2012病毒性肝炎教学幻灯1.pptVIP

* Hepatitis C Disease Pathogenesis Once a virus has achieved entry into the cell, the cellular immune system is the dominant means of limitation of viral spread. By virtue of their capacity to produce cytokines, CD4+ cells play a central role in the control of immune responses. Studies have been published on the pattern of CD4+ responses in those few subjects who have complete virologic recovery after HCV infection. Quantitatively, subjects who have a strong, polyclonal proliferative response to HCV antigens are able to clear HCV after acute infection and clear viremia after IFN therapy. The cytokines produced by these CD4+ cells are generally type I (IFN gamma and tumor necrosis factor [TNF] alfa), suggesting that cellular immune responses typically mediated by these cytokines are critical to resolution of infection. * This slide illustrates the natural history of chronic HCV infection over a 50-year time period. The course of the disease is variable. It can be nonprogressive and mild, it can be slowly progressive, it can be associated with marked extrahepatic manifestations, or it can be rapidly progressive leading to cirrhosis and HCC. Further, chronic hepatitis C is often silent, with no symptoms until advanced disease develops. During chronic infection, there can be a slow and progressive worsening of fibrosis to from none to stage 4 (cirrhosis). HCC typically develops only after decades of infection in patients with underlying cirrhosis. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology. 2002;36:S21-S29. * * * * 在报告研究结果之前，让我们先来复习一下乙肝感染的病程发展及其危害性。 高达 95%婴儿期急性乙肝感染者会发展成慢性乙肝，成年期感染者这种情况约3-5%。1 慢性乙肝5年内有12-20%进展成为肝硬化，而肝硬化患者5年内有6-15 %发生肝细胞癌。据统计，乙肝表面抗原阳性者较常人患肝癌的危险性高出100倍2。 婴儿期感染者比成年感染者患肝癌的危险更高，最终有高达40%的婴儿期感染者发生肝癌。2 慢性肝炎和肝硬化的患者肝癌的发病率最高。1另一部分肝硬化患者5年内有20-23%进展为肝衰竭，需进行肝移植。 References 1. Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: 1733–45. 2. Chu C-M. Towards control of hepatitis B in the Asia-Pacific region: natural history of chron