Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition leading to chronic liver disease which generates substantial health care costs. Our aim was to model the impact on disease and economic burden of a hypothetical pharmacologic therapy which halts MASLD fibrosis progression. The U.S. MASLD disease burden model is a Markov model which forecasts disease progression and the impact of diagnosis and treatment. Diagnostic costs for all patients and direct costs for patients with MASLD-related liver disease were also incorporated. MASLD disease burden and economic impacts were modeled for five scenarios: a no treatment case and four interventions incorporating the impact of gradually increasing awareness, screening, and diagnosis, and treatment with anti-steatotic therapy and a future, hypothetical therapy that halts fibrosis progression. Treatment with therapy which only reverses steatosis had minimal (<1 - 2%) effect on cumulative chronic liver disease cases and healthcare costs averted. The scenarios in which a hypothetical therapy halts fibrosis progression resulted in reductions in cases of decompensated cirrhosis (11-39%), hepatocellular carcinoma (10-34%), and liver-related deaths (8-31%), a 9-31% reduction in cumulative DALYs, and $40.5 - $99.1B incremental healthcare costs averted. Increasing diagnosis and treatment for the MASLD population with moderate-to-advanced fibrosis will prevent advanced liver disease and death and will result in reducing the associated direct healthcare costs. Increasing awareness, screening and diagnosis along with introducing pharmacologic therapies that halt fibrosis progression are necessary to realize health and economic benefits for the MASLD population. MASLD, the most rapidly increasing and prevalent liver disease, leads to chronic liver disease which generates substantial health care costs. As disease burden and costs mount, pharmacologic therapy which halts MASLD fibrosis progression is coming to fruition. Modeling the impact on disease progression of a hypothetical pharmacologic therapy which halts MASLD fibrosis progression through multiple scenarios provides insights into the key drivers of the disease and costs associated with it to facilitate best policies and practices to mitigate the burden of MASLD.
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