于明暉臺灣大學:流行病學研究所趙俐婷Chao, Li-TingLi-TingChao2010-05-052018-06-292010-05-052018-06-292009U0001-1607200918274900http://ntur.lib.ntu.edu.tw//handle/246246/180807背景：非酒精脂肪肝疾病被發現與許多代謝因子有關。最近的動物實驗也發現B型肝炎病毒X蛋白質的表現會直接影響脂肪在肝臟聚集。本研究應用病例世代研究設計評估病毒和代謝因子對於B型肝炎自然史的影響，特別強調血糖、胰島素和胰島素阻抗的作用。料與方法：研究世代為1989年8月至1992年6月在公保健診中心接受健康檢查的B型肝炎男性帶原者且年齡在30歲以上，共計2903人參與，追蹤16年。本研究依據病例世代研究設計，從中隨機選取1143名個案作為研究樣本，追蹤至2005年，共診斷出118名HCC新發病例。HBV genotype和HBV DNA濃度的長期變化是以PCR-based進行測量，並採用非條件式邏輯斯迴歸評估代謝因子、病毒因子與HCC發生之相關性。果：在控制年齡、抽菸、喝酒習慣、糖尿病及身體質量指數後，胰島素(P=0.0016)及胰島素阻抗(P= 0.0226)與HCC的發生有關，危險性呈現J型分佈。另外，本研究也發現胰島素、和病毒量對於追蹤期間GGT的提高具有累加性的交互作用，在HBV DNA濃度≥ 5.91 log copies/mL，且存在高濃度胰島素或胰島素阻抗者，追蹤期間至少一次GGT提高的危險性最高。然而，本研究未發現基線血糖值與罹患HCC之相關性。論：胰島素、胰島素阻抗、HBV病毒量和NAFLD相關的病理變化導致的HCC有關。Background: Nonalcoholic fatty liver disease is strongly associated with metabolic syndrome. In a recent animal model, increased expression of the hepatitis B virus (HBV) X protein can induce the accumulation of lipid in hepatocytes. By applying a case-cohort study, we aimed to evaluate the effects of both metabolic and viral factors on the development of hepatocellular carcinoma (HCC) among HBV carriers. aterials & Methods: Study subjects included a total of 1143 male HBV carriers (of whom 118 incident HCC cases were identified during follow-up) ages ≥30 years sampled from a cohort (1989-1992) of 2903 government employees who had been followed for 16 years. HBV genotype and prediagnostic viral load at multiple time points were measured by PCR-based methods. Unconditional logistic regression was used to determine the associations between metabolic and viral factors and HCC.esult: After adjusting for age at entry, cigarette smoking, alcohol consumption, diabetes and body mass index, baseline plasma concentrations of insulin (P=0.0016) and insulin resistance (P= 0.0226) were associated with progression from healthy HBV carrier state to HCC. The risk of incident HCC had a J-shaped association with the insulin concentrations, regardless of diabetes mellitus history. There were additive associations of viral load and higher insulin concentrations with HCC, such that the highest risk of HCC was found among individuals with both a high viral load of >5.91 copies/mL and a high insulin concentration or a high value of insulin resistance. However, we failed to find an association between baseline glucose levels in blood and HCC. onclusions: Prediagnostic plasma insulin, insulin resistance, and HBV DNA levels predict the risk of developing HCC.中文摘要 ii文摘要 iii究背景 1料與方法 6果 10論 14考文獻 20application/pdf350001 bytesapplication/pdfen-US胰島素血糖B型肝炎病毒肝細胞癌世代研究Insulinglucosehepatitis B virushepatocellular carcinomacohort[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/180807/1/ntu-98-R96842017-1.pdf