Journal Article

Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis

Ramasamy, Adaikalavan, Devasia, Arun George, Leo, Chen Huei

2025

Overview

In recent years, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been proposed to better connect liver disease to metabolic dysfunction, which is the most common chronic liver disease worldwide. MASLD affects more than 30% of individuals globally, and it is diagnosed by the combination of hepatic steatosis and obesity, type 2 diabetes, or two metabolic risk factors. MASLD begins with the buildup of extra fat, often greater than 5%, within the liver, causing liver hepatocytes to become stressed. This can proceed to a more severe form, metabolic dysfunction-associated steatohepatitis (MASH), in 20–30% of people, where inflammation in the liver causes tissue fibrosis, which limits blood flow over time. As fibrosis worsens, MASH may lead to cirrhosis, liver failure, or even liver cancer. While the pathophysiology of MASLD is not fully known, the current “multiple-hits” concept proposes that dietary and lifestyle factors, metabolic factors, and genetic or epigenetic factors contribute to elevated oxidative stress and inflammation, causing liver fibrosis. This review article provides an overview of the pathogenesis of MASLD and evaluates existing therapies as well as pharmacological drugs that are currently being studied in clinical trials for MASLD or MASH.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Cancer / Carbohydrates / Cell death / Cytokines / Development and progression / Diabetes / Diet / Enzymes / Epigenetic inheritance / Fatty acids / Fatty liver / Fatty Liver - drug therapy / Fatty Liver - etiology / Fatty Liver - metabolism / Fatty Liver - pathology / Fatty Liver - therapy / Health aspects / Humans / Hypotheses / Inflammation / Insulin resistance / Lifestyles / Liver / Liver - metabolism / Liver - pathology / Liver cancer / Liver cirrhosis / Liver Cirrhosis - metabolism / Liver Cirrhosis - pathology / Liver diseases / Liver failure / Medical research / Medicine, Experimental / Metabolic Diseases - complications / Metabolic Diseases - metabolism / Metabolic syndrome / Microbiota / Non-alcoholic Fatty Liver Disease - metabolism / Obesity / Obesity - complications / Oils & fats / Oxidative Stress / Pathogenesis / Pathophysiology / Processed foods / Proteins / Review / Risk factors / Tumor necrosis factor-TNF / Type 2 diabetes