| Backgroud and Objective: Liver cirrhosis(LC) is a common disease in clinical, which often dead from one or more complications, such as upper gastrointestinal hemorrhage(UGH), Spontaneous bacterial peritonitis(SBP), hepatic encephalopathy, primary hepatic carcinoma(PHC) and hepatorenal syndrome(HRS). According to the studies of 2010 global burden of disease showed that there were more than several millions people died of liver cirrhosis. Liver disease has been one of the leading causes of morbidity and mortality in the world. Recent years, bone marrow mesenchymal stem cells(BM-MSCs) transplantation has been applied to the treatment of liver diseases, but its safty and efficacy were controversy. This study is to understand the efficacy, influence factors and safety.Methods: The studies include two aspects:(1)Meta analysis: The system searched in the Cochrane Library, Med-Line(Pub-Med) and Em-base. Journals were also hand-searched in this field. The retrieval time was from created database to February, 2014. 78 studies which used BM-MSCs in the treatment of any chronic liver disease were included. The control trail used Review Manager 5.1 software for analysis, the data before and after treatment used Meta-Analyst 3.13 software for statistical analysis.(2) The clinical control trails study: LC patients treated with BM-MSCs transplantation plus basic treatment in our hospital during 2007 to 2012 were collected. The control group was conformed to inclusion and exclusion criteria and reasonable basic treatment, matching with propensity scores matching by years, gender and diseases category of the treatment group. The t-test was using to compare biochemical, blood coagulatin function and liver fribrosis indexes between two groups. Single factor analysis and the logistics regression analysis were used to test the influence factors of efficacy and tumorigenesis after transfusion. Using Kaplan-Meier to analysised the 36-months survival rates, recorded the side-effects and complications.Results:(1) Meta analysis: A total of five studies were included in the final analysis. The studies were conducted in China, Iran, Egypt and Brazil. Analysis of pooled data of two controlled studies showed that the differences in scores for the model for end-stage liver disease(MELD) was-1.23 [95%CI:-2.45-(-0.01)],-1.87 [95%CI:-3.16-(-0.58)],-2.01 [95%CI:-3.35-(-0.68)] at 2, 4 and 24 wk, respectively after transfusion. Meta-analysis of the 5 studies showed that the mean improvement in albumin(ALB) levels was-0.28, 2.60, 5.28, 4.39 g/L at the end of 8, 16, 24, and 48 wk, respectively, after transfusion. MELD scores, alanine aminotransferase(ALT), total bilirubin levels(TBIL) and prothrombin times(PTs) were notely improved, after transplantation.(2) The clinical control trails study:① The fatigue rates of LC patients were 43.5% vs. 64.7%、52.3% vs. 66.4% and 49.7% vs. 67.4% in the treatment group and control group at the end of 4, 8, 12 months. The incidence rates of ascites were 35.8% vs. 47.6%、30.6% vs. 43.5%、33.4% vs. 45.9% and 40.2% vs. 47.5% at the end of 2, 4, 8 and 12 months between two groups. The hospitalization times of the second years after transfusion were 37.9 days, which were marlkly lower than the control group.② The efficacy of 4 wks after transplantation showed that prealbumin(PALB) and ALT were significant improve at the first week, TBIL, PTs, and liver fibrosis indexes were markly improve at two week, but the ALB was notely increased at 4 wk. Compared with control group, the PALB, PALB, ALB and PTs were markly improved during 1 to 18 months after transplantation. The TBIL was significance lower than control at first month, and ALT was notely higher than control group at second month,after transfusion. Forether researche showed that the survival rates of the 36 months were no significance(χ2=0.564,P=0.453).③ A total of 4 patients 7 copies biopsy specimens were collected. The results showed that cetokeratin-18(CK18) was little liver cells expression in pre-operatie,and were high expression at 5 wk and 14 month. There was markly fate aways at the end of 22 month, which was similar as pre-operate in liver cells, but CK8 and CK19 were only expressed at 5 wk after transfusion.④ The logistics multiple regression analysis showed that the MELD scores(OR=4.703), international normalized ratio(INR)(OR=3.014), complications(OR=2.134)、creatine(Cr)(OR=1.404)、ALB(OR=1.195), TBIL(OR=1.002) and the HBV-DNA levels after transfusion(OR=1.076) were the risk factors of efficacy. The ROC analysis showed that the cut-off value of the MELD scores, ALB, INR and TBIL were 25 scores, 24.5g/L, 2.1, 95.7μmol/L, respectively. Hierarchical analysis showed that BM-MSCs transplantation can improve the 36 months of the patients when MELD scores were lower than 25.0.⑤ The hepatocarcinogenesis rates of 36 months in two groups were no significant(P=0.516).Conclusions:The BM-MSCs transplantation in the treatment of LC patients was safety.Short-term(1-months)efficacy was favorable,but the efficacy of 36 months just can improve some patients.The proper patients of BM-MSCs treatment were MELD scores<25,serum ALB>24.5g/L,INR<2.1 and TBIL<95.7μmol/L.BM-MSCs did not increase the incidence rates of hepatocellular carcinoma,but this conclusions still need large samples,multi-centers,randomized controlled trials or more higher quality Meta-analysis to confirm it.MELD Model for End-stage Liver Disease score终末期肝病模型评分MRI Magnetic Resonance Imaging核磁共振成像MSCs Mesenchymal Stem Cells间充质干细胞PBS Phosphate Buffered Saline磷酸盐缓冲液PLT Platelets血小板计数PHC Primary Hepatic Carcinoma原发性肝癌PTs Prothrombin Times凝血酶原时间PⅢNP Procollagen typeⅢN-terminalEndopeptidaseⅢ型胶原N端肽ROC Receiver Operating Characteristic Curve受试者工作特征曲线SBP Spontaneous Bacterial Peritonitis自发性腹膜炎TBIL Total Bilirubin总胆红素UGH Upper Gastrointestinal Hemorrhage上消化道出血... |
PDF Full Text Request