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研究生:黃昭敏
研究生(外文):Chao-Min Huang
論文名稱:分子生物標誌在慢性病毒肝炎之預測指標相關性研究
論文名稱(外文):A study of molecular biomarkers for therapeutic outcome in chronic viral hepatitis
指導教授:胡琮輝
指導教授(外文):Tsung-Hui Hu
學位類別:博士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2017
畢業學年度:106
語文別:中文
論文頁數:98
中文關鍵詞:長效型干擾素持續性病毒學反應單一核苷酸多型性肝脂肪變性C型肝炎病毒肝硬化肝癌
外文關鍵詞:Hepatitis C virus (HCV)CirrhosisHepatocellular carcinoma (HCC)Pegylated interferon (peg-IFN)hepatic steatosis (HS)Sustained virological response (SVR)Single nucleotide polymorphisms (SNPs)
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感染B或C型肝炎病毒會成為慢性肝炎,也是導致肝硬化和肝癌的最主要原因。在台灣引起國人慢性肝病甚至肝癌最主要的原因就是B、C型肝炎病毒感染,慢性B型肝炎感染主要是在生產時母親傳給嬰幼兒,傳染率高達90%以上,民國73年在政府努力推動實施新生兒B型肝炎疫苗接種與慢性B型肝炎追蹤治療後,民眾因B型肝炎引發肝癌的致死率已有逐年下降,但因C型肝炎引發肝癌的致死率卻連年攀升,感染C型肝炎病毒有70~80%的人會成為慢性感染,且隨著時間的進展,慢性C型肝炎可能進展至肝纖維化、肝硬化、肝衰竭或肝癌而導致死亡。因此能有效治療慢性C型肝炎,使患者之血清中C型肝炎病毒完全消失,達到持續病毒學反應(SVR)是重要目標。臨床上慢性C型肝炎之標準治療方式為每週施打一次長效型干擾素(peg-IFN),合併使用每日口服雷巴威林(ribavirine),但由於藥物的許多副作用,並非每個病人皆可完成治療,因此早期的診斷或預測療效,是臨床上非常重要的指標。研究抗病毒治療成功與否主要與病毒因素(基因型、病毒量、病毒變異)和宿主因素(種族、年齡,胰島素抗阻和單一核苷酸多型性)有關,其中利用全基因體相關研究(GWAS),發現在IL28B附近的單一核苷酸多型性(SNPs)與抗病毒治療療效有密切關聯,因此我們將針對IL28B的單一核苷酸多型性與干擾素治療後發生肝癌之危險因子加以研究。
在慢性C型肝炎患者也很常見有肝脂肪變性,並且加速肝纖維化的產生,目前已知有許多相關遺傳因子與肝脂肪變性產生有關,最常見的是PNPLA3基因上的rs738409基因單一核苷酸多型性,因此我們也將PNPLA3與IL28基因的單一核苷酸多型性在慢性C型肝炎與肝脂肪變性患者之間的關聯性加以研究。
A major cause of chronic hepatitis is infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and also a risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). In Taiwan the major transmission of HBV is from mother to child during childbirth (more than 90%). Since vaccines for the prevention of hepatitis B have been routinely recommended for babies, the common cause of cancer-related death with HBV have decrease, but with hepatitis C have increase. Chronic hepatitis C is often asymptomatic, but may slowly progress to liver fibrosis, decompensated cirrhosis, hepatocellular carcinoma and terminating to death. Therefore, it has been assumed that eradication of HCV which achieve sustained virological response (SVR) would provide the most effective means of preventing HCC. Currently, pegylated interferon (peg-IFN) combination with ribavirine (RBV) represents the mainstay of treatment for chronic hepatitis C. Genome-wide association studies (GWAS) reported single nucleotide polymorphisms (SNPs) near the IL28B locus that displayed association with treatment response. We investigated in patients with chronic HCV infection showing the risk factors and tried to increase our understanding of the predictive ability of IL28B for HCC development in HCV chronic infection treated with peg-IFN/RBV.
Hepatic steatosis (HS) is common in patients infected with HCV and appears to be associated with a more rapid progression of liver fibrosis. Several genetic risk factors for HS have been identified, the best documented one being a SNP in rs738409 in the PNPLA3 gene. We were study in the association of PNPLA3 and IL28B polymorphism with HS in chronic hepatitis C patients.
論文審定書 …………………………………………………………………………i
誌謝 …………………………………………………………………………………ii
中文摘要 ……………………………………………………………………………iii
英文摘要 ……………………………………………………………………………iv
目錄 …………………………………………………………………………………v
圖次 …………………………………………………………………………………vi
表次 …………………………………………………………………………………vii
第一章 緒論 ………………………………………………………………………1
第一節 前言 ……………………………………………………………………..1
第二節 B型肝炎病毒(Hepatitis B virus, HBV)介紹 ……………..……………2
第三節 C型肝炎病毒(Hepatitis C virus, HBV)介紹 …………………..………11
第四節 單核苷酸多型性(single nucleotide polymorphisms: SNP) ……….……25
第五節 肝脂肪變性/脂肪肝(Hepatic steatosis/Fatty liver) ……………………26
第二章 材料與方法 ……………………………………………………….……28
第一節 病人檢體收集 …………………………………………………….……28
第二節 B型肝炎病毒相關檢測 ………………………………………………28
第三節 C型肝炎病毒相關檢測 ………………………………………………30
第四節 DNA核酸萃取與單一核苷酸基因分型(SNP) ….……………………33
第五節 數據統計分析 .……….………………………………………………34
第三章 結果分析 ………………………………………………………………35
第一節 慢性B型肝炎與嚴重肝病的相關因子 ……………………………35
第二節 慢性C型肝炎病人有效治療因子預測與肝癌產生的相關性 ……37
第三節 慢性C型肝炎病人的單基因多型性與肝脂肪變性的關係 ………41
第四章 討論 ……………………………………………………………………43
第一節 慢性B型肝炎與嚴重肝病的相關因子 ……………………………43
第二節 慢性C型肝炎病人有效治療因子預測與肝癌產生的相關性 ……44
第三節 慢性C型肝炎病人的單基因多型性與肝脂肪變性的關係 ………46
第五章 未來發展 ………………………………………………………………48
參考文獻 …………………………………………………………………………79
論文著作及發表 …………………………………………………………………88
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