,-0.41)]. However, no signiifcant differences were found after treating for 3 months and 12 months [WMD=0.20, 95%CI (-1.48, 1.88);WMD=0.60,95%CI (-0.93,2.13)].③In terms of raising serum albumin, the stem cell therapy group was more effective than the control group in 1 month. Two studies showed that therapy group was more effective than the control group and one study showed the opposite results when the course was 3 months, a n d differences among these groups were statistically signiifcant. When the treatment course was 6 months, therapy group was more effective than the control group, and the differences were statistically signiifcant. One study showed no statistical signiifcant difference and one study had statistically signiifcant difference between control and therapy groups when the treatment course was 12 months.④In terms of reducing serum bilirubin, the stem cell therapy group manifested better effective than the control group when the treatment course was 1 month and 3 months and no signiifcant differences were noted when the course was 6 months and 12 months.⑤In terms of reducing ALT, two studies showed the stem cell therapy group was more effective than the control group and one study reported an opposite result. No statistical signiifcance, however, were found in two groups when the course was 3 months, 6 months and 12 months.⑥In terms of raising survival rate, the stem cell therapy group was more effective than the control group when the treatment course was 10 weeks and 6 months. Conclusions Recent researches indicated that stem cell therapy in treatment of end-stage liver disease can improve the Child score, Meld score, serum albumin, serum bilirubin, and ALT levels. In addition, it also can relieve clinical symptoms and improve the short-term survival rate of the patients with no seriously adverse reactions. However, the long-term curative effect and prognosis of survival remain uncertain. More studies were needed for further investigation.