2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649461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。肝細胞素(hepatokines)泛指肝臟組織所製造而分泌之血漿蛋白質，其中有幾種 已知與脂肪代謝、胰島素拮抗以及發炎反應有關。其中Hepassocin被發現在肝臟再生時表現 量增加，因而被認為可能急性肝衰竭時有助於肝臟再生。而學者也發現肝細胞癌的病人其 Hepassocin表現量下降，但是在非酒精性脂肪肝的病人血中Hepassocin的濃度卻遠高於正常 人，但目前並沒有針對Hepassocin與B型肝炎慢性感染及其往後產生肝硬化、肝癌的長期追 蹤研究。Fetuin-A已知與肝臟中葡萄糖與脂肪的代謝有關，並且在肝功能異常的狀況下濃度會 上升，進而產生脂肪肝。有一個歐洲的大型研究發現肝細胞癌的病人血中Fetuin-A的濃度有 顯著高於健康人。至於其他的肝細胞素，則尚未有人體上的研究報告，因此我們打算以縱斷式 的研究方法（longitudinal)以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B型肝 炎表面抗原（HBsAg)陽性且anti-HCV陰性者共3931人，使用其當初採集之血液檢體檢驗肝細 胞素來分析肝細胞素包括 Hepassocin、Fetuin-A、以及 sex hormone-binding globulin (SHBG) 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 increased 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. Our study also reveals that higher adiponectin is associated with higher risk of HCV related HCC, but there is no association between adiponectin levels and HCV RNA, indicating that some other mechanism may be involved in the carcinogenesis of adiponectin on HCV related HCC. 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.Hepatokines are defined as proteins exclusively or predominantly secreted from the liver and are known to directly affect glucose and lipid metabolism. Since hepatokines are primarily synthesized and secreted by the liver and have profound effects on whole-body metabolism, it is plausible that hepatokines may have significant effects on liver biology and diseases as well. We would like to evaluate the association between circulating hepatokines including hepassocin, fetuin-A and sex hormone-binding globulin (SHBG) levels and risk of HCC and HBV progression among subjects in REVEAL-HBV cohort in Taiwan. Since there is no study examining the relationshipbetween hepatokines and HCC risk among HBV carriers, in order to be efficient and save the cost and precious biosamples, we will use two-steps approach: First we will conduct a nested-case-control study within the REVEAL-HBV cohort to evaluate which hepatokines are associated with HCC risk among HBV carriers.Then we will carry out the test of the hepatokines that show association with HCC in the nested-case-control study on all the remaining HBV carriers in the entire cohort.