Presentation (CTI)

OBJECTIVES: 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 MASLD/MASH from a total system perspective in the US, encompassing clinical, societal and economic consequences.
METHODS: 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.
RESULTS: In our novel framework, disease prevalence, staging and progression (measured invasively [biopsy-determined ‘F-stage’] and non-invasively [e.g. FIB-4 scoring]), risk factors (e.g., metabolic syndrome, age, sex), hepatic (hepatocellular carcinoma, liver transplant, cardiovascular events) 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 the perspectives of multiple stakeholders: patients (quality of life, mortality), society (indirect costs, including informal care, absenteeism/presenteeism), healthcare providers (direct costs, resource use), and the environment. 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 (e.g., transplant, complications), but limited evidence was available to correlate progression with other outcomes (e.g., quality of life, productivity).
CONCLUSIONS: A qualitative framework of disease elements and outcomes can be constructed, notwithstanding data limitations. 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.