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Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis.
Metabolism ( IF 9.8 ) Pub Date : 2020-03-06 , DOI: 10.1016/j.metabol.2020.154203
Stergios A Polyzos 1 , Eun Seok Kang 2 , Chrysoula Boutari 3 , Eun-Jung Rhee 4 , Christos S Mantzoros 5
Affiliation  

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease and important unmet medical need. Current guidelines recommend, under specific restrictions, pioglitazone or vitamin E in patients with NASH and significant fibrosis, but the use of both remains off-label. We summarize evidence on medications for the treatment of nonalcoholic steatohepatitis (NASH), since NASH has been mainly associated with higher morbidity and mortality. Some of these medications are currently in phase 3 clinical trials, including obeticholic acid (a farnesoid X receptor agonist), elafibranor (a peroxisome proliferator activated receptor [PPAR]-α/δ dual agonist), cenicriviroc (a CC chemokine receptor antagonist), MSDC-0602 K (a PPAR sparing modulator), selonsertib (an apoptosis signal-regulating kinase-1 inhibitor) and resmetirom (a thyroid hormone receptor agonist). A significant research effort is also targeting PPARs and selective PPAR modulators, including INT131 and pemafibrate, with the expectation that novel drugs may have beneficial effects similar to those of pioglitazone, but without the associated adverse effects. Whether these and other medications could offer tangible therapeutic benefits, alone or in combination, apparently on a background of lifestyle modification, i.e. exercise and a healthy dietary pattern (e.g. Mediterranean diet) remain to be proven. In conclusion, major advances are expected for the treatment of NASH.

中文翻译:

用于治疗非酒精性脂肪性肝炎的当前和新兴药理学选择。

非酒精性脂肪肝疾病(NAFLD)是一种高度流行的疾病,也是尚未满足的重要医疗需求。当前的指南建议在特定的限制条件下,对患有NASH和严重纤维化的患者使用吡格列酮或维生素E,但仍不能使用两者。我们总结了用于治疗非酒精性脂肪性肝炎(NASH)的药物的证据,因为NASH主要与较高的发病率和死亡率相关。这些药物中的一些目前处于3期临床试验中,包括奥贝胆酸(一种法呢素X受体激动剂),elafibranor(一种过氧化物酶体增殖物激活受体[PPAR]-α/δ双激动剂),cenicriviroc(一种CC趋化因子受体拮抗剂), MSDC-0602 K(PPAR备用调制器),selonsertib(一种凋亡信号调节激酶-1抑制剂)和Resmetirom(一种甲状腺激素受体激动剂)。一项重要的研究工作还针对PPAR和选择性PPAR调节剂,包括INT131和匹马贝特,期望新型药物可能具有与吡格列酮相似的有益作用,但没有相关的不良作用。这些和其他药物能否单独或组合提供明显的治疗益处,显然是在改变生活方式的背景下进行的,即运动和健康的饮食习惯(例如地中海饮食)仍待证实。总之,NASH的治疗有望取得重大进展。期望新药可能具有与吡格列酮相似的有益作用,但没有相关的副作用。这些和其他药物能否单独或组合提供明显的治疗益处,显然是在生活方式改变的背景下进行的,即运动和健康的饮食习惯(例如地中海饮食)仍待证实。总之,NASH的治疗有望取得重大进展。期望新药可能具有与吡格列酮相似的有益作用,但没有相关的副作用。这些和其他药物能否单独或组合提供明显的治疗益处,显然是在生活方式改变的背景下进行的,即运动和健康的饮食习惯(例如地中海饮食)仍待证实。总之,NASH的治疗有望取得重大进展。
更新日期:2020-03-06
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