AI Article Synopsis
- Statin use shows potential benefits for patients with non-alcoholic fatty liver disease (NAFLD), but previous evidence has been inconsistent; this study aimed to comprehensively examine the effects and mechanisms of statins on NAFLD.
- In two cohorts—a general population and a group with biopsy-proven NAFLD—statin use was linked to lower rates of NASH and fibrosis, and a meta-analysis supported these findings; though associations for NAFLD were less significant.
- The study also demonstrated that statins reduced lipid accumulation in liver cells and decreased inflammation in macrophages, suggesting that their protective effects in liver disease may arise from these mechanisms.
Article Abstract
Background: Statin use could benefit patients with non-alcoholic fatty liver disease (NAFLD), but the evidence is segmented and inconclusive. This multidimensional study comprehensively investigated the potential benefits and mechanism-of-action of statins in NAFLD.
Methods: A cross-sectional investigation was performed within the Rotterdam Study (general population; n = 4.576) and the PERSONS cohort (biopsy-proven NAFLD patients; n = 569). Exclusion criteria were secondary causes for steatosis and insufficient data on alcohol, dyslipidemia or statin use. Associations of statin use with NAFLD (among entire general population), fibrosis and NASH (among NAFLD individuals and patients) were quantified. These results were pooled with available literature in meta-analysis. Last, we assessed statins' anti-lipid and anti-inflammatory effects in 3D cultured human liver organoids and THP-1 macrophages, respectively.
Findings: Statin use was inversely associated with NAFLD in the Rotterdam study compared to participants with untreated dyslipidemia. In the PERSONS cohort, statin use was inversely associated with NASH, but not with fibrosis. The meta-analysis included 7 studies and indicated a not significant inverse association for statin use with NAFLD (pooled-Odds Ratio: 0.69, 95% Confidence Interval: 0.46-1.01) and significant inverse associations with NASH (pooled-OR: 0.59, 95% CI: 0.44-0.79) and fibrosis (pooled-OR: 0.48, 95% CI: 0.33-0.70). In vitro, statins significantly reduced lipid droplet accumulation in human liver organoids and downregulated expression of pro-inflammatory cytokines in macrophages.
Interpretation: Pooled results demonstrated that statin use was associated with a lower prevalence of NASH and fibrosis and might prevent NAFLD. This may be partially attributed to the anti-lipid and anti-inflammatory characteristics of statins. Given their under-prescription, adequate prescription of statins may limit the disease burden of NAFLD.
Funding: ZonMw, KWF, NWO, SLO, DGXII, RIDE, National and regional government, Erasmus MC and Erasmus University.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758527 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2022.104392 | DOI Listing |
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