2017-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648967摘要：B 型肝炎病毒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 型肝炎表面抗原帶原者約有3.5 億人，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，台灣一般成年人的慢性HBsAg 帶原率為15%至20%。慢性B 型肝炎病毒感染之後遺症如肝硬化和肝細胞癌仍舊是國人健康的大敵。在自然病程中約30-40%帶原者會演變成慢性肝炎，每年約2%慢性B 型肝炎患者會演變成肝硬化，每年約3-10%肝硬化患者會得到肝細胞癌。B 型肝炎病毒感染的自然史，從無症狀感染、慢性肝炎、進展成末期肝臟疾病，存在很明顯的個體差異，而造成這些差異的原因正被逐步的探討闡明。核糖核酸脢-L(Ribonuclease L, RNase L)是RNA 病毒感染後所誘發的先天性免疫機制中的蛋白之一，並與許多具有抗病毒能力的前驅發炎因子生成有緊密關聯。而除了發炎與新陳代謝有直接相關外，RNase L 的免疫角色是否能夠衍伸至受到B 型肝炎病毒感染的病患的病情進展問題，尤其是發展到末期肝臟疾病包括肝硬化與肝癌，是一個值得探討的課題。本研究將分成三個階段來探討RNase L 血清內蛋白量與B 型肝炎感染及其進展的相關性。第一階段是以台大醫院肝炎中心收集的5 種臨床上所代表不同感染階段的B 型肝炎病人，包括inactivecarriers, active carriers with low HBV viral load, active carriers with high HBV viral load,肝硬化以及肝癌各300 名，測量其血清中RNase L 蛋白量，以了解RNase L 蛋白量是否與B 型肝炎感染進程有相關。 第二階段是以台大醫院肝炎中心收集追蹤的B 型肝炎病人，以nested case-controlstudy 的方式選取出追蹤期間新罹患的肝癌病人，並以配對的方式在沒有產生肝癌的病人中選取出對照組，以這些人發病前(病例組)或第一次抽取(對照組)的血清，測量其血清中RNase L 蛋白量以及與RNase L 調控有關的基因多型性，以了解RNase L 蛋白量是否與B 型肝炎造成的肝癌有關。第三階段是以在台大醫院肝炎中心接受過干擾素治療的B 型肝炎病人，並已接受口服抗病毒藥的病人為對照組，測量治療前後血清中RNase L 蛋白量，以探討是否血清中RNase L 蛋白量可以成為B 型肝炎干擾素治療的成功與否的預測因子。<br> Abstract: Hepatitis B virus (HBV) infection poses a serious public health threat in the world, especially in theendemic areas (defined by prevalence >8%) including Southeast Asia and Sub-Saharan Africa that takes upabout 75% of the cases. These chronic HBV carriers are at much higher risk of developing cirrhosis, hepaticdecompensation, hepatocellular carcinoma, and even liver related causes of deaths. Hepatitis B infectionsaccount for more than 600,000 deaths from decompensated cirrhosis or hepatocellular carcinoma each year.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.Messenger RNA (mRNA) plays a critical role in maintaining cellular functions and homeostasis.Aberrant regulation of mRNA stability is involved in the pathogenesis of metabolic disorders, immunedysfunction and cancers. Ribonuclease L (RNase L) was demonstrated to degrade various specificendogenous mRNAs, hence capable of regulating several cellular functions, including development, cellcycle and even tumorigenesis. The main study population will be from patients recruited in the Elucidationof Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers (ERADICATE-B)study. These patients were enrolled from 1985 to 2000 at the National Taiwan University Hospital. In total,3947 HBsAg-positive patients aged older than 28 years were consecutively enrolled between 1985 and 2000.All of them had been HBsAg-positive for longer than 6 months and received more than 3 years of regularfollow-up at the National Taiwan University Hospital. Since there is no study examining the relationshipbetween RNase L and hepatitis B infection in human, in order to be efficient and save the cost and preciousbiosamples, we would like to propose the current study with following three-phase approach: First we willconduct a cross-sectional study to investigate the relationship between serum RNase-L levels and differentstage of HBV infection including inactive carriers, active carriers with low viral load, active carriers withhigh viral load, liver cirrhosis and hepatocellular carcinoma (HCC). Then we will conduct anested-case-control study within the cohort to evaluate whether serum RNase L levels and the geneticpolymorphism of RNase L is associated with HCC risk among HBV carriers. In the last phase, we willlongitudinally examine serum RNase L levels before and after short term and long term interferon treatmentfor HBV infection using patients undertaken HBV nucleos(t)ide analogue (NUC) therapy as comparisongroup, to elucidate whether RNase L can predict HBV interferon treatment effect.