Sumida Yoshio, Seko Yuya, Yoneda Masashi
Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan.
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hepatol Res. 2017 Mar;47(4):266-280. doi: 10.1111/hepr.12856. Epub 2017 Feb 13.
Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin, weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to lack of clinical evidence. The effects of pioglitazone on NASH histology with T2DM have been extensively proved, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. In recent years, novel antidiabetic medications have been approved for T2DM, such as glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium/glucose cotransporter 2 inhibitors. A key clinical question for hepatologists is what kinds of antidiabetic medications are the most appropriate for the treatment of NAFLD accompanied by T2DM, to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increased risk of cardiovascular events. This review focuses on novel antidiabetic agents and future perspectives on the treatment of NAFLD/NASH with T2DM.
在日本，肝脏相关疾病是2型糖尿病（T2DM）患者的主要死因。2型糖尿病与非酒精性脂肪性肝病（NAFLD）密切相关，非酒精性脂肪性肝病是全球最常见的慢性肝病。非酒精性脂肪性肝炎（NASH）是NAFLD的一种严重形式，可导致肝细胞癌和肝衰竭。非酒精性脂肪性肝炎可被称为“糖尿病性肝病”。目前尚无针对合并T2DM的NAFLD/NASH患者的确立的药物治疗方法。尽管二甲双胍被确立为T2DM的一线治疗药物，鉴于其相对安全性以及对糖化血红蛋白、体重和心血管死亡率的有益影响，但由于缺乏临床证据，不推荐将该药物作为NASH/NAFLD的特异性治疗药物。吡格列酮对合并T2DM的NASH组织学的影响已得到广泛证实，但也存在一些问题，如体重增加、液体潴留、癌症发病率和骨折。近年来，新型抗糖尿病药物已被批准用于治疗T2DM，如胰高血糖素样肽1受体激动剂、二肽基肽酶4抑制剂和钠/葡萄糖协同转运蛋白2抑制剂。肝病学家面临的一个关键临床问题是，哪种抗糖尿病药物最适合治疗合并T2DM的NAFLD，以预防肝纤维化进展导致HCC/肝脏相关死亡率，同时又不增加心血管事件的风险。本综述重点关注新型抗糖尿病药物以及合并T2DM的NAFLD/NASH治疗的未来展望。
