Targeting Metabolism: Innovative Therapies for MASLD Unveiled

Abstract

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.

Keywords: MASLD; inflammatory response; lipidosis; metabolic syndrome; targeted therapy.

Figure 1

Pathophysiological changes of MASLD. The continuum of disease progression in MASLD encompasses the transition from a normal liver to steatosis, then to MASH, followed by fibrosis and cirrhosis, ultimately culminating in MASH-related HCC. The progression of disease in MASLD is characterized by a transition from normal liver to steatosis, followed by MASH, fibrosis, cirrhosis, and ultimately MASH-related HCC. Nonetheless, as previously indicated, this does not represent a singular linear progression relationship.

Figure 2

A summary of MASLD-associated targets and their respective targeted therapies. Topics covered include steatosis, MASH, fibrosis, cirrhosis, MASH-related HCC, and the influence of gut microbiota and miRNAs on metabolism and disease progression.