The Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the US: A Total System Value Evidence Framework
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We present a qualitative evidence framework used to visualise the complex interconnectivity between MASLD/MASH, its outcomes, and the effects on the broader system.
Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), where lipids accumulate in the liver, may progress to metabolic dysfunction-associated steatohepatitis (MASH), a disease stage characterised by liver inflammation and progressive damage. We aimed to develop an evidence framework to characterise the burden of MASLD/MASH from a total system perspective in the US, encompassing clinical, societal and economic consequences.
Ovid/PubMed searches were conducted to identify evidence across the MASLD/MASH spectrum, including epidemiology, pathophysiology, cardiometabolic comorbidities, outcomes (clinical, societal and economic) and healthcare resource use. Evidence was categorised and connected to visually represent how MASLD/MASH impacts the wider system. A qualitative assessment of the strength of the evidence was conducted to identify uncertainty and evidence gaps. The framework was validated by clinical experts.
In our novel framework, disease prevalence, staging and progression, risk factors, hepatic and non-hepatic outcomes, were connected to form a system. Clinical features were linked to outcomes to enable value-mapping and the illustration of disease burden from multiple perspectives. The quality of evidence was heterogenous, ranging from meta-analyses to single, small studies. Underdiagnosis of MASH creates uncertainty in terms of total prevalence, disease stage prevalence and burden. High-quality evidence related to risk of some clinical outcomes, but limited evidence was available to correlate progression with other outcomes.
The MASLD/MASH qualitative evidence framework is a useful tool to visualise the complex connections between disease features and outcomes, identify value drivers, support economic modelling and to inform evidence generation needs.
Recommended citation: Ota, R., Bedwell, A., Tefos, F., Weitzel, T., Padgett, T., Fidler, C. (2025) The Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the US: A Total System Value Evidence Framework. ISPOR EU 2025, 10 November 2025; Presentation.