越來越多的證據顯示甲型干擾素(Interferon-)與ribavirin的合併使用，對C型肝炎病毒的治療有顯著效用，除了已知由病毒造成的原因之外，藥物在免疫反應方面的調控作用，也使得某些與調控免疫反應有關的蛋白表現受影響，進而影響了治療的療效。例如CD81這個廣泛表現在免疫細胞(如B細胞, T細胞，及NK細胞)上並影響著免疫反應辨認及調節的分子，由於會與C型肝炎病毒的E2蛋白結合而被認為可能與病毒逃避免疫反應的攻擊有關。在此研究中我們偵測健康人及未用藥C型肝炎患者之周邊血液單核細胞上CD81的表現，以及此蛋白在健康人、未用藥C型肝炎患者、接受過干擾素治療之治癒者及未治癒者之周邊血液單核細胞上，CD81受到甲型干擾素調控後的表現情況，結果顯示C感染型肝炎病毒並不會影響此蛋白在B細胞, T細胞，及NK細胞上的表現及受到甲型干擾素調控的能力，然而CD81受到甲型干擾素調控的程度卻在接受過干擾素治療之治癒者及未治癒者之周邊血液單核細胞上出現差異，在治癒者的B細胞上CD81的表現會受到顯著的調降，而在未治癒者的細胞上則不會有這樣的現象，我們進一步的研究此調控的分子機轉，發現甲型干擾素只會調降CD81的蛋白而不會調降RNA表現；而這樣的調降作用在合併處理雙鏈RNA活化酵素的抑制劑-2-aminopurine，後會被抑制，顯示此作用可能經由雙鏈RNA活化酵素來執行。在C型肝炎治療中，我們還利用縱向研究探討細胞表面蛋白受甲型干擾素調控情況與治療療效的關係，初步結果指出CD81在各種周邊血液單核細胞上的調控表現皆與病毒的清除無關，然而病毒清除卻與HLA-ABC分子在B細胞及單核球細胞上受到調升呈現顯著相關。綜合我們的結果，顯示C型肝炎病毒感染並不會影響CD81在周邊血液單核球上的表現及其受甲型干擾素的調控能力，而甲型干擾素在B細胞上對CD81的調控表現或許可做為治療結果的指標，由初步的縱向性研究結果，顯示在C型肝炎的治療中Th1免疫反應的調升可能與病毒清除呈現顯著相關性。

　　Available evidence demonstrated that interferon-alpha (IFN-) along with ribavirin exerted apparent therapeutic effect on clearance of hepatitis C virus. Beside virological factors, host factors, such as certain immunological regulators, seem to affect the outcome of antiviral treatment of IFN- and ribavirin since both agents have shown immunomodulation. Among these, human CD81, a HCV E2 binding protein, might participate in HCV escaping mechanism from host immune surveillance. Surface CD81 molecule accounts for the recognition of immune response which is broadly coordinated between many cell types, such as B, T, natural killer (NK) and other stromal cells. In this study, CD81 expression was assessed on the surface of fresh-isolated peripheral blood mononuclear cells (PBMC) from healthy donors and naïve HCV patients and the surface of IFN--cultivated PBMCs from healthy donors, naïve HCV patients, and responders and non-responders of combination therapy. Data showed that no difference of CD81 expression on T, B and NK cells existed between healthy subjects and patients with HCV infection. There was no difference of IFN--induced CD81 down-regulation between healthy donors and naïve patients. However, treatment of IFN- significantly decreased CD81 expression on B cells in PBMC from patients with sustained virological response, but not those without it. For the molecular mechanisms, we showed that IFN-treatment reduced the surface CD81 protein, but not the CD81 RNA. The IFN- function could be restored by 2-aminopurine, suggesting double-stranded RNA activated kinase (PKR) were involved. The relevance of therapeutic responses with IFN--induced surface-protein modulation was also examined in a longitudinal study. CD81 expression on subpopulations of PBMCs was not significantly different between virological responders and non-responders. However, preliminary results from longitudinal investigation showed that the expression of HLA-ABC molecules was significantly up-regulated on B cells and monocytes from virological responders, but not from non-responders. In conclusion, our data suggested the modulation effect of IFN- on CD81 expression is not related to HCV infection. The alteration of expression of surface CD81 on B cells might be an indicator for the outcome of IFN- treatment. Results from longitudinal study might suggest that Th1 responses could be augmented during IFN- treatment in the virological responders in HCV infection.

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