Reversal of hepatic fibrosis - Fact or fantasy?
Reversal of hepatic fibrosis - Fact or fantasy?
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DOI：
10.1002/hep.20974
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发表时间：
2006-02-01
期刊：
影响因子：
13.5
通讯作者：
Bansal, MB
中科院分区：
文献类型：
--
作者：
Friedman, SL;Bansal, MB
逆转肝纤维化的前景已经引起了人们的极大兴趣，因为基础科学的进步正在转化为有希望的新的抗纤维化疗法。既要承认为这些成功创造了框架的历史进步，也要认识到肝病在传播这些成功方面所发挥的重要作用。一种紧迫感支撑着这一努力，因为丙型肝炎和非酒精性肝炎的流行正变得与进展的纤维化有关。为了保持进展，并将研究人员和临床医生之间的困惑降至最低，有必要标准化涉及纤维化“逆转”和“退化”的术语。还必须迅速优化非侵入性纤维化标志物，以缓解目前进行临床试验的瓶颈。在确定纤维化的遗传决定因素方面的进展可能会进一步完善临床试验的患者选择，缩短试验持续时间，并发现科学研究的新方向。对成功的抗纤维化治疗的现实期望反映了有效治疗病毒性肝病的患者纤维化消退的确凿证据，以及对细胞外基质产生和降解机制的理解日益清晰。星状细胞激活和凋亡的范式分别为理解肝纤维化形成和纤维化消退的途径提供了有价值的框架。为了确定纤维化可逆性的决定因素和动力学，发现更多的抗纤维化治疗靶点，以及开发定制的多药方案，持续的进展是必不可少的。这些进展肯定会在未来25年内被肝病学捕捉到，并深刻影响慢性肝病患者的预后。
The prospect of reversing hepatic fibrosis has generated great interest now that basic science advances are being translated into promising new antifibrotic therapies. It is appropriate to recognize both the historical advances that created the framework for these successes, anti the important role that HEPATOLOGY has played in disseminating them. A sense of urgency underlies this effort as the epidemics of HCV and NASH are becoming associated with advancing fibrosis. To maintain progress and minimize confusion among investigators and clinicians it is essential to standardize terms referring to fibrosis 'reversal' and 'regression.' There must also be rapid optimization of non-invasive markers of fibrosis to relieve this current bottleneck to conducting clinical trials. Progress in identifying genetic determinants of fibrosis could further refine patient selection for clinical trials and shorten their duration, as well as unearthing new directions of scientific inquiry. Realistic expectations for successful anti-fibrotic therapies reflect solid evidence of fibrosis regression in patients treated effectively for viral liver disease, as well as growing clarity in the understanding mechanisms of extracellular matrix production and degradation. The paradigms of stellate cell activation and apoptosis remain valuable frameworks for understanding pathways of hepatic fibrogenesis and fibrosis regression, respectively. Continued progress is essential in order to identify the determinants and dynamics of fibrosis reversibility, to discover additional targets for anti-fibrotic therapy, and to develop customized multi-drug regimens. These advances are sure to be captured in the next 25 years by HEPATOLOGY, and to profoundly impact the prognosis of patients with chronic liver disease.