Alterations of NS5 region of hepatitis C virus in patients with chronic hepatitis C and response to ribavirin plus ∝-interferon therapy

• Main Authors: Huang,Chun-fang, 黃純芳
• Other Authors: Lai,Ming-yang
• Format: Others
• Language: zh-TW
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/07351184755228579781

碩士 === 國立臺灣大學 === 分子醫學研究所 === 83 === Individuals infected by hepatitis C virus often evolve into chronic hepatitis C, and liver cirrhosis or hepatocellular carcinoma may develop later.Currently, the only approved treatment of chronic hepatitis C is the recombinant α interferon Unfortunately, the outcome of the treatment is poor. An interferon sensitivity determining region(ISDR) in the NS5A region is claimed to be correlate with the treatment outcome. A recent important advance in the treatment of chronic hepatitis C is that the combination of interferon α and ribavirin lead to a much better result. The mechanisms of how ribavirin works and how these two drugs cooperate are still unknown. To understand how combination therapy take effect, we examinedHCV NS5B region, whose product is a RNA dependent RNS polymerase and is a possible candidate as the target site of ribavirin, from the pre- treatment serum of 5 responders and 5 non-responders. Serum samples at the end of 24-week therapy and at the end of 6 months after treatment cessation from these non responders are also examined by RT-PCR and direct sequencing.Using the same methods, pre treatment serums of 11 responders and 7 non- responders of the combination therapy were analyzedto check the mutations in the ISDR of the NS5A region.We found that the occurence of mutations in the NS5B region tended to be more frequent in the pre-treatment samples from nonresponders; and the mutation rate of amino acids 2470, 2843,2955 are significantly different among responders and nonresponders. How these mutations affect the effectness of the therapy needs more information to Also, there were no significant differences in the numbers of mutation in ISDR between responders and nonresponders. This suggest the antiviral activity of the combination therapy is partly different from the interferon mono-therapy.