Booklets

Metabolic dysfunction-associated fatty liver disease (MAFLD)1, formerly known as non-alcoholic fatty liver disease (NAFLD), is an umbrella term covering the spectrum of fatty liver diseases, ranging from isolated steatosis to the most severe form, metabolic dysfunction-associated steatohepatitis (MASH)1, formerly known as non-alcoholic steatohepatitis (NASH). Over the last three decades, the prevalence of MAFLD has surged by over 50%, paralleling the rising pandemics of obesity, pre-diabetes, and type 2 diabetes, affecting more than 30% of the global general population2. The increasing prevalence of MASH has resulted in it becoming the leading cause of liver transplantation in the USA and Europe3.

Diagnosis and management of MASH present multiple challenges. Symptoms are often silent or non-specific, leading to delayed diagnosis. There is, therefore, an urgent need for approved and clinically applicable biomarkers for MASH to facilitate early detection. Another significant gap is the lack of specific treatments for MAFLD and MASH, despite their high incidence and growing global health impact.

In this context, the advent of novel therapeutic avenues is particularly promising. The introduction of thyroid receptor beta agonists, such as Resmetirom, marks a significant advance in
the management of MASH. Resmetirom has recently become
the first drug in its class approved by the FDA4, representing a meaningful step towards addressing the underlying metabolic dysfunction associated with MASH. By targeting thyroid hormone signaling pathways, resmetirom has shown potential in reducing hepatic fat, fibrosis, and improving related metabolic parameters.

Alongside thyroid receptor beta agonists, the PPAR (peroxisome proliferator-activated receptor) class is under investigation as a potential therapeutic avenue for treating MAFLD and MASH. PPARα and PPARγ agonists are particularly being explored for their roles in modulating lipid metabolism and insulin sensitivity, which are key factors in the management of fatty liver diseases.

This latest booklet and slide deck from the Residual Risk Reduction Initiative provides an accessible resource on MASH epidemiology, diagnosis, and management.