Hepatology Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy.
Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Cells. 2023 Jun 24;12(13):1712. doi: 10.3390/cells12131712.
Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the onset of chronic liver disease, and its propagation promotes liver dysfunction. At the same time, chronic liver disease is characterized by alterations in primary and secondary hemostasis but unlike previously thought, these changes are not associated with an increased risk of bleeding complications. In recent years, the role of coagulation imbalance has been postulated as one of the main mechanisms promoting hepatic fibrogenesis. In this review, we aim to investigate the function of microvascular thrombosis in the progression of liver disease and highlight the molecular and cellular networks linking hemostasis to fibrosis in this context. We analyze the predictive and prognostic role of coagulation products as biomarkers of liver decompensation (ascites, variceal hemorrhage, and hepatic encephalopathy) and liver-related mortality. Finally, we evaluate the current evidence on the application of antiplatelet and anticoagulant therapies for prophylaxis of hepatic decompensation or prevention of the progression of liver fibrosis.
纤维化是慢性炎症不可避免的后果。成纤维细胞受到多种途径的刺激,导致细胞外基质沉积,这是慢性肝病发病的第一步,其传播促进肝功能障碍。同时,慢性肝病的特点是主要和次要止血的改变,但与以前的观点不同,这些变化与出血并发症风险的增加无关。近年来,凝血失衡的作用被认为是促进肝纤维化的主要机制之一。在这篇综述中,我们旨在研究微血管血栓形成在肝病进展中的作用,并强调止血与纤维化之间的分子和细胞网络。我们分析了凝血产物作为肝失代偿(腹水、静脉曲张出血和肝性脑病)和肝相关死亡率的预测和预后标志物的作用。最后,我们评估了抗血小板和抗凝治疗预防肝失代偿或阻止肝纤维化进展的应用的现有证据。