Therapeutic effect and safety of stem cell therapy for chronic liver disease: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV-related acute-on-chronic liver failure and liver cirrhosis

“…Stem cell transplantation is an alternative option for liver transplantation in HBV-related end-stage liver disease patients [ 19 ]. A large-scale meta-analysis of randomized controlled trials (RCTs) evaluating the therapeutic effects and safety of stem cell therapy for chronic liver disease (CLD) revealed that stem cell therapy is a safe and effective therapeutic option for CLD and that patients with ACLF benefit the most in terms of improved short-term survival rates [ 20 ]. The results of our previous research showed that UCMSCs also have good therapeutic effects for HBV-related ACLF and liver cirrhosis and that their therapeutic effect could be enhanced by prolonging the UCMSC treatment course [ 10 ].…”

The impact of recipient age on the effects of umbilical cord mesenchymal stem cells on HBV- related acute-on-chronic liver failure and liver cirrhosis

“…A large-scale meta-analysis of randomized controlled trials (RCTs) evaluating the therapeutic effects and safety of stem cell therapy for chronic liver disease (CLD) revealed that stem cell therapy is a safe and effective therapeutic option for CLD and that patients with ACLF bene t the most in terms of improved short-term survival rates (20). The results of our previous research showed that UCMSCs also have good therapeutic effects for HBV-related ACLF and liver cirrhosis and that their therapeutic effect could be enhanced by prolonging the UCMSC treatment course (10).…”

New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury

“…It is important to note that the spectrum of etiologies related to these conditions is broad, including viral infections, autoimmune diseases, alcohol abuse and metabolic diseases. Likewise, marked heterogeneity is observed among studies regarding injection dose, cell source, delivery route and study design [ 50 , 51 , 52 ]. Therefore, the conjunction of multiple experimental protocols and the diversity in the etiology of liver diseases may lead to varying results in MSC therapy and derive in selection bias.…”