慢性C型肝炎病患之代謝異常

Metabolic Disorders in Patients with Chronic Hepatitis C Virus Infection

黃志富(Jee-Fu Huang)

指導教授 ： 莊萬龍

高雄醫學大學/醫學院/醫學研究所/博士(2011年)

https://doi.org/10.6832/KMU.2011.00073

摘要

病毒性肝炎及其衍生之慢性肝炎、肝硬化及肝癌對國人的健康一直是相當大的威脅。雖然B型肝炎對國人健康的威脅將會因國內B型肝炎疫苗的全面性推廣而降低，但C型肝炎感染導致之高慢性帶病率將演變成我國最主要之肝病問題。雖然國內一般人口的C型肝炎帶原率低於5%，但南部地區的帶原率約為8-10%，某些高盛行鄉鎮其帶原率甚至可高達30-40%。是以C型肝炎病毒的感染在目前與可見之未來將是我國引起慢性肝病、肝硬化及肝細胞癌重要的原因，對國人的健康威脅預期將會越來越巨大，因此對慢性C型肝炎感染的相關研究更顯重要與迫切。
C型肝炎病毒不僅是一親肝性病毒，亦是一種親淋巴性病毒，不僅會對肝細胞造成程度不一的損害，也會對肝臟以外的其他組織造成影響或損傷，進而表現出所謂的肝外表徵。這些肝外表徵大多由C型肝炎病毒引發之自體免疫反應或自體免疫相關疾病而導致。分子或抗原的相似性、宿主對疾病的耐受敏感性，以及免疫反應的調節異常亦可能扮演重要角色。以往的研究顯示慢性C型肝炎感染重要的肝外表徵主要為代謝異常例如糖尿病、甲狀腺自體抗體的產生與功能異常、腎絲球病變、混合型冷凝血症、及其他自體免疫疾病。我國以往有關於慢性C型肝炎感染相關代謝異常的研究稍嫌零星、不夠完整，而且在慢性病毒性肝炎盛行的我國其相關研究尚屬起步階段。
因此學生先由流行病學的角度切入探討慢性C型肝炎感染衍生之代謝異常疾患，包括蛋白尿、第二型糖尿病、代謝症候群等的盛行率及相關因子。其次再由臨床分子生物學及病毒學等面向，以進一步探討慢性C型肝炎病患其葡萄糖代謝異常與胰島素阻抗性之臨床特徵與抗病毒藥物治療效果之關聯與影響。近年來對於慢性C型肝炎的診斷特別是與其相關之生物標記研究進展日新月異，是以學生亦由轉譯醫學的角度對於慢性C型肝炎病患上述的代謝異常與目前被廣泛研究之細胞激素其相關因素做臨床上組織病理學、分子生物學與病毒學學觀察分析，以探討可能之作用機制與病理機轉。

關鍵字

C型肝炎病毒 ； 代謝症候群

並列摘要

Viral hepatitis infection and its related chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma remain a tremendous concern of public health in Taiwan at present. The prevalence of hepatitis B virus (HBV) infection and its leading liver diseases will be decreased and diminished in the foreseeable future post the era of our nation-wide launch of HBV vaccination in 1984. However, the multi-directional issues of hepatitis C virus (HCV) infection have come up progressively for the past 1-2 decades. It is well known that 70-80% of the individuals will become a chronic state after an acute HCV infection. Moreover, 20-30% of the chronic HCV infection (CHC) patients will progress to liver cirrhosis after an estimated period of 20-30 years, and a proportion of them will face the threaten of hepatocellular carcinoma. The prevalence of HCV infection in general populations was reported to be <5% in our country. Nonetheless, the prevalence of HCV infection in some townships of southern Taiwan reached as high as 30-40%. Therefore, there is a pressing need to clarify the associated covariates between HCV infection and its related disorders.
HCV per se is both hepatotropic and lymphotropic. Replication of HCV in diseased extrahepatic organs and tissues may have cytopathic effects. It, therefore, may either trigger latent autoimmunity or induce an autoimmune disease de novo. Molecular mimicry, unfolded protein response and/or immunological dysregulation may contribute to possible pathogenetic mechanisms. Therefore, in addition to established liver injury, there are multiple examples of extrahepatic metabolic disorders attributed to HCV infection, such as type 2 diabetes mellitus (T2DM), thyroiditis, glomerulopathy, mixed cryoglobulinemia, and other immunological abnormalities. Previous reports or studies concerning metabolic abnormalities of CHC were scattered and not fully integrated. Moreover, there were only few studies addressing these issues in the past decade in Taiwan, an endemic country of viral hepatitis.
The aims of my serial studies initially focused on the metabolic manifestations of CHC, e.g. proteinuria and its related renal disorders, T2DM and metabolic syndrome to elucidate the characteristics of metabolic abnormalities and their clinical relevants from the aspect of epidemiological view. Native related database has thus been established with collaborative works from my distinguished colleagues.
Secondly, related studies have been conducting to investigate the interaction between glucose abnormalities and CHC, particularly in the aspects of molecular biology, virology and clinical therapeutics. I also tried to clarify the mutual roles of insulin resistance and CHC with respect to the prediction of treatment efficacy, how treatment response affects insulin resistance and the role of pancreatic beta cell function in the interesting suite.
Recently, the studies regarding cytokines prevail worldwide. With the help and kind instruction from my colleagues and tutors, I conducted several translational studies aiming to elucidate the specific roles of the newcomers in a clinical setting. It will be helpful to clarify the host viral interaction and possible pathogenetic mechanisms of this topic.

並列關鍵字

hepatitis C virus (HCV) ； metabolic syndrome

參考文獻

References

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