2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/650024摘要：C型肝炎被發現是目前已知的造成人類慢性感染的肝炎病毒中，與肥胖等有關的代謝因子有很強的相關，有些學者甚至認為C型肝炎也是代謝疾病的一種。流行病學研究發現C型肝炎帶原者普遍較非帶原者肥胖，有較高的糖尿病，比較差的血脂肪狀態，但到底是C型肝炎感染造成這些代謝疾病還是因為有這些不良代謝因子而造成較易感染C型肝炎則目前並無定論。除此之外，那些肥胖、有糖尿病及比較差的血脂肪狀態C型肝炎病人，其接受長效干擾素治療的效果也被發現較差。至目前為止，雖然探討代謝因子與C型肝炎的研究很多，但橫斷式且只有一個時間點的檢測值使得這些研究的結果仍然無法達成定論。脂肪激素(Adipocytokines)是一種脂肪組織所製造而分泌之血漿蛋白質。最近也有一些國內外的臨床研究觀察到血中脂肪激素的濃度與C型肝炎有關。也許脂肪激素在肥胖、糖尿病及高血脂與C型肝炎的感染狀態與疾病發展與治療效果上扮演著重要的角色，若能釐清此關係，或許可透過調節脂肪激素或藥物控制代謝疾病的方式而對C型肝炎的防治有所幫助。因此我們打算以縱斷式的研究方法(longitudinal)來分析脂肪激素的濃度及其他代謝因子之包括身體質量指數、腰圍、腰臀比、胰島素耐受性、總膽固醇、高密度及低密度膽固醇、三酸甘油酯在治療期間的變化與C型肝炎各種感染指標包括C型肝炎病毒指數、基因型以及治療之療效是否有相關。本計劃分兩部份進行，第一部分預計以由陳建仁教授主持的一個追蹤十年以上的由台灣北、中、南及澎湖離島居民所組成的世代(cohort)為基礎，選取此世代居民在初次進入研究時被檢驗出C型肝炎抗體陽性者共1095人，使用其當初採集之血液檢體檢驗脂肪激素包括adiponectin, leptin 以及visfatin，探討脂肪激素的濃度及其他代謝因子之包括身體質量指數、腰圍、腰臀比、總膽固醇、三酸甘油酯與C型肝炎各種感染指標包括C型肝炎病毒指數、基因型等是否有相關，此外，亦將研究脂肪激素的濃度及其他代謝因子是否影響其追蹤期間肝功能指數之變化與末期肝臟疾病如肝癌的發生以及是否死於肝硬化及肝臟相關疾病。第二部分預計與台大醫院劉振驊醫師合作，以劉醫師已收集完整臨床資料、血液及肝穿刺檢體的約1200名在台大醫院進行C型肝炎治療的病人為基礎，探討治療前、中、後脂肪激素的濃度及其他代謝因子之包括身體質量指數、腰圍、腰臀比、胰島素耐受性、總膽固醇、高密度及低密度膽固醇、三酸甘油酯與C型肝炎各種感染指標包括C型肝炎病毒指數、基因型在治療期間的變化以及治療之療效是否有相關。<br> Abstract: Chronic Hepatitis C infection is now considered one of the leading causes of liver relatedmorbidity and mortality, and poses significant threat to public health. It is estimated byWHO that more than 180 millions are chronically infected with this virus worldwide. InTaiwan, the prevalence of seropositive to antibody of HCV was estimated to be ranged from1-3% in general population, meaning around 300,000 to 600,000 patients. The mortalityrelated to HCV infection, including death from liver failure and hepatocellular carcinoma isexpected to continue to increase. The health issue related to chronic HCV infection isbecoming more and more important in Taiwan. Obesity, steatosis and insulin resistance (IR)are found to have a negative impact on CHC disease progression and the response to antiviraltherapy, and in turn, CHC is associated with alteration in glucose metabolism that leads tohepatic steatosis, IR and type 2 diabetes mellitus. Hepatitis C infection is now considered asystemic disease that involves lipid metabolism and several metabolic related factors arefound to be related to HCV infection and disease progression. Over the last 10 years, atremendous increase in our knowledge of the relations between factors produced by theadipose tissue and pathophysiology of the hepatic disease because of the central role of theliver in the metabolic syndrome. However, the results are still inconsistent and controversialwhen studying human subjects due to their inherent complexity. We propose to conduct twoparts of study in hope for helping providing further evidence: first part is a community-basedcohort follow-up study to investigate whether the metabolic factors and serum adipocytokineslevels at baseline influence the hepatitis C infection status and disease progression amongresidents with chronic hepatitis C (CHC) without treatment. The second part is ahospital-based longitudinal study by using a set of CHC patients who underwent Peg-IFN andribavirin treatment at NTUH and whose metabolic factors at pretreatment, end of treatmentand 6 months after treatment stages were already collected. We will further test the serumadipocytokines levels at this three time points and perform a longitudinal data analysis thattakes into account repeated data measurements to determine whether the changes or the trendsof these metabolics predicts their treatment outcome.