Metabolic Dysfunction-Associated Steatotic Liver Disease

Targher, Giovanni M.D.
Valenti, Luca M.D.
Byrne, Christopher D. M.B., Ch.B.

¹Department of Medicine, University of Verona, Verona, Italy
²Metabolic Diseases Research Unit, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy
³Department of Pathophysiology and Transplantation, University of Milan, Milan
⁴Department of Precision Medicine, Biological Resource Center Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan
⁵National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom
⁶National Institute for Health and Care Research, Southampton Biomedical Research Centre, University of Southampton, Southampton, United Kingdom

Prof. Targher can be contacted at [email protected] or at the Metabolic Diseases Research Unit, IRCCS Sacro Cuore Don Calabria Hospital, Viale Luigi Rizzardi, 4, 37024 Negrar di Valpolicella, Italy

Profs. Targher, Valenti, and Byrne contributed equally to this article.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 393(7):p 683-698, August 14, 2025. | DOI: 10.1056/NEJMra2412865

Key Points

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

MASLD is a multisystem disease that has become a public-health problem worldwide.
Metabolic dysfunction is key to the pathogenesis and consequences of MASLD.
The clinical burden of MASLD consists mainly of liver-related disease and death and high rates of fatal and nonfatal cardiovascular disease, chronic kidney disease, type 2 diabetes, and certain extrahepatic cancers, especially extrahepatic gastrointestinal cancers.
There is a pressing need for drugs to treat MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH).
In March 2024, resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, was the first drug conditionally approved by the Food and Drug Administration for treating adults with noncirrhotic MASH and moderate-to-advanced fibrosis.
Incretin-based drugs (especially semaglutide at a dose of 2.4 mg per week) and other metabolism-based pharmacotherapies are showing promise as therapeutic options not only for steatotic liver disease but also for cardiovascular-kidney-metabolic complications that are strongly related to MASLD.

Metabolic Dysfunction-Associated Steatotic Liver Disease

MASLD has become the most common chronic liver disease worldwide. The authors review the features of the disease as well as pharmacotherapies targeting the associated liver and cardiovascular-renal-metabolic issues.