Pár Alajos, Wittmann István, Pár Gabriella
1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Klinikai Központ, I. Belgyógyászati Klinika Pécs, Ifjúság u. 13., 7624 Magyarország.
2 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Klinikai Központ, II. Belgyógyászati Klinika és Nephrológiai, Diabetológiai Centrum Pécs Magyarország.
Orv Hetil. 2022 May 29;163(22):855-862. doi: 10.1556/650.2022.32480.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Non-alcoholic steatohepatitis (NASH), the aggressive form of NAFLD can progress to cirrhosis, and is becoming the leading cause of end-stage liver disease. NAFLD and NASH are prevalent in obese individuals and frequently coexist with type 2 diabetes mellitus as well as cardiovascular and renal complications. There is no approved therapy for the treatment of NAFLD and NASH. Their current management focuses on controlling risk factors, and lifestyle modification, weight reduction, caloric restriction, diet and exercise, but these can be difficult to achieve and maintain. Thus, there is an urgent need for effective pharmacotherapy. This review summarizes pharmacological agents available to treat diabetes mellitus, the main risk factor of NAFLD, drugs that could potentially be useful also for the therapy of NASH. Furthermore, we describe novel therapies targeting different pathogenic pathways of NAFLD, several agents that are under development specifically for the treatment of NASH. These new classes of medications may target hepatic fat accumulation, de novo lipogenesis, farnesoid X receptor-bile acid axis, oxidative stress, inflammation, gut microbiome and fibrogenesis. Until now, the use of pioglitazone and vitamin E has only been recommended by guidelines for selected patient groups with biopsy-proven NASH. It is likely that in the future, the combination of different types of targeted pharmacotherapies will provide an effective treatment for NASH. Since NAFLD is a systemic metabolic disease, cooperation between diabetologists, nephrologists, cardiologists and hepatologists is also highly advised in the management of these patients.
非酒精性脂肪性肝病(NAFLD)是最常见的肝脏疾病。非酒精性脂肪性肝炎(NASH)是NAFLD的侵袭性形式,可进展为肝硬化,正成为终末期肝病的主要原因。NAFLD和NASH在肥胖个体中普遍存在,且常与2型糖尿病以及心血管和肾脏并发症并存。目前尚无获批用于治疗NAFLD和NASH的疗法。其当前的管理重点是控制危险因素、改变生活方式、减轻体重、限制热量摄入、饮食和运动,但这些措施难以实现和维持。因此,迫切需要有效的药物治疗。本综述总结了可用于治疗糖尿病(NAFLD的主要危险因素)的药物,这些药物可能对NASH的治疗也有用。此外,我们描述了针对NAFLD不同致病途径的新型疗法,几种专门用于治疗NASH的正在研发的药物。这些新型药物可能针对肝脏脂肪堆积、从头脂肪生成、法尼醇X受体-胆汁酸轴、氧化应激、炎症、肠道微生物群和纤维化形成。到目前为止,仅对经活检证实为NASH的特定患者群体,指南才推荐使用吡格列酮和维生素E。未来,不同类型的靶向药物治疗联合使用可能会为NASH提供有效的治疗方法。由于NAFLD是一种全身性代谢疾病,在这些患者的管理中,强烈建议糖尿病专家、肾病专家、心脏病专家和肝病专家之间进行合作。