Weiskirchen Ralf, Weiskirchen Sabine, Tacke Frank
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Pauwelsstraße 30, Germany.
Department of Medicine III, RWTH University Hospital Aachen, D-52074 Aachen, Pauwelsstraße 30, Germany.
F1000Res. 2018 Jun 27;7. doi: 10.12688/f1000research.14841.1. eCollection 2018.
Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies.
肝纤维化的特征是过量纤维结缔组织的形成和沉积，导致进行性的组织结构重塑。无论潜在的有害触发因素如何，组织损伤都会引发涉及局部血管系统和免疫系统的炎症反应，以及内分泌和神经介质的全身动员，最终导致产生基质的细胞群体活化。遗传疾病、慢性病毒感染、酗酒、自身免疫攻击、代谢紊乱、胆汁淤积、胆汁酸成分或浓度改变、静脉阻塞和寄生虫感染都是导致肝纤维化的公认因素。此外，过量脂肪和其他引发内质网应激、线粒体功能改变、氧化应激以及微生物群改变的脂毒性介质与非酒精性脂肪性肝病相关，进而与肝纤维化的起始和进展有关。多学科专家小组制定了实践指南，包括针对特定肝病病因、纤维化阶段或与肝功能持续丧失相关的共病的首选治疗方法建议。在此，我们总结了导致肝纤维化的因素以及抗纤维化治疗的当前概念。
