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标题: 关于抗纤维化治疗最新进展的最新进展 [打印本页]

作者: StephenW    时间: 2018-10-4 20:55     标题: 关于抗纤维化治疗最新进展的最新进展

An update on the recent advances in antifibrotic therapy
Frank Tacke & Ralf Weiskirchen ORCID Icon
Received 09 May 2018, Accepted 26 Sep 2018, Accepted author version posted online: 27 Sep 2018, Published online: 03 Oct 2018

    Download citation https://doi.org/10.1080/17474124.2018.1530110



ABSTRACT

Introduction: Chronic injury to the liver, such as viral hepatitis, alcoholism, non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), promotes extracellular matrix deposition and organ scarring, termed hepatic fibrosis. Fibrosis might progress to cirrhosis and predisposes to hepatocellular carcinoma (HCC), but is also associated with extrahepatic morbidity and mortality in NAFLD/NASH. The improved understanding of pathogenic mechanisms underlying chronic inflammation and fibrogenesis in the liver prompted recent advances in antifibrotic therapies.

Areas covered: We review recent advances in antifibrotic therapy, of which most are currently tested in clinical trials for NAFLD or NASH. This explains the manifold metabolic pathways as antifibrotic targets, including farnesoid X receptor (FXR) agonism (obeticholic acid, nonsteroidal FXR agonists), acetyl-CoA carboxylase inhibition, peroxisome proliferator-activator receptor agonism (elafibranor, lanifibranor, saroglitazar), and fibroblast growth factor (FGF)-21 or FGF-19 activation. Other antifibrotic drug candidates target cell death or inflammation, such as caspase (emricasan) or ASK1 inhibitors (selonsertib), galectin-3 inhibitors and reducing inflammatory macrophage recruitment by blocking chemokine receptors CCR2/CCR5 (cenicriviroc).

Expert commentary: The tremendous advances in translational and clinical research fuels the hope for efficacious antifibrotic therapies within the next 5 years. Very likely, a combination of etiology-specific, metabolic, anti-inflammatory, and direct antifibrotic interventions will be most effective.
KEYWORDS: Liver fibrosis, macrophages, chemokine, matrix, regression, NAFLD/NASH, translational medicine, hepatic stellate cell, myofibroblast, gut-liver axis, microbiome
作者: StephenW    时间: 2018-10-4 20:55

关于抗纤维化治疗最新进展的最新进展
Frank Tacke和Ralf Weiskirchen ORCID Icon
2018年5月9日收到,2018年9月26日接受,接受作者版本在线发布:2019年9月27日,在线发布:2018年10月3日

    下载引文https://doi.org/10.1080/17474124.2018.1530110



抽象

简介:慢性肝损伤,如病毒性肝炎,酒精中毒,非酒精性脂肪性肝病(NAFLD)或非酒精性脂肪性肝炎(NASH),促进细胞外基质沉积和器官瘢痕形成,称为肝纤维化。纤维化可能发展为肝硬化并易患肝细胞癌(HCC),但也与NAFLD / NASH中的肝外发病率和死亡率相关。对肝脏中慢性炎症和纤维发生的致病机制的改进理解促使抗纤维化疗法的最新进展。

涵盖的领域:我们回顾了抗纤维化治疗的最新进展,其中大多数目前在NAFLD或NASH的临床试验中进行了测试。这解释了作为抗纤维化靶标的多种代谢途径,包括法尼醇X受体(FXR)激动剂(obeticholic acid,非甾体FXR激动剂),乙酰辅酶A羧化酶抑制剂,过氧化物酶体增殖物激活剂受体激动剂(elafibranor,lanifibranor,saroglitazar)和成纤维细胞生长。因子(FGF)-21或FGF-19活化。其他抗纤维化药物候选物靶向细胞死亡或炎症,例如半胱天冬酶(emricasan)或ASK1抑制剂(selonsertib),半乳糖凝集素-3抑制剂和通过阻断趋化因子受体CCR2 / CCR5(cenicriviroc)来减少炎性巨噬细胞募集。

专家评论:转化和临床研究的巨大进步为未来5年内有效的抗纤维化治疗提供了希望。很可能,病因特异性,代谢性,抗炎性和直接抗纤维化干预的组合将是最有效的。
关键词:肝纤维化,巨噬细胞,趋化因子,基质,消退,NAFLD / NASH,转化医学,肝星状细胞,肌成纤维细胞,肠肝轴,微生物组
作者: 齐欢畅    时间: 2018-10-4 21:36

不错
作者: sky8989    时间: 2018-10-4 23:46

回复 StephenW 的帖子

纤维化也能治愈,太好了
作者: 齐欢畅    时间: 2018-10-4 23:51

sky8989 发表于 2018-10-4 23:46
回复 StephenW 的帖子

纤维化也能治愈,太好了

好消息啊
作者: sky8989    时间: 2018-10-5 00:01

兴奋啊




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