Kountouras J, Zavos C, Chatzopoulos D
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
J Viral Hepat. 2003 Sep;10(5):335-42. doi: 10.1046/j.1365-2893.2003.00452.x.
The apoptotic process appears to be a host defence mechanism against viral infections and tumourigenesis. However, many viral genomes encode proteins, which repress apoptosis so as to escape from immune attack by the host. Therefore, virus-host interactions may determine viral persistence, extent and severity of liver inflammation and possibly viral hepatocarcinogenesis. Apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C. Pathomorphologic features of increased apoptosis include shrinkage and fragmentation of nuclei/cytoplasm in piecemeal necrosis areas, acidophilic bodies, and focal cell dropout in the liver lobule. The hepatitis C virus (HCV) core protein exhibits both proapoptotic or antiapoptotic actions. Modulation of apoptosis may involve binding of HCV core protein to the intracellular signal transducing portion of death receptors and displacement of signalling molecules. Apoptosis may occur in the absence of significant transaminase elevation, thereby explaining the lack of correlation between biochemical activity and liver cell histological injury. Monitoring caspase activation might provide a reliable tool to estimate the efficacy of HCV therapy, and might open challenging therapeutic strategies in HCV infection. The antiviral effect of interferon may be mediated through induction of apoptosis. Lastly, administration of the antiapoptotic ursodeoxycholic acid in HCV infection is compatible with the notion that apoptosis may represent a mechanism for viral shedding rather than for viral elimination, thereby raising the concept that inhibition of apoptosis could ameliorate hepatitis C.
凋亡过程似乎是一种针对病毒感染和肿瘤发生的宿主防御机制。然而，许多病毒基因组编码蛋白质，这些蛋白质抑制凋亡以便逃避宿主的免疫攻击。因此，病毒与宿主的相互作用可能决定病毒的持续存在、肝脏炎症的程度和严重性，以及可能的病毒性肝癌发生。肝细胞凋亡可能在丙型肝炎发病机制中起重要作用。凋亡增加的病理形态学特征包括碎片状坏死区域细胞核/细胞质的皱缩和碎裂、嗜酸性小体以及肝小叶内的局灶性细胞脱落。丙型肝炎病毒（HCV）核心蛋白具有促凋亡或抗凋亡作用。凋亡的调节可能涉及HCV核心蛋白与死亡受体的细胞内信号转导部分结合以及信号分子的置换。凋亡可能在转氨酶无显著升高的情况下发生，从而解释了生化活性与肝细胞组织学损伤之间缺乏相关性。监测半胱天冬酶激活可能提供一种可靠的工具来评估HCV治疗的疗效，并可能为HCV感染开辟具有挑战性的治疗策略。干扰素的抗病毒作用可能通过诱导凋亡来介导。最后，在HCV感染中给予抗凋亡的熊去氧胆酸与凋亡可能代表病毒释放而非病毒清除机制的观点相符，从而提出抑制凋亡可改善丙型肝炎的概念。
