From liver to limb: Exploring the association between fatty liver disease and peripheral artery disease-A systematic review

Abstract

Introduction: Fatty liver disease, encompassing nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and the recently redefined metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing global health concern with significant cardiovascular implications. Peripheral artery disease (PAD), a common manifestation of systemic atherosclerosis, shares key pathophysiological mechanisms with fatty liver disease, including insulin resistance, systemic inflammation and endothelial dysfunction. Although emerging evidence suggests a link between fatty liver disease and PAD, the nature and extent of this association remain unclear. This systematic review synthesizes current research evaluating the relationship between fatty liver disease and PAD.

Methods: A systematic search of PubMed, Embase and Scopus was conducted up to December 19, 2024, following PRISMA 2020 guidelines. Eligible observational studies assessing PAD in MASLD, MAFLD or NAFLD patients were included. Quality assessment was performed independently by two reviewers using the Newcastle-Ottawa Scale (NOS).

Results: Eleven observational studies, including approximately 848,027 participants, were analysed. Most studies reported a significant association between NAFLD or MAFLD and increased PAD risk, particularly in individuals with type 2 diabetes and metabolic syndrome. Studies using MAFLD criteria demonstrated a stronger association with PAD than those using NAFLD definitions. The presence of hepatic fibrosis was linked to a higher PAD risk in some studies. However, not all studies found a consistent relationship, and a few reported no independent association between fatty liver disease and PAD, highlighting the need for further research. Notably, none of the included studies used MASLD criteria.

Conclusions: Patients with NAFLD or MAFLD, particularly those with metabolic comorbidities, may have an elevated risk of PAD. The severity of liver disease, including fibrosis, appears to contribute to this risk. Future studies should incorporate MASLD definitions and advanced diagnostic methods to clarify this relationship and guide clinical strategies for integrated cardiovascular and liver disease management.

Keywords: cardiovascular risk; fatty liver; liver fibrosis; metabolic dysfunction‐associated steatotic liver disease (MASLD); metabolic syndrome; peripheral artery disease (PAD); systemic inflammation.