Beyond their established role in reducing cardiovascular mortality through lipid-lowering, statins exert pleiotropic effects that may confer clinical benefit in cirrhosis, including anti-oxidative, anti-inflammatory, anti-proliferative, and anti-fibrotic properties, as well as improvements in hepatic endothelial function 1. This systematic review and meta-analysis 2 included 25 studies published before July 2025 comparing cirrhotic patients treated with statin therapy with those not treated with statin therapy. In total, 81,992 patients from nine randomised controlled trials (RCTs) and 16 observational studies were included. Statins were associated with significantly lower all-cause mortality in the overall pooled analysis (unadjusted odds ratio OR 0.59; 95% CI 0.48–0.71), and this finding was consistent across both RCTs and observational studies. The effect of statins on hepatic decompensation was also examined, but with inconsistent findings across study designs. In the overall analysis, statin therapy was associated with lower odds of decompensation (unadjusted OR 0.56; 95% CI: 0.47–0.66), specifically ascites and variceal haemorrhage. However, this finding was driven by observational data, as statins were not found to reduce hepatic decompensation in RCTs alone (OR 0.75; 95% CI: 0.52–1.09). In an analysis of RCTs, statins were associated with a reduction in hepatic venous pressure gradient (HVPG; mean difference −1.14 mmHg). Observational data indicated lower odds of hepatocellular carcinoma amongst statin users (adjusted HR 0.61; 95% CI: 0.46–0.82); however, no RCT reported this outcome. This meta-analysis demonstrates an association between statin use and reduction in all-cause mortality in persons with cirrhosis, though some limitations warrant consideration. This data are primarily from retrospective cohort studies with only 813 of 81,992 included patients from RCTs. While observational studies provide real-world insight, they cannot establish causality and remain susceptible to residual confounding. Statin users may differ systematically in ways unaccounted for in the analysis or receive more guideline-based care, making it difficult to isolate the independent effect of statins. Notably, there was significant heterogeneity across studies, including statin choice, dose and duration in addition to cirrhosis stage and aetiology, co-interventions (e.g., non-selective beta blocker, NSBB), and duration of follow-up. Cause-specific mortality was not examined, raising the possibility that the observed mortality benefit may not reflect liver-related mechanisms. Notably, statin therapy was associated with only modest reductions in HVPG (mean difference −1.14 mmHg), which is unlikely to fully account for the mortality benefit observed. In contrast, studies of NSBBs have defined clinically significant HVPG response as a reduction of at least 20% or to below 12 mmHg 3. Moreover, hepatic decompensation was not consistently lower in statin-treated patients when RCTs were examined, an outcome that would be expected with a clinically meaningful reduction in portal pressure, but this may have been limited by shorter follow-up duration in RCTs as compared to observational studies 4. Overall, this meta-analysis suggests a mortality and chemopreventive benefit of statins in cirrhosis. However, current data are insufficient to justify routine use of statins as liver-directed disease-modifying therapy, emphasising the need for more RCTs to define their optimal role in cirrhosis. Emily Stephenson: writing – original draft, writing – review and editing. Suzanne Sharpton: writing – review and editing, conceptualization, supervision. The authors have nothing to report. Suzanne Sharpton serves on an advisory board for Takeda Pharmaceuticals, and her institution has received research funding from Takeda, AstraZeneca, and Boehringer Ingelheim. This article is linked to de Faria Moraes et al. paper. To view this article, visit https://doi.org/10.1111/apt.70526. The authors have nothing to report.
Stephenson et al. (Tue,) studied this question.