Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH)

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of liver disease that poses a global health threat because of its potential to progress to advanced fibrosis, leading to cirrhosis and liver cancer. Recent advances in single-cell methodologies, refined disease models, and genetic and epigenetic insights have provided a nuanced understanding of MASH fibrogenesis, with substantial cellular heterogeneity in MASH livers providing potentially targetable cell-cell interactions and behavior. Unlike fibrogenesis, mechanisms underlying fibrosis regression in MASH are still inadequately understood, although antifibrotic targets have been recently identified. A refined antifibrotic treatment framework could lead to noninvasive assessment and targeted therapies that preserve hepatocellular function and restore the liver's architectural integrity.

Figure 1:

Cellular drivers and potential therapeutics for MASH fibrosis. Potential therapeutics currently undergoing clinical testing to treat MASH are shown in red.

Figure 2:

Molecular regulation of the fibrogenic response. Molecular mechanisms that contribute to MASH fibrosis (left) and MASH fibrosis resolution (right) are depicted.

Figure 3:

Diagnostic and therapeutic opportunities in MASH fibrosis.