https://scholars.lib.ntu.edu.tw/handle/123456789/144524
標題: | 慢性C型肝炎併肝硬化病人對抗病毒治療反應低之機轉 | 作者: | 賴明陽 | 公開日期: | 2003 | 出版社: | 臺北市:國立臺灣大學醫學院臨床醫學研究所 | 摘要: | Chronic hepatitis C virus ( HCV ) infection can lead to liver cirrhosis in 20-30% of patients, which predisposes to hepatic decompensation and hepatocellular carcinoma ( HCC ). These hepatitis C patients with cirrhosis are associated with lower response rates to either interferon alfa monotherapy or combination therapy with interferon and ribavirin, about 50% or less of that in non-cirrhotic patients. The mechanism for the difference in response rates between non-cirrhotic and cirrhotic HCV-infected patients, however, is unclear. It is most likely that both host and viral factors are important.The hypothesis was : The poor response to interferon and interferon/ribavirin therapy in patients with chronic hepatitis C and cirrhosis is related to the impaired interferon alfa signaling pathways, which are interfered by structural changes in hepatocytes induced by prolonged necro-inflammation and/or factors associated with the cirrhotic process. The specific aims were : 1. To compare the gene expressions of JAK-STAT signaling pathways of interferon alfa in liver tissues obtained from chronic hepatitis C patients with or without cirrhosis. 2. To examine whether the expression of inhibitory factors for the JAK-STAT signaling pathway are increased in HCV-infected cirrhotic liver, including suppressor of cytokine signaling ( SOCS ) family. 3. To compare the expression of interferon-induced PKR ( double stranded RNA-activated protein kinase ) and OAS ( 2’-5’ oligoadenylate synthetase ) between HCV-related cirrhotic or non-cirrhotic liver. We found that in cirrhotic liver with chronic hepatitis C, STAT 1 phosphorylated forms ( phosphorylation at Tyr-701 ) and STAT 3 phosphorylated forms (phosphorylation at Tyr-705 ) were increased compared with liver tissue from non-cirrhotic liver with chronic hepatitis C. Expression of both SOCS1 and SOCS 3 increased in cirrhotic liver. Unexpctedly, IL6 expression did not increase in cirrhotic liver tissues. The expressions of phosphorylated forms of PKR was increased in the cirrhotic liver with chronic hepatitis C. Our study support that SOCS 1 and SOCS 3 may be related to the low sustained response to interferon-base therapy in chronic hepatitis C patients with cirrhosis. To decrease or inhibit the expressions of SOCS-1 and SOCS-3 may increase the sustained viral response to interferon-base therapy for patients with chronic hepatitis C. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/27492 | 其他識別: | 912315B002014 | Rights: | 國立臺灣大學醫學院臨床醫學研究所 |
顯示於: | 臨床醫學研究所 |
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912315B002014.pdf | 41.74 kB | Adobe PDF | 檢視/開啟 |
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