Pathobiology of liver fibrosis: a translational success story.
Pathobiology of liver fibrosis: a translational success story.
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DOI：
10.1136/gutjnl-2014-306842
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发表时间：
2015-05
期刊：
影响因子：
24.5
通讯作者：
Friedman SL
中科院分区：
文献类型：
--
作者：
Lee YA;Wallace MC;Friedman SL
B型或C型肝炎抗病毒治疗后肝纤维化和肝硬化的可逆性推进了慢性肝病患者，特别是非酒精性脂肪性肝炎患者抗纤维化治疗的前景。纤维化的机制集中在肝星状细胞上，其在损伤期间通过“激活”成为纤维化肌成纤维细胞，并且处于努力定义新的药物靶点的关系中。最近的研究已经阐明了星状细胞基因调控和表观遗传学的途径，通过招募和扩增纤维溶解性巨噬细胞，离散的炎症细胞亚群的细微反应和鉴定的“导管反应”作为严重损伤和修复的标志物的纤维化消退的新兴途径。基于我们对纤维化发病机制的广泛了解，现在的注意力集中在抗纤维化治疗策略以及使用这些药物进行临床试验的监管挑战上。新的疗法正在尝试：1）控制或治愈原发性疾病或减少组织损伤; 2）靶向受体-配体相互作用和细胞内信号传导; 3）抑制纤维化发生;和4）促进纤维化的消退。目前迫切需要在验证纤维化进展和消退的非侵入性标志物方面取得进展，以取代活检并缩短临床试验的持续时间。科学和临床挑战仍然存在，然而，过去三十年来在理解肝纤维化方面的稳步进展促成了一个新兴的转化成功故事，在不久的将来，抗纤维化疗法治疗慢性肝病患者的希望是现实的。
Reversibility of hepatic fibrosis and cirrhosis following antiviral therapy for hepatitis B or C has advanced the prospect of developing antifibrotic therapies for patients with chronic liver diseases, especially non-alcoholic steatohepatitis. Mechanisms of fibrosis have focused on hepatic stellate cells, which become fibrogenic myofibroblasts during injury through ‘activation’, and are at the nexus of efforts to define novel drug targets. Recent studies have clarified pathways of stellate cell gene regulation and epigenetics, emerging pathways of fibrosis regression through the recruitment and amplification of fibrolytic macrophages, nuanced responses of discrete inflammatory cell subsets and the identification of the ‘ductular reaction’ as a marker of severe injury and repair. Based on our expanded knowledge of fibrosis pathogenesis, attention is now directed towards strategies for antifibrotic therapies and regulatory challenges for conducting clinical trials with these agents. New therapies are attempting to: 1) Control or cure the primary disease or reduce tissue injury; 2) Target receptor-ligand interactions and intracellular signaling; 3) Inhibit fibrogenesis; and 4) Promote resolution of fibrosis. Progress is urgently needed in validating non-invasive markers of fibrosis progression and regression that can supplant biopsy and shorten the duration of clinical trials. Both scientific and clinical challenges remain, however the past three decades of steady progress in understanding liver fibrosis have contributed to an emerging translational success story, with realistic hopes for antifibrotic therapies to treat patients with chronic liver disease in the near future.
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影响因子：
13.5
作者：
DeLeve, Laurie D.
通讯作者：
DeLeve, Laurie D.
影响因子：
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作者：
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作者：
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通讯作者：
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