Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.
J Dig Dis. 2018 Mar;19(3):118-126. doi: 10.1111/1751-2980.12584.
This review provides a personal view on anti-fibrosis therapy in the liver. The worst clinical consequence of liver fibrosis is the development of liver cirrhosis and portal hypertension. Etiology is a decisive factor which determines patterns of fibrous septa and subsequent vascular remodeling, which is essential for the development of portal hypertension. Removing or controlling the disease-causing agent, i.e. anti-viral treatment for hepatitis, is the essential first step for treating chronic liver diseases and can reverse fibrosis in some settings. However, removing etiology is not always sufficient to prevent fibrosis from progressing towards cirrhosis and portal hypertension. In liver diseases such as severe alcoholic hepatitis and massive parenchymal loss, the formation of vascular anastomoses between portal to central veins based on bridging fibrosis results in cirrhosis and portal hypertension. For these patients, anti-fibrotic treatment is crucial and urgent. Unfortunately, a lack of understanding how fibrosis contributes to vascular remodeling caused by and combined with a lack of suitable experimental models that recapitulate human liver diseases, has hampered the development of successful anti-fibrotic drugs for clinical use to date.
这篇综述提供了一个关于肝脏抗纤维化治疗的个人观点。肝脏纤维化的最严重临床后果是肝硬化和门静脉高压的发展。病因是决定纤维间隔和随后血管重塑模式的决定性因素，这对于门静脉高压的发展至关重要。消除或控制致病因素，即肝炎的抗病毒治疗，是治疗慢性肝病的基本第一步，在某些情况下可以逆转纤维化。然而，消除病因并不总是足以防止纤维化向肝硬化和门静脉高压进展。在严重酒精性肝炎和大量实质丧失等肝脏疾病中，基于桥接纤维化的门静脉到中央静脉之间的血管吻合形成导致肝硬化和门静脉高压。对于这些患者，抗纤维化治疗至关重要且紧迫。不幸的是，对纤维化如何导致血管重塑的理解不足，以及缺乏合适的实验模型来重现人类肝脏疾病，这阻碍了迄今为止用于临床的成功抗纤维化药物的发展。
