Khaznadar Farah, Khaznadar Omar, Petrovic Ana, Hefer Marija, Gjoni Fabian, Gjoni Stefan, Steiner Justinija, Smolic Martina, Bojanic Kristina
Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Curr Issues Mol Biol. 2024 Jun 21;46(7):6300-6314. doi: 10.3390/cimb46070376.
With around one billion of the world's population affected, the era of the metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which to date there are almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it also affects extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn) was approved for metabolic-dysfunction-associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Although the pharmaceutical industry is still lagging behind in developing an approved pharmacologic therapy for MAFLD, research has recently intensified and many molecules which are in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was approved via accelerated procedure for treatment of MAFLD, i.e., of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval.
全球约有10亿人口受到影响，代谢相关脂肪性肝病（MAFLD）大流行时代已步入全球舞台。MAFLD是一种慢性进行性肝病，伴有2型糖尿病和肥胖症等代谢紊乱，可无症状地进展为肝硬化，继而发展为肝细胞癌（HCC），而迄今为止几乎没有获批的药物治疗选择。由于MAFLD病因非常复杂，且还会影响肝外器官，因此在寻找有效且安全的MAFLD治疗活性物质时需要采用多学科方法。治疗MAFLD的最佳药物应减少肝脏中的脂肪变性、纤维化和炎症，而MAFLD药物获批的优胜者似乎是能显著改善肝脏组织学的药物。2020年，司美格鲁扎（Lipaglyn）在印度被批准用于治疗代谢功能障碍相关脂肪性肝炎（MASH）；然而，该药物仍在其他国家进行研究。尽管制药行业在开发获批的MAFLD药物治疗方面仍滞后，但最近研究力度加大，许多处于临床试验最后阶段的分子有望在未来几年获批。今年，美国首款药物（Rezdiffra™）已通过加速程序获批用于治疗MAFLD，即成人MASH。本综述强调了与MAFLD治疗药物开发相关的最新信息，重点关注最接近获批的分子。
