Emerging pharmacological treatment options for MASLD/MASH

Abstract

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has risen substantially over recent decades, affecting an estimated 38% of the global population. It has become a leading cause of liver disease, with the potential to progress to steatohepatitis (MASH), fibrosis, and ultimately cirrhosis. Management should be multidisciplinary and primarily focused on the treatment of metabolic comorbidities. Historically, pharmacological treatment options for this condition were limited. However, in recent years, based on trials demonstrating improvement in steatohepatitis and regression of fibrosis, novel therapies, including resmetirom and semaglutide, have been approved in patients with MASH and fibrosis (stages F2-F3). Despite these advances, there are still no specific pharmacological treatments available for MASLD in the absence of steatohepatitis or in patients with cirrhosis. Additionally, other agents, including dual or triple incretin receptor agonists, peroxisome proliferator-activated receptor (PPAR) agonists, and fibroblast growth factor 21 (FGF21) analogues, are being evaluated in clinical trials, showing promising results. Over the coming years, new therapeutic strategies, including precise patient stratification, individualized care, combination therapies, treatment switching, and noninvasive treatment response monitoring, are expected to slow disease progression and improve overall prognosis.