| 摘要: | 慢性B型肝炎病毒及C型肝炎病毒感染及其後遺症如肝硬化、肝細胞癌是一個嚴重的全球性問題，在台灣，15至20%之成年人是B型肝炎表面抗原 (hepatitis B surface antigen HBsAg) 的帶原者，而這些帶原者大部分有慢性肝炎，並每年分別以2%之發生率發生肝硬化及1%之發生率發生肝細胞癌。曾有研究指出在台灣有12.5%輸血者發生急性肝炎，其中60%轉變為慢性，而變為慢性的患者中85% C型肝炎抗體呈陽性。感染急性C型肝炎後，約有50%可發展為慢性C型肝炎。而約有10-20%最終發展為肝硬化，甚至導致肝癌。過去20年，很多抗病毒藥物、免疫調節藥或二者合併。曾經被試於臨床治療，在這些藥物中，對於慢性B型肝炎干擾素-a似乎有較好的療效，雖然30-40%成年白人患者經干擾素 -a治療後其Alanine aminotraansferase (ALT)恢復正常，HBeAg及HBV-DNA 轉陰，但其在亞洲地區療效並不理想。干擾素亦是目前治療慢性C型肝炎療效較佳的藥物，但使用時常引起輕度至中度全身副作用，且價格昂貴，干擾素-a雖然能降低血清HCV-RNA濃度及改善肝炎之血清生化指數，但50%在治療中肝功能恢復正常患者在減少劑量或停藥後六個月再度復發，最後僅15-25%之患者肝功能恢復正常且C型肝炎病毒清除，所以積極謀求治療B型及C型肝炎之道實為刻不容緩之事。 本研究擬評估常用於治療B型肝炎之中醫方劑逍遙散及逍遙散加味對慢性B型肝炎之臨床症狀、肝功能(Aspartate Transaminase:AST, Alanine Aminotransferase:ALT, bilirubin, Alkaline Phasphatase: Alk-P, g-glutamyl transferase:g-GT)，血清HBV-DNA，HBsAg與HBeAg之影響。並研究逍遙散及加味逍遙散B型肝炎病毒複製的抑制作用，測試有效的抑制B型肝炎病毒活性之藥物濃度及在較低濃度下可抑制B型肝炎病毒活性而不殺死細胞者。本計劃希望能以此去了解逍遙散、加味逍遙散及單味藥是否具細胞毒性, 是否能抑制細胞內病毒的複製、釋放及是否能提升免疫力以根除病毒。同時評估中醫臨床治療慢性C型肝炎有效治則-疏肝理氣、清熱解毒之常用方劑-四逆散及加味四逆散對慢性C型肝炎之臨床症狀，肝功能(AST，ALT，bilirubin、Alk-P，g-GT)與血清中HCV-RNA濃度之影響，並進一步評估四逆散及加味四逆散治療對C型肝炎病毒基因型之影響。並利用細胞分生的模式，進行四逆散、加味四逆散及組成成分根除C型肝炎病毒的體外療效評估。
Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection are a serious problem because of its worldwide distribution and possible adverse sequalae, such as cirrhosis and hepatocellular carcinoma .In southeast Asia, 15 to 20% of the population are hepatitis B surface antigen carriers, The majority of these carriers have chronic hepatitis and world progress to cirrhosis or hepatocellular carcinoma at the annual incidence of 2% and 1% respectively. There are 12.5% of patients who received blood transfusion developed acute post-transfusion hepatitis, in addition, 85% those patient HCV antibody positive. In the other hand, fifty percent of the acute hepatitis C patients developed to chronic hepatitis C and about 10-20% of them finally developed to liver cirrhosis or hepatoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among them, interferon alfa (IFN- a) has been shown to be effective, 30% to 40% of adult white patients with chronic hepatitis B lost hepatitis B e antigen (HBeAg) and HBV DNA when treated with IFN-a. However, the response rate is far from satisfactory, particularly in Asian patients, although corticosteroid priming may enhance the efficacy interferon therapy. Interferon-a (IFN-a) has been used for the treatment of chronic hepatitis C patients. Treatment of chronic hepatitis C with IFN-a decrease the serum HCV-RNA level, leading to improvement in serum biochemical parameters. However, about 50% of patients originally responding to interferon treatment relapsed within 6 months of either dose reduction or stopping interferon, only about one out of four patients is benefit from treatment sustained up to one year. There were many detail records about the mechanism, clinical symptoms and treatment of chronic hepatitis in traditional chinese medical books. In this research , we will evaluate the effect of Xiao-Yao-Sann and Xiao-Yao-Sann-Jia-Wei Commonly used to tre at chronic hepatitis B, on serum biochemical parameters、HBV-DNA、HBsAg and HBeAg in patients with chronic hepatitis B,and the inhibitory effect of Xiao-Yao-Sann、Xiao-Yao-Sann-Jia-Wei and its compoent on HBV in vitro. At the same time, the effects of Syh-Nih-Sann and Jia-Wei-Syh-Nih-Sann, which was used to treat chronic hepatitis C, to patients with chronic hepatitis C will be evaluated. Except the serum biochemical parameters, competative PCR will be performed to assess the change of viral load before and after teatment. In addition, to address whether different genotypes of HCV will influence the response rate or not, genotype of HCV will also be annalyzed in this study. We will also evaluate the inhibitory effect of Syh-Nih-Sann, Jia-Wei-Syh-Nih-Sann and it component on HCV in vitro. |
