Underuse of statins in MASLD despite population-based associations with lower liver stiffness

Background & Aims:

Statins, used for cardiovascular disease (CVD) prevention, may offer hepatoprotective benefits. However, adherence to treatment indications and the associations between statin use, metabolic dysfunction-associated steatotic liver disease (MASLD), and elevated liver stiffness in the general population remain poorly understood.

Methods:

This prospective, population-based study included adults aged ≥40 years between 2011 and 2020. We evaluated statin indications for CVD risk using prevailing European Society of Cardiology/European Atherosclerosis Society clinical practice guidelines based on SCORE2 and SCORE2-Older Persons algorithms. We used multivariable regression to examine associations between statins, MASLD, and elevated liver stiffness, adjusting for demographic, socioeconomic and metabolic covariables. We performed dose-response analyses using WHO defined daily dosages. 

Results: 

Of 6,405 eligible individuals, 6,055 participants were included in the analysis (median age 64 years; 56% female); MASLD was present in 32%, elevated liver stiffness in 4.8%, and statin use in 21%. Participants with MASLD had higher predicted 10-year CVD risk compared to participants without MASLD (p <0.001), yet were less likely to use statins: 33% of individuals with MASLD and an indication for statin treatment remained untreated, compared to 19% of those without MASLD (p <0.001). Statin use was associated with lower prevalence of MASLD (adjusted odds ratio 0.76; 95% CI 0.63–0.92) and elevated liver stiffness (adjusted odds ratio 0.65; 95% CI 0.46–0.92) relative to untreated individuals with a statin treatment indication. The highest statin WHO defined daily dosage category was associated with lower prevalence of MASLD (p = 0.033) and elevated liver stiffness (p = 0.035). 

Conclusions: 

Individuals with MASLD are less likely to use statins despite a contemporary guideline-based indication. Statin use is independently associated with lower prevalence of both MASLD and elevated liver stiffness. These findings underscore the need to improve CVD risk management in this population with the potential added benefit of mitigating MASLD. Impact and implications: In this large prospective, population-based study, statins were underutilized in metabolic dysfunction-associated steatotic liver disease (MASLD) compared to non-MASLD individuals, even though they had the highest cardiovascular risk and met guideline-based treatment criteria. Our findings further demonstrate that individuals who used statins had a lower likelihood of MASLD and elevated liver stiffness compared with statin-eligible individuals who were not treated. Taken together, these results highlight a missed opportunity: optimizing statin use in people with MASLD could strengthen cardiovascular disease prevention while also offering potential benefits for liver health.