Stem cell therapies for liver cirrhosis: a GRADE evaluation through a systematic review

Introduction and Objectives Stem cell therapies have shown potential in treating liver cirrhosis and acute-on-chronic liver failure by promoting liver regeneration. However, their efficacy and safety remain uncertain due to inconsistent results. This systematic review and meta-analysis aimed to evaluate efficacy and safety of stem cell therapies in patients with liver cirrhosis and acute-on-chronic liver failure, compared to standard of care or placebo. Materials and Methods We conducted a systematic review and meta-analysis following PRISMA guidelines. Randomized controlled trials (RCTs) comparing stem cell therapies to standard medical care or placebo for patient important outcomes were included. Risk of bias was assessed using Cochrane RoB 2 tool, and quality of evidence was evaluated with GRADE framework. Results A total of 19 studies were included. Meta-analysis of 15 RCTs (n = 925) provided very low-certainty evidence regarding effects of stem cell therapy on overall mortality. The pooled risk ratio (RR) for mortality was 0.63 (95% CI 0.43 to 0.91; I² = 60%). Ten RCTs (n = 250) assessed effect of stem cell therapy on Model for End-Stage Liver Disease (MELD) scores. The pooled mean difference (MD) was -1.22 (95% CI -2.25 to -0.19; I² = 51%). The certainty in evidence was rated down for risk of bias and imprecision for most outcomes. Conclusions This systematic review and meta-analysis provides very low-certainty evidence regarding efficacy of stem cell therapies for liver cirrhosis and acute-on-chronic liver failure. Further high-quality research is necessary to clarify role of stem cells in treating liver diseases and to ensure safety and efficacy.