1、乙型病毒性肝炎,慢性乙肝防治,慢性乙型肝炎治疗的总体目标是：最大限度地长期抑制或消除HBV，减轻肝细胞炎症坏死及肝纤维化，延缓和阻止疾病进展，减少和防止肝脏失代偿、肝硬化、HCC 及其并发症的发生，从而改善生活质量和延长存活时间。 慢性乙型肝炎治疗主要包括抗病毒、免疫调节、抗炎保肝、抗纤维化和对症治疗，其中抗病毒治疗是关键，只要有适应证，且条件允许，就应进行规范的抗病毒治疗。,干扰素治疗,干扰素阻断病毒繁殖和复制，但不能进入宿主细胞直接杀灭病毒，而是与细胞膜接触并在细胞内产生一种特殊蛋白质即抗病毒蛋白，后者可抑制病毒mRNA信息的传递，从而阻止病毒在宿主细胞内繁殖。 干扰素在病毒感染的细胞中还
2、能诱导蛋白激酶及25寡腺苷合成酶的产生，然后激活一个内源性核酸内切酶降解病毒RNA，同时蛋白激酶能灭活核糖体合成所必需的酶，从而使蛋白合成减少，病毒生长受到阻抑。干扰素的缺点 1.皮下注射给药 2.不良反应常见 3.罕见HBsAg血清转换4.病毒变异与耐药 5.停药后易复发,干扰素治疗,干扰素对B细胞的功能，在一定条件下起抑制或增进作用，如干扰素浓度高时有明显抑制抗体反应，临床应用大剂量IFN-治疗慢性病毒性肝炎，可使血清IgG、IgM异常升高者得到改善或恢复，其作用亦系干扰素抑制B细胞的作用，使浆细胞制造免疫球蛋白抗体过多现象得到缓解所致。干扰素对效应细胞的作用，它可以增加HLA-1的表达，
3、这些抗原对杀伤性T细胞识别靶细胞是十分重要。此外还证实-IFN有增加IL-2受体作用，而IL-2又可增加有丝分裂刺激淋巴细胞诱生-IFN，故IL-2与-IFN在功能上有密切联系和协调作用。,核苷酸类治疗,核苷酸类药物作用于HBV的聚合酶区，通过取代病毒复制过程中延长聚合酶链所需的结构相似的核苷，终止链的延长，从而抑制病毒复制。治疗药物：1.拉米夫定(lamivudine) 2.阿德福韦酯 (adefovir dipivoxil) 3.恩替卡韦 (entecavir)4.替比夫定(telbivudine) 核苷类似物的缺点 1.无免疫调节作用 2.长期维持用药,干扰素与核苷类似物抗病毒（HBV）
4、治疗的比较：1.通过宿主免疫起作用 1.口服给药2.6-12个月，明确疗程 2.抑制HBV-DNA能力强3.无病毒变异和耐药 3.不良反应较少4.高HBeAg血清转换率 4.适合失代偿肝硬 化、器官移植等干 扰素的禁忌症5.可见HBsAg血清转换6.应答持久,免疫调节治疗,胸腺素（肽）具有能诱导T细胞成熟和调节成熟T细胞的功能。促进分泌IFN,IL-2,IL-3等，增加IL-2受体表达，以促进免疫缺陷的重建。Th1细胞因子利于病毒清除免疫效应CTL细胞内免疫治疗性疫苗,抗炎保肝治疗,肝脏炎症坏死及其所致的肝纤维化是疾病进展的主要病理学基础，因而如能有效抑制肝组织炎症，有可能减少肝细胞破坏和延缓
5、肝纤维化的发展。甘草酸制剂、水飞蓟素类等制剂活性成分比较明确，有不同程度的抗炎、抗氧化、保护肝细胞膜及细胞器等作用，临床应用这些制剂可改善肝脏生化学指标 (-2，II-3)。联苯双酯和双环醇等也可降低血清氨基转移酶特别是ALT 水平。,抗纤维化治疗,有研究表明，经IFN或核苷 (酸) 类似物抗病毒治疗后，肝组织病理学可见纤维化甚至肝硬化有所减轻，因此，抗病毒治疗是抗纤维化治疗的基础。根据中医学理论和临床经验，肝纤维化和肝硬化属正虚血瘀证范畴，因此，对慢性乙型肝炎肝纤维化及早期肝硬化的治疗，多以益气养阴、活血化瘀为主，兼以养血柔肝或滋补肝肾。,CD4+ CD25high cells can si
6、gnificantly inhibit the proliferation and cytokine secretion induced by TCR cross-linking of CD4+ CD25 responder T cells, CD8+ T cells, dendritic cells (DCs), natural killer (NK) cells, and B cells.An abundance of experimental data has confirmed that CD4+ CD25+ Tregs can suppress effective antiviral
7、 immune responses. Our study showed a positive correlation between CD4+ CD25+ Treg frequency and serum HBV DNA load, suggesting that the up-regulation of Tregs is associated with an increase in HBV replication. T,the frequency and functional properties of Tregs are important because increased number
8、s of Tregs might favour chronic virus development and influence the course of the disease. Chronic HBV infection is associated with impairment of the proliferative, cytokine production, and cytotoxic effector functions of HBV-specific T cells which probably contributes significantly to viral persist
9、ence, and CD4+ CD25+ Tregs have been found to inhibit effective virus-specific immune reactions,It has been reported that the polymorphisms of certain genes, such as CXCL10, intercellular adhesion molecule-1 (ICAM-1), TNF, etc., are associated with susceptibility to chronic hepatitis B virus infecti
10、on Chen et al. found that the expression of HBV in human hepatoplastoma cell line significantly down-regulated the expressions of MHC class I molecules and it was further observed that in murine chronic HBsAg carriers the expression of classical MHC-I molecules on hepatocytes was down-regulated,we h
11、ave demonstrated that KIR2DS2 and KIR2DS3 may act as HBV susceptive genes of chronic hepatitis B; whereas, KIR2DS1, KIR3DS1, and KIR2DL5 may be the protective genes that facilitate the clearance of HBV Asian cohorts have implicated the role of HLA allele DRB1*1302 in the clearance of HBV infection (
12、21-23). As KIR molecules modulate cell function upon the recognition of HLA class I, it can be inferred that KIR gene may also exert a crucial role in the pathogenesis of HBV infection.,PPAR has been shown to interact with HBV X-associated protein2 Presence of a variant PPAR molecule may render HBV-infected patients prone to HCC development. Interestingly, all patients carrying L162V polymorphism were infected with HBV and none of the HCV-infected patients had this polymorphism.,
