慢性C型肝炎併肝硬化病人對抗病毒治療反應低之機轉
Date Issued
2003
Date
2003
Author(s)
賴明陽
DOI
912315B002014
Abstract
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.
SDGs
Publisher
臺北市：國立臺灣大學醫學院臨床醫學研究所
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
912315B002014.pdf
Size
41.74 KB
Format
Adobe PDF
Checksum
(MD5):81bf79a8d80b5bf53a3c016a5412d2f3