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The MAESTRO-NASH phase 3 trial evaluated resmetirom in adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with significant liver fibrosis. At 52 weeks, resmetirom produced higher rates of both MASH resolution without worsening of fibrosis and improvement in fibrosis without worsening of MASH compared with placebo. The trial is important because it demonstrates a path toward disease-modifying pharmacotherapy in a condition historically managed largely through lifestyle intervention and treatment of metabolic risk factors. For internists, MASLD/MASH is increasingly relevant because obesity, type 2 diabetes and cardiovascular disease frequently coexist with liver disease. Risk assessment should therefore move beyond liver enzymes alone and incorporate fibrosis estimation and appropriate referral pathways. Resmetirom is not appropriate for every patient with fatty liver, and the trial population had selected fibrosis stages. Nonetheless, the results reinforce the idea that MASH can be an active therapeutic target rather than simply an incidental imaging finding. Multidisciplinary management remains essential, with attention to weight, glycemia, lipids, blood pressure, alcohol exposure and cardiovascular risk.
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The MAESTRO-NASH phase 3 trial evaluated resmetirom in adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with significant liver fibrosis. At 52 weeks, resmetirom produced higher rates of both MASH resolution without worsening of fibrosis and improvement in fibrosis without worsening of MASH compared with placebo. The trial is important because it demonstrates a path toward disease-modifying pharmacotherapy in a condition historically managed largely through lifestyle intervention and treatment of metabolic risk factors. For internists, MASLD/MASH is increasingly relevant because obesity, type 2 diabetes and cardiovascular disease frequently coexist with liver disease. Risk assessment should therefore move beyond liver enzymes alone and incorporate fibrosis estimation and appropriate referral pathways. Resmetirom is not appropriate for every patient with fatty liver, and the trial population had selected fibrosis stages. Nonetheless, the results reinforce the idea that MASH can be an active therapeutic target rather than simply an incidental imaging finding. Multidisciplinary management remains essential, with attention to weight, glycemia, lipids, blood pressure, alcohol exposure and cardiovascular risk.
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