Anti-fibrotic therapy: Lost in translation?
Anti-fibrotic therapy: Lost in translation?
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DOI：
10.1016/s0168-8278(12)60008-7
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发表时间：
2012-01-01
影响因子：
25.7
通讯作者：
Pinzani, Massimo
中科院分区：
文献类型：
--
作者：
Schuppan, Detlef;Pinzani, Massimo
虽然潜在的抗纤维化药物的临床前开发已经非常先进，拥有众多的药理靶点和有希望的药物，但几乎没有一种进入临床验证。原因是多方面的，包括通常进展缓慢的肝纤维化，当使用传统的基于肝活检的参数或硬肝相关终点时，需要大量分层良好的患者接受长期治疗。重要的是，众所周知，肝纤维化进展或消退缺乏敏感和特异的替代标记物或成像技术，使快速临床筛查潜在的抗纤维化药物成为可能。尽管如此，鉴于对积极影响慢性肝病发病率和死亡率的抗纤维化药物的迫切需求，该领域现在正更快地转向临床翻译。这一发展是由深思熟虑的临床前验证、更好的研究设计和使用当前可用的方法改进的替代读数推动的。此外，即将到来的新型生物标志物和成像技术将很快允许对纤维化进展和消退进行更准确和有效的评估。
While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver-related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need for anti-fibrotics that positively impact morbidity and mortality from chronic liver diseases, the field is now moving more quickly towards clinical translation. This development is driven by thoughtful preclinical validation, a better study design and improved surrogate readouts using currently available methodologies. Moreover, upcoming novel biomarkers and imaging technologies will soon permit a more exact and efficient assessment of fibrosis progression and regression.