Original Abstract

PURPOSE OF REVIEW: Metabolic dysfunction–associated steatotic liver disease (MASLD) represents the hepatic manifestation of ectopic fat accumulation and adipose tissue dysfunction. Excess visceral adiposity promotes adipose tissue hypoxia, macrophage infiltration, and chronic low-grade systemic inflammation, generating systemic metabolic stress that may extend to the lung through a proposed liver–lung axis (hepatopulmonary crosstalk). This systematic review synthesizes current evidence on the associations between MASLD and major respiratory diseases, with emphasis on shared obesity-driven mechanisms. A systematic review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (CRD420261301893). PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched from inception through February 28, 2026. RECENT FINDINGS: Twenty-two studies, 21 observational and 1 Mendelian randomization study (MRS) study reported associations between MASLD and several respiratory conditions, including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), interstitial lung disease, pulmonary hypertension, and respiratory mortality. MASLD prevalence was high among patients with COPD and OSA, and was associated with worse respiratory phenotypes, increased exacerbations, and higher respiratory mortality in several cohorts. Liver fibrosis appeared more strongly associated with impaired lung function and adverse outcomes than steatosis alone. MRS were critically re-evaluated, and do not consistently support causal relationships for most respiratory conditions, with the exception of OSA, which showed evidence suggestive of a potential causal association. Shared mechanisms include visceral adiposity, adipokine imbalance, insulin resistance, systemic cytokine activation (IL-6, TNF-α), endothelial dysfunction, oxidative stress, intermittent hypoxia, and profibrotic transforming growth factor-beta (TGF-β)–mediated pathways. SUMMARY: Current evidence supports a clinically significant association between MASLD and respiratory disease, particularly COPD, OSA and asthma. Recognizing MASLD as a marker of systemic metabolic dysfunction may improve integrated cardiometabolic and pulmonary risk stratification. Prospective and interventional studies targeting weight reduction and metabolic signaling are needed to clarify causality and therapeutic implications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13679-026-00713-8.