| Summary: | 碩士 === 中山醫學大學 === 生物化學研究所 === 90 === Chronic Hepatitis C infection has been an important health topic in Taiwan since no effective and protective vaccines available for prophylaxis and then treatment becomes the practicable way for blocking the disease progression to hepatoma or cirrhosis. The interaction between Interferon Sensitivity Determine Region (ISDR) of Non-structural 5A (NS5A) of HCV and protein kinase R (PKR), an interferon-responsive protein has been reported and therefore, it was speculated that mutations within the ISDR region may interfere the efficiency of interferon therapy. This hypothesis has been verified by several studies; however, conflicting results were also presented. In this study, 70 patients with chronic HCV infection, 52 patients were infected with genotype 1b and the other 18 patients were infected with mixed genotypes (1a+1b or 1b+2a), who have undergone the interferon-ribavirin therapy were recruited for evaluating the influences of various host and viral factors on the treatment efficiency. Before the treatment, serum samples were collected from every patient for routine laboratory tests and viral sequence analysis. As the results shown, certain host factors, including ALT, BUN and TBIL, have relationships, although not statistically significant, to the treatment efficiency insignificant while mutation of ISDR region has no impact on the treatment efficiency although several mutations, including serine to praline at 2210, histidine to arginine at 2218, histidine to arginine at 2219, aspartic acid to arginine at 2223, alanine to serine at 2224, and isioleucine to phylalanine at 2227. In addition, 7 missense mutations of nucleotides, including T6971C, T6996C, C7036T, G7059A, C7068T, T7076C and A9081G, were identified in all isolates which may present local variations. The impact of these variations and mutations on the binding activity of resulting NS5A proteins to PKR warrants further investigation.
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