代谢功能障碍相关脂肪性肝病最具潜力的新型药物选择OA

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become one of the most common chronic liver diseases worldwide.Its progressive phenotype,metabolic dysfunction-associated steatohepatitis(MASH),can further progress to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,and is closely associated with obesity,type 2 diabetes mellitus,chronic kidney diseases,and cardiovascular diseases.Lifestyle intervention remains the cornerstone of MASLD management.However,for patients with active hepatitis and moderate-to-severe fibrosis,pharmacotherapy has become an important complement to alter the disease course.In recent years,the selective thyroid hormone receptor-β agonist resmetirom and the glucagon-like peptide-1 receptor agonist semaglutide have been approved by the U.S.Food and Drug Administration(FDA)for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis in adults,marking the entry of MASH pharmacotherapy into the stage of evidence-based treatment.Meanwhile,dual or multi-incretin agonists,peroxisome proliferator-activated receptor agonists,fibroblast growth factor 21 analogues,inhibitors of hepatic de novo lipogenesis,and genetically targeted therapies are also showing important promise.Future pharmacotherapy for MASLD should focus not only on promoting MASH resolution and fibrosis improvement,but also on achieving hepatic benefits and integrated control of cardiovascular-renal-hepatic-metabolic risks.For the stage of MASH cirrhosis,its specific pathological mechanisms,effective endpoint setting and generalizable therapeutic strategies still require further breakthroughs.