Pharmacotherapy for MASH: Heart-Liver Co-Management

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30% of adults, with about 30% of cases progressing to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to cirrhosis and hepatocellular carcinoma. Cardiovascular disease (CVD) is the leading cause of death among affected patients, highlighting the need for integrated heart-liver co-management. MASLD and CVD share common pathophysiological mechanisms, including insulin resistance, low-grade inflammation, atherogenic dyslipidemia, and oxidative stress, creating a bidirectional interplay that drives disease progression. Effective management of MASLD requires addressing not only hepatic steatosis, inflammation, and fibrosis but also managing cardiovascular risk. Current clinical practice and trials face several challenges, including the underdiagnosis of MASLD, limited collaboration between hepatologists and cardiologists, and a paucity of pharmacological options that safely target both the liver and heart. This review covers three main pharmacological approaches: metabolic-targeted therapies, which improve the upstream metabolic milieu; liver-targeted therapies, which focus on MASH and fibrosis but require further evaluation for cardiovascular safety; and cardiovascular therapies, which may provide hepatoprotective effects but need further study. The review discusses the benefits and limitations of these pharmacotherapies, emphasizing the importance of an integrated heart-liver co-management approach to improve clinical outcomes for patients living with MASLD.

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ORCID for Chris Byrne: orcid.org/0000-0001-6322-7753

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