Université de Strasbourg, 67000 Strasbourg, France.
Institut de Recherche sur les Maladies Virales et Hépatiques U1110, 67000 Strasbourg, France.
Cells. 2020 Apr 3;9(4):875. doi: 10.3390/cells9040875.
Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.
由于病毒性或代谢性慢性肝脏疾病引起的肝纤维化是全球健康的主要挑战。与肝病进展相关，纤维化是肝病结局和肝细胞癌 (HCC) 风险的关键因素。尽管原发性肝损伤的机制不同，且疾病特异性细胞反应不同，但纤维化性肝病的进展在主要肝脏疾病病因中具有共同模式。过去十年中的科学发现改变了对肝纤维化机制的理解。去除病因，如控制或治愈病毒感染，已表明肝纤维化是可逆转的。然而，逆转通常发生得太慢或太不频繁，无法避免危及生命的并发症，特别是在晚期纤维化中。因此，对于抗纤维化疗法以预防肝病进展和 HCC 发展存在巨大的未满足的医疗需求。然而，尽管许多抗纤维化候选药物在实验动物模型中显示出强大的效果，但它们在临床试验中的抗纤维化效果有限或不存在。因此，尚无针对肝纤维化的批准疗法。在这篇综述中，我们总结了慢性肝脏疾病中纤维化发生的细胞驱动因素和分子机制，并讨论了它们对开发迫切需要的抗纤维化疗法的影响。
