Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV- related liver failure and liver cirrhosis

Abstract

Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses.Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups.Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course.Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

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

“…The results of previous studies from our department showed that allogeneic bone marrow-derived MSCs are effective and safe for HBV-related ACLF patients (8,9). In our last study, we observed that umbilical cord mesenchymal stem cells (UCMSCs) also showed good therapeutic effects for HBV-related ACLF and liver cirrhosis, and this therapeutic effect could be enhanced by prolonging the UCMSC treatment course, especially for patients with cirrhosis (10). However, a series of factors in uencing the therapeutic effects of MSCs during the treatment of liver failure and cirrhosis have also been proposed by other scholars, such as the type of MSCs, the method of infusion, the dosage of infusion, and the time of infusion (11).…”

“…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).…”

“…The speci c details of the isolation, culture and characterization of UCMSCs were described in a previous report (18). Quality control was performed as described in our previous study (10). Patients received UCMSC transfusions at 1, 2, 3 and 4 weeks after recruitment.…”

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

“…We selected ACLF of type A in this study. The exclusion criteria of the patients were as previously described [ 10 ].…”

“…The results of previous studies from our department showed that allogeneic bone marrow-derived MSCs are effective and safe for HBV-related ACLF patients [ 8 , 9 ]. In our last study, we observed that umbilical cord mesenchymal stem cells (UCMSCs) also showed good therapeutic effects for HBV-related ACLF and liver cirrhosis, and this therapeutic effect could be enhanced by prolonging the UCMSC treatment course, especially for patients with cirrhosis [ 10 ]. However, a series of factors influencing the therapeutic effects of MSCs during the treatment of liver failure and cirrhosis have also been proposed by other scholars, such as the type of MSCs, the method of infusion, the dosage of infusion, and the time of infusion [ 11 ].…”