Highlight
Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent among older adults and commonly coexists with multimorbidity, leading to polypharmacy, especially in those aged 75 and older. This study reveals that polypharmacy in MASLD patients reflects high cardiometabolic burden but also poses risks that require vigilant medication review and individualized care plans.
Study Background
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), represents a spectrum of liver conditions linked to metabolic abnormalities such as insulin resistance, obesity, and dyslipidemia. MASLD frequently affects older adults with coexisting cardiometabolic diseases including diabetes and hypertension. This multimorbidity poses challenges for clinical management due to the necessity for multiple medications, heightening the risk of polypharmacy-related adverse effects in geriatric patients.
Polypharmacy—commonly defined as the use of five or more medications—is associated with increased risks of drug interactions, adverse drug events, cognitive impairment, and decreased functional status. In populations with MASLD, these risks are amplified because cardiometabolic comorbidities require aggressive pharmacologic management to prevent disease progression and cardiovascular mortality. Prior to this study, the burden of polypharmacy in older adults with MASLD was not well characterized, highlighting an important clinical knowledge gap.
Study Design
The investigation was a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycles. It included adults aged 65 years or older with available transient elastography data to assess steatosis and fibrosis. MASLD was defined by the presence of liver steatosis alongside at least one metabolic risk factor (e.g., obesity, diabetes, hypertension).
Polypharmacy was operationalized as the use of five or more medications. Participants were stratified by age groups: 65-69 years, 70-74 years, and 75 years and older. Survey-weighted analyses accounted for complex sampling design, and multivariable logistic regression models adjusted for comorbidities to evaluate associations between age, MASLD presence, and polypharmacy prevalence.
Key Findings
The study estimated that among approximately 42 million US adults aged 65 and older, 39.8% had MASLD. Across age groups, MASLD individuals had significantly higher prevalence of diabetes, obesity, and greater cardiometabolic comorbidity burden compared to those without MASLD (all p<0.01). Notably, the proportion of women with MASLD declined with advancing age (from 55.5% in 65-69 years to 39.3% in ≥75 years, p=0.04).
Polypharmacy was substantially more common among older adults with MASLD, particularly in those aged 75 years and above, where 60.3% experienced polypharmacy. This rate was significantly higher than younger MASLD counterparts (36.9%, p=0.002) and non-MASLD peers in the same age group (42.7%, p=0.005). After adjusting for comorbidities, MASLD adults aged ≥75 had more than three times the odds of polypharmacy compared to those aged 65-69 (adjusted odds ratio [aOR] 3.12; 95% confidence interval [CI] 2.21-4.42).
Medication class analysis revealed that MASLD adults had higher use of antidiabetic drugs but lower use of antihypertensive agents relative to those without MASLD (p<0.05). This suggests targeted pharmacotherapy that corresponds to the metabolic disease profile typical in MASLD, although the relative lower antihypertensive use warrants further investigation.
Expert Commentary
This study emphasizes the clinical complexity of managing older adults with MASLD, where the interplay of multiple cardiometabolic conditions necessitates comprehensive medication regimens. The markedly elevated polypharmacy rates in those ≥75 years underscore the need for vigilant medication reconciliation to balance therapeutic benefits against the risk of adverse drug reactions, especially given the vulnerability of older patients to geriatric syndromes, including falls, cognitive decline, and frailty.
The finding that antihypertensive use was lower in MASLD patients is intriguing and may reflect under-treatment or differences in disease phenotypes. Considering guidelines advocate for aggressive management of cardiometabolic risk factors to retard liver disease progression and reduce cardiovascular events, this observation warrants further clinical scrutiny.
Limitations include the retrospective study design and reliance on cross-sectional NHANES data limiting causal inferences. Additionally, medication adherence, dosing, and appropriateness were not assessed, which are critical components when evaluating polypharmacy impacts.
Conclusion
Polypharmacy affects a significant proportion of older adults with MASLD, particularly those aged 75 and above, reflecting their higher multimorbidity burden. While aggressive management of cardiometabolic comorbidities is essential to mitigate MASLD progression and reduce mortality risks, clinicians must carefully balance these interventions against potential polypharmacy-related harms.
Incorporating age-appropriate medication review interventions, deprescribing protocols where feasible, and patient-centered goals of care discussions are pivotal strategies to optimize outcomes in this high-risk population. Future research should focus on longitudinal outcomes of polypharmacy in MASLD and develop tailored clinical guidelines to guide medication management in older adults with this increasingly prevalent liver condition.
Funding and ClinicalTrials.gov
The study was presumably supported by institutional funding linked to the NHANES dataset; however, detailed funding disclosures were not provided. The study is observational and does not appear to be registered on ClinicalTrials.gov.
References
1. Younossi ZM, Henry L. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Clin Liver Dis. 2016;20(2):263-274. doi:10.1016/j.cld.2015.11.006
2. Maher JJ, et al. Multimorbidity and Polypharmacy in Nonalcoholic Fatty Liver Disease: Implications for Management. Clin Gastroenterol Hepatol. 2021;19(11):2271-2279.
3. American Geriatrics Society 2019 Updated Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694.
4. Wang M, Usman L, Cho B, Covinsky K, Lai JC. Polypharmacy Among Older Adults with Metabolic Dysfunction-Associated Steatotic Liver Disease. J Gen Intern Med. 2026 Jul 14. doi: 10.1007/s11606-026-07445-4.