Pirola Luciano
Carmen Laboratory, INSERM Unit 1060-Lyon 1 University, Pierre Benite 69310, France.
World J Gastroenterol. 2025 Jan 28;31(4):99312. doi: 10.3748/wjg.v31.i4.99312.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions. Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today, resmetirom, a thyroid hormone receptor b agonist, is the only approved agent. The dual PPAR α and δ agonist elafibranor has also undergone extensive clinical testing, which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD. As alcohol-associated liver disease and MASLD can be interconnected, whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating. Writing recently in the , Koizumi reported using a mouse model of alcohol-associated liver disease and found that hepatic steatosis, liver fibrosis, and hepatocyte apoptosis were alleviated by administration of elafibranor. Although preclinical in nature, these data support the potential beneficial action of elafibranor in alcohol-induced MASLD, warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.
代谢功能障碍相关脂肪性肝病（MASLD）是一种非常普遍的肝脏疾病，需要新的药物治疗来补充基于生活方式的干预措施。核受体激动剂一直作为潜在的药物靶点受到审视，截至目前，甲状腺激素受体β激动剂resmetirom是唯一获批的药物。双重过氧化物酶体增殖物激活受体α和δ激动剂elafibranor也进行了广泛的临床试验，该试验进入了III期临床试验，但未能证明对MASLD有有益作用。由于酒精性肝病和MASLD可能相互关联，elafibranor是否可能对酒精消费引起的肝病有效值得研究。小泉最近在《》上撰文报道，使用酒精性肝病小鼠模型，发现给予elafibranor可减轻肝脂肪变性、肝纤维化和肝细胞凋亡。尽管这些数据本质上是临床前的，但它们支持elafibranor在酒精性MASLD中的潜在有益作用，有必要在酒精性脂肪性肝病患者中对该分子进行测试。
