干扰素-α治疗慢性乙型肝炎的机制、疗效及其影响因素的研究进展  

The mechanism, efficacy and influencing factor of interferon-α therapy in chronic hepatitis B

作　　者：杨灏[1] 周钢桥[1] 贺福初[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《国际流行病学传染病学杂志》2006年第4期247-250,254,共5页International Journal of Epidemiology and Infectious Disease

基　　金：中国高技术研究发展计划(2001AA224011);科技专项计划(2002BA711A10);军队医药卫生科研基金(01Z018);国家自然科学基金委创新研究群体科学基金(30321003)。

摘　　要：干扰素(IFN)_α是目前治疗慢性乙型肝炎(CHB)的主要药物之一,具有广谱抗病毒和免疫调节两方面的作用,可抑制病毒DNA复制和RNA合成,促进病毒RNA降解,抑制病毒蛋白的合成和转运及病毒颗粒的成熟和分泌,能促进人类白细胞抗原Ⅰ、Ⅱ类分子的表达及增强CTL、APC和NK细胞等的活性。及时应用IFN_α治疗,对于机体阻断HBV感染的慢性化以及随后的病程进展具有积极的疗效,且用改良后的新一代聚乙二醇_IFN_α(PEG_IFN_α)治疗CHB患者,取得了更加不错的疗效。然而,IFN_α有较严格的适应征,其治疗CHB的总有效率至今不超过40%。许多研究表明,HBV的基因型、特定的环境因素和人体的遗传因素是影响IFN_α疗效的主要因素。要提高IFN_α的治疗效果,就必须对以上各影响因素的分子机制进行研究,以改善疗效,指导未来临床合理化或个体化用药。In the past two decades, interferon-α （IFN-α） has been proven effective in the treatment of chronic hepatitis B patients. Many IFN-inducible proteins within single cells have the antiviral fimction, which inhibit DNA replication, RNA synthesis and translation and viral nucleocapsids transport. Also IFN-α induced expression of HLA class Ⅰ and class Ⅱ antigens and IFN-γ may contribute to the antiviral responses within whole body, which enhance the fimction of cytotoxic T lymphocyte （CTL）, antigen presenting cell（APC）, natural killer cell （NK cell） and other immunocytes. Four to six months of IFN-α therapy resulted in HBeAg loss in approximately 33% of HBeAg-positive patients. While HBeAg-negative patients need longer duration of treatment （10% - 15% sustained response with 4/6 months treatment： approximately 30% sustained response with 12/24 months treatment）. Recently, Pegylation （PEG）-IFN-α, an improved IFN-α, was shown to be superior to conventional IFN-α in HBeAg-positive disease and to lamivudine in both HBeAg-positive and HBeAg-negative chronic hepatitis B. Further more, the side effect of PEG-IFN-α was reasonable, h could become the better choice in many patients with both HBeAg-positive and HBeAg-negative disease. However, only one third of patients achieve a durable response to a course of IFN therapy. The influencing factor of nonresponse include immunotolerance, HBV DNA genotype and human genetic background. First, predictors of immunotolerance include normal serum ALT levels, high serum HBV DNA levels, and childhood infection, which mean a lower frequency of sustained respouse of IFN. Second, many studies showed that HBV genotype A and B, compared to genotype C and D, is associated with a higher frequency of seroconversion in HBeAg-positive patients. Third, some studies showed that MHC class Ⅱ gene and eukaryote initiation factor-2α （eIF-2α） gene polymorphisms were associated with the frequency of sustained responder. In conclusion, IFN-α, an immunomodulan

关 键 词：干扰素-Α 乙型肝炎病毒 慢性乙型肝炎 

分 类 号：R512.62[医药卫生—内科学] R644[医药卫生—临床医学]