感染病学（上海交通大学）NO3病毒性肝炎.pptVIP

* HBV的示意图 HBV是大的、球形病毒颗粒，也叫Dane颗粒。它含有20面立方体的核心，包裹在含HBV表面抗原（HBsAg）的脂蛋白外衣中。 病毒颗粒中央的核心颗粒是由DNA基因组、DNA聚合酶、HBeAg，以及外面包裹的核心抗原（HBcAg）组成。HBeAg在血液中是可溶性，通过血清分析能很容易地检测到。但HBcAg仅能通过肝组织染色才能检出。 * 30 * 31 * * 大剂量、长疗程?干扰素治疗可以显著改善肝组织炎症 Knodell指数为定量评估慢性肝炎肝组织活检标本的组织学变化的评分系统，分值越接近0，炎症反应越轻。 * ?干扰素治疗组累积生存率显著长于对照组 * 治疗组HCC为1/67（1.5％）；对照组为4/34（12％），p=0.043 HCC累积发生率对照组显著高于治疗组，p＝0.013 * Key message Following infection by the hepatitis B virus, the entire virion enters the hepatocyte. The partially double-stranded DNA converted to a complete double-stranded DNA, transported to the nucleus and supercoiled - the covalently closed circular DNA or cccDNA.  The cccDNA is extremely stable and is the template from which the virus replicates and generates viral proteins. This is done through a full length messenger RNA template and 3 smaller mRNA templates. The viral proteins are produced from the 3 smaller mRNA transcript on the host endoplasmic reticulum. The HBV DNA polymerase then binds to the full length mRNA and orchestrates the formation of an encapulated mRNA/polymerase complex and subsequent replication.  Within the nucleocaspid complex, the mRNA is reverse transcribed (RT) into a minus strand DNA by the DNA polymerase and the mRNA is simultaneously degraded. The DNA polymerase then produces a partially double-stranded DNA. Some of the partially double-stranded DNA migrates to the endoplasmic reticulum where it forms complete infectious HBV virions. Additionally, some of the partially double stranded DNA may migrate to the nucleus where it forms further copies of cccDNA thus amplifying and replenishing the cccDNA pool in the nucleus of the infected hepatocytes We have direct evidence that lamivudine exerts its action at both the reverse transcription and the DNA polymerase stages of HBV replication. Lamivudine acts as a chain terminator after incorporation into the growing DNA chain.  Lamivudine may also exert its effect by inhibiting the completion of the double-stranded DNA and henc