Current and future pharmacologic treatment of nonalcoholic steatohepatitis.
Current and future pharmacologic treatment of nonalcoholic steatohepatitis.
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DOI：
10.1097/mog.0000000000000356
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发表时间：
2017-05
影响因子：
2.5
通讯作者：
Sanyal AJ
中科院分区：
文献类型：
--
作者：
Banini BA;Sanyal AJ
非酒精性脂肪性肝炎（NASH）是非酒精性脂肪性肝病（NAFLD）的侵袭性形式，可在5-15%的患者中发展为肝硬化和肝细胞癌，并迅速成为终末期肝病的主要原因。饮食热量限制和运动，目前治疗NAFLD的基石，可能难以实现和维持，强调药物治疗的迫切需要。本文综述了目前用于治疗NAFLD的药物及其药理靶点。它还概述了目前正在开发的NAFLD药物。NASH的治疗可以大致分为两类，一类是针对驱动疾病发病机制的代谢扰动（如胰岛素抵抗和新生脂肪生成），另一类是针对下游过程，包括细胞应激、细胞凋亡、炎症和纤维化。调节过氧化物酶体增殖物-激活物受体、法氏体- x受体和胰高血糖素样肽1通路已被证明可改善肝脏组织学。肠道微生物组和代谢性内毒素血症是目前正在审查的新靶点。抗氧化剂（如维生素E）和最近的抗炎剂（如凋亡信号调节激酶1抑制剂）有望成为NASH的治疗方法。包括C-C趋化因子受体2型和5型拮抗剂在内的几种抗纤维化药物已被证明可抑制纤维化向肝硬化发展。目前有几种针对NASH的药物正在研发中。在未来几年内，NAFLD治疗方案的可用性有望遏制NAFLD相关终末期肝病的上升趋势。
Nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD), can progress to cirrhosis and hepatocellular cancer in 5–15% of patients and is rapidly becoming the leading cause for end-stage liver disease. Dietary caloric restriction and exercise, currently the cornerstone of therapy for NAFLD, can be difficult to achieve and maintain, underscoring the dire need for pharmacotherapy. This review presents the agents currently used in managing NAFLD and their pharmacologic targets. It also provides an overview of NAFLD agents currently under development. Therapies for NASH can be broadly classified into agents that target the metabolic perturbations driving disease pathogenesis (such as insulin resistance and de novo lipogenesis) and agents that target downstream processes including cell stress, apoptosis, inflammation, and fibrosis. Modulation of peroxisome proliferator-activator receptors, farnesoid-X-receptors, and the glucagon-like peptide 1 pathway have been shown to improve liver histology. The intestinal microbiome and metabolic endotoxemia are novel targets that are currently under review. Antioxidants such as vitamin E, and more recently anti-inflammatory agents such as apoptosis signal-regulating kinase 1 inhibitors show promise as therapy for NASH. Several antifibrotic agents including C-C chemokine receptor type 2 and type 5 antagonists have been shown to inhibit the progression of fibrosis toward cirrhosis. There are currently several agents in the drug pipeline for NASH. Within the next few years, the availability of therapeutic options for NAFLD will hopefully curb the rising trend of NAFLD-related end stage liver disease.