Fiorucci Stefano, Biagioli Michele, Distrutti Eleonora
University of Perugia, Department Surgical and Biomedical Sciences, Perugia, Italy.
University of Perugia, Department Surgical and Biomedical Sciences, Perugia, Italy.
Pharmacol Res. 2018 Aug;134:289-298. doi: 10.1016/j.phrs.2018.07.014. Epub 2018 Jul 17.
With an estimated prevalence of ≈25% in Western and Asian countries, non alcoholic fatty liver disease (NAFLD), caused by chronic excessive caloric intake, is the emerging as the most prevalent liver disorder worldwide. NAFLD exists in two clinical entities, non-alcoholic fatty liver disease (NAFL), a relative benign disease that carry on minimal risk of liver-related morbidity but significant risk of cardiovascular complications, and non-alcoholic steatohepatitis (NASH), a progressive liver disorder with a significant risk for development of liver-related morbidities and mortality. While, liver injury in NASH is contributed by lipid overload in hepatocytes, lipotoxicity, the main determinant of disease progression is an inflammation-driven fibrotic response. Here, we review the landscape of emerging pharmacological interventions in the treatment of NAFL and NASH. A consensus exists that, while treating the liver component of NASH requires development of novel pharmacological approaches, the future therapy of NASH needs to be tailored to the single patient and most likely will be a combination of agents acting on specific pathogenic mechanisms at different disease stage.
在西方国家和亚洲国家,非酒精性脂肪性肝病(NAFLD)的估计患病率约为25%,它由长期热量摄入过多引起,正成为全球最普遍的肝脏疾病。NAFLD有两种临床类型,即非酒精性脂肪肝(NAFL),这是一种相对良性的疾病,肝脏相关发病风险较低,但心血管并发症风险较高;以及非酒精性脂肪性肝炎(NASH),这是一种进行性肝脏疾病,有显著的肝脏相关发病和死亡风险。虽然NASH中的肝损伤是由肝细胞脂质过载导致的,但脂毒性是疾病进展的主要决定因素,是一种炎症驱动的纤维化反应。在此,我们综述了治疗NAFL和NASH的新兴药物干预情况。人们已达成共识,虽然治疗NASH的肝脏病变需要开发新的药物方法,但NASH的未来治疗需要根据个体患者量身定制,很可能是在不同疾病阶段作用于特定致病机制的药物组合。