2013-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649734摘要：慢性肝炎所造成危害國民健康眾所皆知，B型肝炎病毒（Hepatitis B virus，HBV）感染是全球性的公共衛生問題，估計全世界有超過 20億人（約全球三分之一人口）曾經感染過 B型肝炎病毒，其中 B型肝炎表面抗原（HBsAg）帶原者約有 3.5億人口，尤其以亞太地區及撒哈拉沙漠以南非洲地區特別盛行，台灣亦為 B型肝炎感染之高盛行區，一般族群成年人的慢性 HBsAg帶原率為 15%至 20%。台灣地區之慢性肝炎主要經由肝炎病毒感染所造成。過去研究已知台灣病毒性肝炎之主要致病原為 B型肝炎病毒。慢性肝炎病毒感染是造成肝癌的一個很重要因素之一。脂肪激素(Adipocytokines)是一種脂肪組織所製造而分泌之血漿蛋白質。脂締素(Adiponectin)是一種脂肪組織所製造而分泌之血漿蛋白質。最近的國內外的臨床研究也觀察到血中脂締素的濃度較低的人似乎各種癌症包括結直腸癌、乳癌、子宮內膜癌、胃癌等的發生機率顯著的升高。因此我們以前瞻式的方式，從一個已經被追蹤將近十年的社區世代中以聯結至全國癌症登記檔的方式，找出此一世代中所有在追蹤期間新發生的肝癌病人，並以配對年齡、性別、以及居住地的方式，從其他健康的世代成員中以 1:2的比例隨機選出健康對照，再以其剛進入世代時所被採集的血液檢體測量脂締素的濃度，結果顯示高年齡、女性、以及肝癌病人其血液中的脂缔素濃度較高，而抽菸、較肥胖、有糖尿病史以及有非酒精性脂肪肝史的人，則血中脂缔素濃度較低。脂缔素濃度愈高的人其產生肝癌的風險也愈高，並且有顯著的劑量效應。因為有此發現，我們接著想要探討代謝因子與 B型肝炎感染狀態是否也有相關，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。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變化，再加上其他代謝因子包括身體質量指數、腰圍、腰臀比、總膽固醇、三酸甘油酯與脂缔素濃度是否與 B型肝炎各種感染指標有關，包括 B型肝炎病毒指數、基因型、肝功能指數之變化、B型肝炎病毒指數之變化，是否在追蹤期間達到B型肝炎表面抗原、B型肝炎 e抗原、B型肝炎病毒指數的清除以及相關抗體的產生，最後並探討與末期肝臟疾病如肝硬化、肝癌的發生以及是否死於肝硬化及肝臟相關疾病的關係。<br> Abstract: In Taiwan, approximately 8000 were newly diagnosed with liver cancer annually, and it was ranked first in cancer incidence and mortality in men. Metabolic factors, especially obesity and diabetes were found to be associated with an increase risk of hepatocellular carcinoma (HCC) in epidemiological studies. Our previous study showed that metabolic factors, especially obesity and diabetes mellitus (DM) are associated with increased risk of primary liver cancer differently depending on HBV and HCV infections1. The exact mechanism of this relationship remains unknown, but recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of several cancer sites including liver. Taiwan is among one of the most endemic areas with the estimation of about 3 million chronic HBV carriers (15-20%) in the 1970’s. The mass vaccination of hepatitis B has substantially reduced the mortality and morbidity of liver disease related to chronic HBV infection in Taiwan. In our following nested-case-control study, we found that elevated plasma adiponectin levels was independently associated with increased HCC risk, and the risk was higher among those with HBV infection characteristics that were related to worse prognosis. The findings of metabolic factors are related to metabolic related or virus induced liver diseases risk differently may shed some light in understanding the pathogenesis of liver diseases. With increasing prevalence of obesity and diabetes in Taiwan, it is important to elucidate the complex relationship between metabolic factors and risk of all spectrums of liver diseases including hepatitis B, hepatitis C, liver cirrhosis, HCC and liver related mortality. The metabolic factors we investigated included obesity, diabetes, lipid profile and plasma adiponectin levels. We propose to conduct tests of plasma adiponectin levels at baseline and during follow-up on all HBsAg seropositive participants of a community-based cohort that included residents in seven townships in Taiwan to investigate prospectively and longitudinally the association between circulating adiponectin levels and other metabolic factors including obesity, diabetes, hypertension, hyperlipidemia and risk of parameters and progression of HBV infections.代謝因子 脂締素 B型肝炎 肝硬化 肝癌