Mesenchymal stem cell (MSC) therapy has gained attention as a potential treatment for decompensated liver cirrhosis (DLC), a severe form of liver disease that occurs when the liver can no longer function properly. Liver cirrhosis, especially when caused by chronic hepatitis B (HBV), leads to a significant decline in health, and current treatments do not always yield long-term benefits.
MSCs, particularly those derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC), have shown promise in improving liver function in both animal and human studies. However, the long-term safety and efficacy of MSC therapy, especially in human patients with liver diseases like DLC, remain uncertain. Shi et al.’s study sought to address this gap by observing the effects of UC-MSC therapy in patients with decompensated liver cirrhosis over a follow-up period of 75 months.
Introduction
In recent years, MSC therapy has emerged as a novel approach for treating liver disease, particularly cirrhosis. Research on animal models has demonstrated that bone marrow-derived MSCs (BM-MSCs) can reduce liver fibrosis and even reverse acute liver failure. These findings have also extended to clinical settings where BM-MSC infusions have significantly improved liver function in patients with cirrhosis. Additionally, UC-MSC therapies have been explored, with early studies demonstrating their potential to safely and effectively treat autoimmune-related cirrhosis and improve outcomes in patients with chronic liver failure.
While early studies show promising short-term benefits, there is still limited knowledge about the long-term safety and efficacy of MSC treatments for liver disease. Most studies have only followed patients for up to 12 months. This study aimed to explore the long-term impact of UC-MSC therapy on patients with HBV-related decompensated liver cirrhosis over a period of 75 months, the longest follow-up recorded to date.
Effects of UC-MSC on Long-Term Survival
The primary goal of Shi et al.’s study was to evaluate the long-term survival rates of patients in both groups. Initially, there was no significant difference in survival rates between the UC-MSC group and the control group. However, by using a landmark analysis, the researchers discovered that patients in the UC-MSC group had a significantly higher survival rate during the 13 to 75-month follow-up period, although no notable difference was observed during the first 13 months.
These findings suggest that UC-MSC treatment may take some time to show its full benefits. After the initial 13 months, patients who received UC-MSC therapy experienced improved survival rates compared to those who received only conventional treatment.
Impact of UC-MSC Infusion on Liver Function
To assess the effect of UC-MSC therapy on liver function, the researchers monitored key markers such as albumin (ALB), prothrombin activity (PTA), cholinesterase (CHE), and total bilirubin (TBIL) levels. Results showed that patients in the UC-MSC group experienced significant improvements in ALB and PTA levels compared to the control group during the 48-week follow-up. Additionally, although CHE levels were initially lower and TBIL levels were higher in the UC-MSC group at baseline, these markers improved following the UC-MSC infusions.
The results suggest that UC-MSC therapy helps reduce liver inflammation and enhances liver function over time, improving the liver’s ability to produce essential proteins and process waste products.
Safety and Adverse Effects of UC-MSC Infusion
One of the key concerns in MSC therapy is its long-term safety, particularly the risk of developing hepatocellular carcinoma (HCC) or other complications. In this study, seven patients in the UC-MSC group experienced mild, self-limiting fevers after their infusions, but no other significant short-term side effects were reported.
Over the long term, both groups had similar rates of HCC development, indicating that UC-MSC therapy does not increase the risk of liver cancer compared to standard treatment. Importantly, no other major adverse effects were observed during the 75-month follow-up, suggesting that UC-MSC therapy is a safe option for patients with decompensated liver cirrhosis.
Challenges and Next Steps in UC-MSC Therapy for Liver Cirrhosis”
Despite the positive findings, this study had some limitations. For instance, liver biopsies were not performed due to the high risk for patients with decompensated liver cirrhosis, meaning that histological changes in the liver could not be directly observed. Additionally, the infused UC-MSCs were not tracked within the patients’ bodies due to technical and ethical concerns, leaving some questions about the specific mechanisms of their effect on liver function.
Future research should involve multi-center clinical trials to further explore the use of UC-MSC therapy and confirm the findings of this study. Understanding the precise mechanisms through which UC-MSCs improve survival rates and liver function would also be valuable in optimizing this treatment for liver cirrhosis.
The authors of this study conclude that UC-MSC therapy appears to be a safe and effective treatment option for patients with HBV-related decompensated liver cirrhosis. With improvements in liver function and survival rates becoming evident after 13 months, this treatment holds promise as a novel therapeutic strategy for managing end-stage liver disease.
Source: Shi, M., Li, YY., Xu, RN. et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial. Hepatol Int 15, 1431–1441 (2021). https://doi.org/10.1007/s12072-021-10199-2
St. Petersburg, Florida
