Abstract
BackgroundUmbilical cord mesenchymal stem cells (UCMSCs) have been demonstrated to have good therapeutic effects in the treatment of HBV-related liver diseases. However, the therapeutic effect of UCMSCs on HBV-related liver failure and liver cirrhosis and the variations in the efficacy of UCMSCs after different treatment courses remain poorly understood. Therefore, this study was designed to answer these two questions.MethodsThis was an observational study that retrospectively considered a 3-year period during which 513 patients who received stem cell infusion and met the criteria of hepatic failure and liver cirrhosis were identified from the databases of the Third Affiliated Hospital of Sun Yat-sen University. The eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the duration of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks of stem cell therapy. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and the patients in group D received less than 4 weeks of stem cell therapy. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and model for end-stage liver disease (MELD) scores were recorded and compared among different groups.ResultsA total of 64 patients met the criteria for liver failure, and 59 patients met the criteria for liver cirrhosis. After UCMSC treatment, the levels of alanine aminotransferase (ALT), glutamic-oxaloacetic transaminase (AST), and total bilirubin (TBIL) at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the prothrombin activity (PTA) and MELD scores gradually improved in only the liver failure group. Four weeks after UCMSC treatment, patients who received prolonged treatment with UCMSCs had a larger decrease in TBIL levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there were no statistically significant differences in the changes in ALT, AST, TBIL, and PTA values and MELD scores between patients with liver failure who received prolonged treatment with UCMSCs and patients with liver cirrhosis who received prolonged treatment with UCMSCs at any time point. However, the median decrease and cumulative decrease in the TBIL level of patients with liver failure with a standard 4-week treatment course were larger than those of patients with liver cirrhosis with a standard 4-week treatment course.ConclusionPeripheral 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.
Highlights
Liver failure and cirrhosis are the results of chronic liver damage caused by many factors, including alcohol, drugs, and hepatitis virus (HBV, HCV, etc.), among which hepatitis B virus (HBV) infection is the most common cause of liver failure and cirrhosis, with high mortality and a large economic burden [1]
A total of 64 patients met the criteria for liver failure, and 59 patients met the criteria for liver cirrhosis
After Umbilical cord mesenchymal stem cells (UCMSCs) treatment, the levels of alanine aminotransferase (ALT), glutamic-oxaloacetic transaminase (AST), and total bilirubin (TBIL) at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores gradually improved in only the liver failure group
Summary
Study population The data of patients with HBV-related liver failure or liver cirrhosis who received UCMSCs at the Third Affiliated Hospital of Sun Yat-sen University between February 2014 and December 2015 were collected. In the liver cirrhosis group, patients who received more than 4 weeks of UCMSC therapy belonged to group C, and group D included patients with liver cirrhosis who were treated with UCMSCs for less than or equal to 4 weeks. All patients in the study received standard clinical treatments (including albumin supplementation, coagulation correction, Sadenosylmethionine infusion, antiviral treatment, and necessary anti-infective treatment) for approximately 1 week before stem cell infusion. UCMSC preparation and transfusion The processing of the umbilical cords and preparation of UCMSCs were performed at the GMP Stem Cell Laboratory Facility of the Biotherapy Center of The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. All analyses were performed as two-sided tests with a 0.05 level of significance
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