Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.
Clinical Center for Pediatric Liver Transplantation, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.
Stem Cell Res Ther. 2020 Sep 25;11(1):419. doi: 10.1186/s13287-020-01935-w.
Stem cell therapy is becoming an emerging therapeutic option for chronic liver disease (CLD). However, whether stem cell therapy is more effective than conventional treatment remains questionable. We performed a large-scale meta-analysis of randomized controlled trials (RCTs) to evaluate the therapeutic effects and safety of stem cell therapy for CLD.
We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for the period from inception through March 16, 2020. Primary outcomes were all-cause mortality and adverse events related to stem cell therapy. Secondary outcomes included the model for end-stage liver disease score, total bilirubin, albumin, alanine aminotransferase, prothrombin activity, and international normalized ratio. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model.
Twenty-four RCTs were included and the majority of these studies showed a high risk of bias. The meta-analysis indicated that compared with conventional treatment, stem cell therapy was associated with improved survival and liver function including the model of end-stage liver disease score, total bilirubin, and albumin levels. However, it had no obvious beneficial effects on alanine aminotransferase level, prothrombin activity, and international normalized ratio. Subgroup analyses showed stem cell therapy conferred a short-term survival benefit for patients with acute-on-chronic liver failure (ACLF), a single injection was more effective than multiple injections, hepatic arterial infusion was more effective than intravenous infusion, and bone marrow-derived stem cells were more effective than those derived from the umbilical cord. Thirteen trials reported adverse events related to stem cell therapy, but no serious adverse events were reported.
Stem cell therapy is a safe and effective therapeutic option for CLD, while patients with ACLF benefit the most in terms of improved short-term survival. A single injection administration of bone marrow-derived stem cells via the hepatic artery has superior therapeutic effects.
干细胞治疗正在成为治疗慢性肝病（CLD）的一种新兴治疗选择。然而，干细胞治疗是否比传统治疗更有效仍存在疑问。我们对随机对照试验（RCT）进行了大规模荟萃分析，以评估干细胞治疗 CLD 的治疗效果和安全性。
我们系统地检索了 MEDLINE、EMBASE、Cochrane 中央对照试验注册库（CENTRAL）和 ClinicalTrials.gov 数据库，检索时间从建库至 2020 年 3 月 16 日。主要结局指标是全因死亡率和与干细胞治疗相关的不良事件。次要结局指标包括终末期肝病模型评分、总胆红素、白蛋白、丙氨酸氨基转移酶、凝血酶原活动度和国际标准化比值。使用随机效应模型计算标准化均数差（SMD）和比值比（OR）及其 95%置信区间（CI）。
共纳入 24 项 RCT，其中大多数研究显示存在高偏倚风险。荟萃分析表明，与传统治疗相比，干细胞治疗可改善存活率和肝功能，包括终末期肝病模型评分、总胆红素和白蛋白水平。然而，它对丙氨酸氨基转移酶水平、凝血酶原活动度和国际标准化比值无明显有益影响。亚组分析显示，干细胞治疗可为慢加急性肝衰竭（ACLF）患者带来短期生存获益，单次注射比多次注射更有效，肝动脉输注比静脉输注更有效，骨髓源性干细胞比脐带来源的干细胞更有效。有 13 项试验报告了与干细胞治疗相关的不良事件，但未报告严重不良事件。
干细胞治疗是 CLD 的一种安全有效的治疗选择，而 ACLF 患者在短期生存率提高方面获益最大。单次经肝动脉给予骨髓源性干细胞注射具有更好的治疗效果。
