2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647711摘要：慢性C 型肝炎是一項重要的疾病，在台灣的盛行率約1-2%，而在蒙古有高達10％的盛行率。過去以長效型干擾素為主的治療，治療成效往往因為藥物的副作用而大打折扣，而近幾年出現的口服抗病毒藥物，則大大的提升病患接受藥物治療的意願及成功率。在治療病毒基因型1b 的眾多口服抗病毒藥中，由於daclatasvir (DCV) 合併 asunaprevir (ASV)的治療，價格只有其他藥物的一半，所以最有可能被用來作為第一線的治療。但這項藥物最大的缺點，在於若病毒已有NS5A 病毒抗藥株的突變，對於治療的效果，將從90％的成功率，降為40％。因此在這項計畫中，我們將發展NS5A 病毒抗藥株的定量檢測，來提升DCV 合併 ASV 的治療效果。以期利用最具經濟效益的方式，來治癒慢性C 型肝炎的患者。在第一年的計畫中，我們將先以發展NS5A 病毒抗藥株定量檢驗為主，同時將分析50 支慢性C型肝炎之病毒血清，探討這項檢驗的可靠性。在第二年的研究中，我們將分析NS5A 病毒抗藥株在100 位慢性C 型肝炎接受過干擾素治療患者出現的比例，並分析病毒抗藥株是否和疾病嚴重度有關，以及干擾素的治療是否會和NS5A 病毒抗藥株的突變有關，特別是干擾素治療失敗的患者，是否會容易產生NS5A 病毒抗藥株突變。在第3 年的計畫，我們將分析50 位慢性C 型肝炎接受DCV＋ASV 治療的患者，NS5A 病毒抗藥株的比例對於治療療效的影響。本研究為一個會回溯性、觀察性的研究，希望發展NS5A 病毒抗藥株定量方式，並探討NS5A 病毒抗藥株的定量，對於臨床及藥物療效的影響。<br> Abstract: Chronic infection of hepatitis C virus (HCV) is an important clinical issue, especially in Asia. Theprevalence rate is about 1-2% in Taiwan but higher than 10% in Mongolia, where are both dominantwith genotype 1b infection. Although there are oral anti-viral agents for HCV cure, the emergingquestion is how to provide a cost-effective treatment, which may facilitate the government to clear thevirus in the shortest period.In this proposal, we will focus on the detection and quantification of NS5A resistance-associatedvariant (RAV) of HCV, which is a key factor that lowers the response rate to daclatasvir (DCV) andasunaprevir (ASV), an all-oral regimen targeting HCV GT 1b. Since DCV+ASV is much cheaper thanother HCV regimens approved in Taiwan, patients without NS5A RAV can be regarded as thesuper-responders to the DCV+ASV regimen. Although Harvoni (a fixed dose combination ofsofosbuvir and ledipasvir) can achieve more than 95% of viral clearance rate and is available with alower price in Mongolia, patients who failed to clear the virus are also recommended to test NS5ARAV to guide the rescue therapy.In the first year of this proposal, we will develop a PCR-based assay to qualitatively determine whetherthe NS5A RAV exists in the HCV genome. With the qualitative data available, we will try to establish amore sensitive and accurate assay to quantify NS5A RAV with sensitivity of 5%. In the second year,we will explore the NS5A RAV prevalence in the serum of 100 HCV GT1b Taiwanese patients whohave received pegylated interferon treatment. For those who failed in pegylated interferon treatment, wewill analyze the serum after therapy. In the third year, we will explore the prevalence of HCV NS5ARAV in 50 Taiwanese patients who have already received DCV+ASV treatment, which may help usknow whether we could enhance DCV+ASV treatment response if excluding patients with NS5A RAVusing a more sensitive assay. In addition, we will also determine the NS5A RAV of Mongolian samples.The data will help the Mongolian patients to choose an appropriate therapy and the collaboration willhelp the Mongolian research group to develop their own viral research platform.In summary, we will explore HCV NS5A RAV in both Taiwanese and Mongolia HCV GT1b patients.This collaboration will not only help us confirm the robustness of our assay but also help the Mongoliagovernment know the prevalence of HCV NS5A RAV in HCV GT1b patients, which is important tocure HCV infection. Finally, the results of this proposal will facilitate both governments to eliminateHCV infection.