Circadian and behavioral timing in MASLD: a systematic review of human observational studies

Abstract

Summary Background Circadian disruption may affect metabolism through altered timing of sleep, activity, light exposure, hormonal rhythms, and food intake. However, its relationship with metabolic dysfunction-associated steatotic liver disease (MASLD), including fibrosis and cirrhosis remains unclear. To evaluate associations between circadian and behavioural timing exposures and MASLD in observational studies. Methods PubMed, Embase, and Scopus were searched from inception to 14 July 2026. Eligible studies examined naturally occurring timing-related exposures in adults and reported steatosis, fibrosis, cirrhosis, or quantitative liver-fat outcomes. Findings were synthesized narratively because heterogeneity precluded pooling. Risk of bias was assessed using AXIS or the Newcastle–Ottawa Scale, and certainty using an adapted domain-level GRADE approach (PROSPERO Registration number: CRD420261381636). Findings Twenty-four independent MASLD-related evidence sources were included in the primary synthesis; two additional mixed-aetiology cirrhosis studies were considered contextually. Shift work showed the most consistent associations and most longitudinal evidence. Chronotype was generally associated with disease occurrence but inconsistently with advanced outcomes: intermediate or late chronotype was associated with fibrosis in one clinical cohort, whereas morning chronotype was not independently associated with incident cirrhosis in a prospective cohort. Later sleep timing was associated with prevalent MASLD and, in one NHANES analysis, fibrosis. Evidence for objective rest-activity rhythms, light exposure, meal timing, and melatonin phase remained limited or heterogeneous. Mixed-aetiology cirrhosis studies suggested that advanced liver disease may itself disrupt circadian physiology. Interpretation Circadian and behavioural timing exposures showed trends associated with MASLD-related outcomes, with the most consistent evidence for shift work. Residual confounding, cross-sectional designs, self-reported exposures, heterogeneous outcomes, and reverse causality preclude causal conclusions. Prospective studies using objective circadian phenotyping and standardized fibrosis outcomes are needed. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.