Background & Aims: Social determinants of health (SDOH) impact disease risk and severity leading to health disparities and impeding health equity. Though important in mitigating adverse health outcomes, SDOH impacting metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence and severity are understudied and results are conflicting. The aim of this systematic review and meta-analysis was to assess the impact of specific SDOH factors on MASLD disease burden for adults in the United States (US). Methods: We searched MEDLINE, Embase and Cochrane databases per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies from January 2010- May 2024 were included. Quantitative studies of adults in the US that evaluated SDOH beyond race/ethnicity were included. Outcomes included prevalence of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), MASH-associated advanced fibrosis or cirrhosis and clinical outcomes. Results: We identified 18 studies comprising of 547,634 total subjects from 11 unique cohorts. Nine studies evaluated MASLD prevalence, three MASH prevalence, eight MASH-associated advanced fibrosis/cirrhosis prevalence, and nine clinical outcomes. High diet quality was the most consistent SDOH factor associated with both MASLD and MASH-associated advanced fibrosis/cirrhosis prevalence (summarized OR of 0.76 p <0.01, and 0.74 p <0.01, respectively). Lower income was most consistently associated with risk of clinical outcomes (significant in 3/9 studies). Conclusions: Diet quality was the most consistent SDOH associated with disease prevalence and severity in MASLD, with the remainder of SDOH showing inconsistent associations. Prospective assessments using consistent, validated tools to assess the impact of specific SDOH on MASLD disease burden are needed to inform public health interventions to mitigate health disparities in MASLD.

RL serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals and Viking Therapeutics. In addition his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Co-founder of LipoNexus Inc.

RL receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), and NIAAA (U01AA029019). MT is supported by the SDSU-UCSD Cancer Research and Education to Advance Health Equity Partnership.

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Source data are openly available in published studies.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Study materials and data are available in published articles for this meta-analysis.