Huang Daniel Q, Wong Vincent W S, Rinella Mary E, Boursier Jerome, Lazarus Jeffrey V, Yki-Järvinen Hannele, Loomba Rohit
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
Nat Rev Dis Primers. 2025 Mar 6;11(1):14. doi: 10.1038/s41572-025-00599-1.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors. The obesity epidemic and the growing prevalence of type 2 diabetes mellitus greatly contribute to the increasing burden of MASLD. The treatment and prevention of major metabolic comorbidities such as type 2 diabetes mellitus and obesity will probably slow the growth of MASLD. In 2023, the field decided on a new nomenclature and agreed on a set of research and action priorities, and in 2024, the US FDA approved the first drug, resmetirom, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis. Reliable, validated biomarkers that can replace histology for patient selection and primary end points in MASH trials will greatly accelerate the drug development process. Additionally, noninvasive tests that can reliably determine treatment response or predict response to therapy are warranted. Sustained efforts are required to combat the burden of MASLD by tackling metabolic risk factors, improving risk stratification and linkage to care, and increasing access to therapeutic agents and non-pharmaceutical interventions.
代谢功能障碍相关脂肪性肝病（MASLD）是一个统称，涵盖了从代谢功能障碍相关脂肪性肝病（即单纯性肝脂肪变性）到代谢功能障碍相关脂肪性肝炎（一种可进展为纤维化、肝硬化和肝细胞癌的进行性坏死性炎症性疾病）。据估计，全球超过三分之一的成年人受MASLD影响。MASLD与胰岛素抵抗、肥胖、肠道微生物群失调和遗传风险因素密切相关。肥胖流行和2型糖尿病患病率的不断上升极大地加重了MASLD的负担。治疗和预防2型糖尿病和肥胖等主要代谢合并症可能会减缓MASLD的增长。2023年，该领域确定了新的命名法，并就一系列研究和行动重点达成一致，2024年，美国食品药品监督管理局（FDA）批准了首款药物resmetirom，用于治疗伴有中度至重度纤维化的非肝硬化代谢功能障碍相关脂肪性肝炎。能够替代组织学用于MASLD试验中患者选择和主要终点的可靠、经过验证的生物标志物将极大地加速药物研发进程。此外，还需要可靠地确定治疗反应或预测治疗反应的非侵入性检测方法。需要持续努力，通过应对代谢风险因素、改善风险分层以及与医疗保健的联系，以及增加获得治疗药物和非药物干预措施的机会，来应对MASLD的负担。
