Debes Jose D, Bohjanen Paul R, Boonstra Andre
Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN, USA.
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
J Clin Transl Hepatol. 2016 Dec 28;4(4):328-335. doi: 10.14218/JCTH.2016.00034. Epub 2016 Nov 21.
With the introduction of antiretroviral therapy (ART), a dramatic reduction in HIV-related morbidity and mortality has been observed. However, it is now becoming increasingly clear that liver-related complications, particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself, are of serious concern to HIV patients. The pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication, and bacterial translocation lead to chronic immune activation and inflammation, which ART is unable to fully suppress, promoting production of fibrinogenic mediators and fibrosis. In addition, mitochondrial toxicity, triggered by both ART and HIV, contributes to intrahepatic damage, which is even more severe in patients co-infected with viral hepatitis. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV has been obtained, and these are detailed and discussed in this review.
随着抗逆转录病毒疗法(ART)的引入,已观察到与HIV相关的发病率和死亡率大幅下降。然而,现在越来越清楚的是,肝脏相关并发症,特别是ART以及慢性HIV感染本身导致的快速纤维化发展,是HIV患者严重关注的问题。HIV患者肝纤维化的病理生理学是一个多因素过程,持续性病毒复制和细菌易位导致慢性免疫激活和炎症,而ART无法完全抑制这种炎症,从而促进纤维蛋白原介质的产生和纤维化。此外,ART和HIV引发的线粒体毒性会导致肝内损伤,在合并病毒性肝炎感染的患者中这种损伤更为严重。近年来,已获得了关于HIV中加速纤维化和肝病进展机制的新见解,本综述将对这些见解进行详细阐述和讨论。