Transplantation of Autologous Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Decompensated Liver Cirrhosis: A Real-World Evidence Study in a Population-Based Cohort.

Background/aims: Despite medical advances in recent decades, the mortality rate of advanced liver cirrhosis remains high. Although liver transplantation remains the most effective treatment, candidate selection is limited by donor availability and alcohol abstinence requirements. Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has shown promise for the treatment of advanced cirrhosis. However, trials tend to involve small patient samples, and long-term follow-up studies are lacking. In this study, BM-MSC transplantation outcomes were assessed using real-world evidence (RWE) along with dynamic matching to reduce bias.

Methods: A control group was selected using exposure density sampling to reduce immortal time bias. Mortality rates were compared using Kaplan-Meier survival analysis and Cox proportional-hazard regression models, with adjustments for baseline characteristics.

Results: The cumulative incidences of 5-year mortality were 0%, 5.0%, and 11.3% at 1, 3, and 5 years in the BM-MSC group, compared with 7.0%, 10.9%, and 42.1% in the control group, respectively. Kaplan-Meier analysis revealed no significant difference in 1-year mortality between the BM-MSC and control groups (p=0.140). However, 3- and 5-year mortalities were significantly lower in the BM-MSC group (p<0.001). The adjusted hazard ratios for 5-year mortality in the BM-MSC group were 0.18 (95% confidence interval [CI], 0.04 to 0.87) and 0.14 (95% CI, 0.02 to 0.82) under the two models, indicating a lower mortality risk than in controls.

Conclusions: This study highlights the potential of BM-MSC transplantation in reducing long-term mortality in patients with alcoholic cirrhosis. The use of RWE provides a valuable framework for evaluating treatment efficacy and overcoming randomized controlled trial limitations, setting a precedent for future clinical research.