【摘要】：目的:系統(tǒng)評(píng)價(jià)自體骨髓間充質(zhì)干細(xì)胞(Bone marrow mesenchymal stem cells,BMSCs)經(jīng)肝動(dòng)脈移植治療肝硬化失代償期的療效及安全性,以期為肝硬化失代償期的治療提供參考。方法:電子計(jì)算機(jī)檢索近十年數(shù)據(jù)庫(kù),包括萬(wàn)方數(shù)據(jù)庫(kù)(Wan FangDate),重慶維普(VIP),中國(guó)知網(wǎng)(CKNI)三大中文數(shù)據(jù)庫(kù);還有Cochrane Library,PubMed兩大外文數(shù)據(jù)庫(kù)。手工檢索近十年與肝病研究有關(guān)的重要期刊,并根據(jù)研究需要結(jié)合納入排除標(biāo)準(zhǔn)進(jìn)行文獻(xiàn)篩選,運(yùn)用Revman 5.3分析軟件進(jìn)行Meta分析,結(jié)合GRADE評(píng)分進(jìn)行質(zhì)量等級(jí)評(píng)價(jià)。結(jié)果:(1)本次評(píng)價(jià)符合納入要求的期刊文獻(xiàn)共15篇,發(fā)表時(shí)間為2010年-2016年,研究總共納入病例總數(shù)為1040例。納入文章的證據(jù)質(zhì)量評(píng)價(jià)包含3篇“高級(jí)”,8篇“中級(jí)”,4篇“低級(jí)”,主要影響文章質(zhì)量的是隱藏、盲法、手術(shù)與非手術(shù)對(duì)照。總評(píng)價(jià)分析表明自體骨髓干細(xì)胞移植治療肝硬化失代償期的療效優(yōu)于西醫(yī)常規(guī)對(duì)照治療。(2)對(duì)癥狀的改善,腹水好轉(zhuǎn)方面(MD=1.92,95%CI(1.43~2.57)P0.0001)、納差減輕方面(MD=1.77,95%CI(1.41~2.23),P0.00001)、乏力改善方面(MD=1.74,95%CI(1.39~2.17),P0.00001)、腹脹減輕方面(MD=1.86,95%CI(1.45~2.37)P0.00001),干細(xì)胞移植治療組與西醫(yī)常規(guī)對(duì)照組比較具有統(tǒng)計(jì)意義,說(shuō)明自體骨髓干細(xì)胞移植較西醫(yī)常規(guī)治療更明顯改善肝硬化失代償期的癥狀。(3)血清學(xué)指標(biāo)方面,ALB(MD=5.22,95%CI(2.40~8.04),P=0.0003)、ALT(MD=-17.8,95%CI(-30.8~-4.8),P=0.0070.01)、TBIL(MD=-11.77,95%CI(-17.85~-5.7)P=0.00010.01)、PT(MD=-4.33,95%CI(-8.58~-0.08),P=0.05),干細(xì)胞移植治療組與西醫(yī)常規(guī)對(duì)照組比較具有統(tǒng)計(jì)意義,說(shuō)明自體骨髓干細(xì)胞移植治療肝硬化失代償期對(duì)肝臟功能血清學(xué)改善優(yōu)于西醫(yī)常規(guī)對(duì)照治療;但PTA(MD=19.31,95%CI(-2.72~41.34),P=0.090.05)說(shuō)明干細(xì)胞移植治療組與西醫(yī)常規(guī)對(duì)照組對(duì)凝血酶原時(shí)間活動(dòng)度的改善無(wú)統(tǒng)計(jì)意義,療效相當(dāng)。(4)對(duì)肝臟綜合評(píng)分上,Child-Pugh評(píng)分(MD=-1.4,4,95%CI(-1.68~-1.21),P0.00001)、MELD評(píng)分(=-4.50,95%CI(-8.13~-0.86),P=0.020.05),兩評(píng)分表明干細(xì)胞移植治療組與西醫(yī)常規(guī)對(duì)照組比較具有統(tǒng)計(jì)意義,說(shuō)明干細(xì)胞移植治療組患者的MELD評(píng)分比常規(guī)西醫(yī)治療更優(yōu),但樣本量較少,或需要更大樣本量進(jìn)一步證明。(5)不良反應(yīng)方面因缺乏統(tǒng)計(jì)學(xué)意義難評(píng)定,但所納入文獻(xiàn)均顯示不良反應(yīng)少,安全性高。結(jié)論:(1)Meta分析評(píng)價(jià)說(shuō)明干細(xì)胞移植組在臨床癥狀、肝功能、凝血功能、Child-Pugh評(píng)分、MELD評(píng)分的短期療效(1-6個(gè)月)均優(yōu)于對(duì)照組;并且不良反應(yīng)少,安全性高,值得應(yīng)用推廣。(2)我國(guó)大部分進(jìn)行干細(xì)胞移植患者均為病毒性肝炎所致肝硬化,已進(jìn)行或正在進(jìn)行抗病毒治療;患者肝臟功能越好,療效越顯著。(3)對(duì)進(jìn)行自體骨髓干細(xì)胞移植建議如下:采集骨髓量為100-200ml,分離純化后單個(gè)核細(xì)胞數(shù)需達(dá)到108-1010/ml,干細(xì)胞檢測(cè)達(dá)到106-109/ml,保證存活率達(dá)到75%,4℃冷藏不超4小時(shí),術(shù)前可予促肝或G-CSF輔助,肝動(dòng)脈介入移植療效更佳,術(shù)后可結(jié)合中藥或生長(zhǎng)因子等促進(jìn)干細(xì)胞歸巢分化。
[Abstract]:OBJECTIVE: To evaluate the efficacy and safety of autologous bone marrow mesenchymal stem cells (BMSCs) transplantation via hepatic artery in decompensated cirrhosis in order to provide a reference for the treatment of decompensated cirrhosis. Vip (VIP), China Knowledgeable Network (CKNI) three Chinese databases; and Cochrane Library, PubMed two foreign language databases. Hand-searched in the past decade with liver disease research related important journals, and according to research needs combined with inclusion exclusion criteria for literature screening, using Revman 5.3 analysis software for meta-analysis, combined with GRADE score for quality. Results: (1) Fifteen articles were published from 2010 to 2016. The total number of cases included in the study was 1 040. The evaluation of the quality of evidence included three "advanced", "intermediate" and "low" articles. The main factors affecting the quality of the articles were concealment, blindness, surgery and non-hands. Total evaluation showed that the effect of autologous bone marrow stem cell transplantation on decompensated liver cirrhosis was better than that of routine western medicine treatment. (2) Symptom improvement, ascites improvement (MD = 1.92,95% CI (1.43-2.57) P 0 000 1), Na difference alleviation (MD = 1.77,95% CI (1.41-2.23), P 0 000 01), fatigue improvement (MD = 1.74,95% CI (1.39-2.17), P 0 0 0 0 01). In the aspect of reducing abdominal distension (MD = 1.86,95% CI (1.45-2.37) P 0.00001), the treatment group of stem cell transplantation had statistical significance compared with the routine control group of Western medicine, indicating that autologous bone marrow stem cell transplantation could significantly improve the symptoms of decompensated liver cirrhosis compared with the routine treatment of Western medicine. (3) In the aspect of serological indicators, ALB (MD = 5.22,95% CI (2.40-8.04), P = 0.0003, A LT (MD = - 17.8, 95% CI (- 30.8 ~ - 4.8), P = 0.0070.01), TBIL (MD = - 11.77, 95% CI (- 17.85 ~ - 5.7) P = 0.00010.01), PT (MD = - 4.33, 95% CI (- 8.58 ~ - 0.08), P = 0.05), stem cell transplantation treatment group compared with conventional Western medicine control group has statistical significance, indicating that autologous bone marrow stem cell transplantation for decompensated liver cirrhosis has better serological improvement than the conventional control group. However, PTA (MD = 19.31, 95% CI (-2.72-41.34), P = 0.090.05) showed that the improvement of prothrombin time activity in the stem cell transplantation group was not statistically significant compared with that in the control group. (4) Child-Pugh score (MD =-1.4, 4, 95% CI (-1.68-1.21), P 0.00001, MELD score (=-4.50, 95% C-95% C-1.21) was the same in the comprehensive liver score. I (- 8.13 ~ - 0.86), P = 0.020.05), the two scores showed that the stem cell transplantation treatment group compared with the conventional control group of Western medicine has statistical significance, indicating that the MELD score of stem cell transplantation treatment group is better than the conventional Western medicine treatment, but the sample size is smaller, or need a larger sample size to further prove. (5) Adverse reactions due to lack of statistical significance is difficult. Conclusion: (1) Meta-analysis showed that the short-term efficacy of stem cell transplantation group in clinical symptoms, liver function, coagulation function, Child-Pugh score and MELD score (1-6 months) were better than that of the control group; moreover, it had less adverse reactions and high safety, and was worth popularizing in China. (2) Most of the stem cell transplantation group were improved. Stem cell transplantation patients are all cirrhosis caused by viral hepatitis, have been or are undergoing antiviral treatment; the better the liver function, the more significant the effect. (3) For autologous bone marrow stem cell transplantation recommendations are as follows: the amount of bone marrow collected is 100-200 ml, the number of mononuclear cells after isolation and purification must reach 108-1010/ml, stem cell detection reaches 10. 6-109/ml, the survival rate was 75%. The cryopreserved temperature was not more than 4 hours. Hepatic stimulation or G-CSF could be used before operation. Hepatic artery interventional transplantation was more effective. After operation, the stem cells could be homing and differentiated by combining traditional Chinese medicine or growth factor.
【學(xué)位授予單位】：廣西中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575.2

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