核苷酸类药物抗慢性乙肝及耐药监测课件.ppt

核苷（酸）类药物抗慢乙肝治疗及耐药监测 上海 瑞金医院 感染科 张欣欣 教授 治疗失败的原因 HBV准种的演变 Patient: Mr. JCH, 40 y No treatment Sheldon J, et al. J Viral Hep 2006; 13:427–434 Locarnini S. J Hepatol 2003; 39:S124–S132 Drug resistant mutants selected and replicated Anti-viral treatment Pre-exist mutants Chen L,… Zhang XX et al. 2009 J Hepatol 拉米夫定治疗过程中HBV准种演变 与抗病毒治疗应答 LAM Dynamic evolution of HBV quas within RT region in the first 4 w during lam treatment in two representative patients retrieved from R (left) and NR (right). Both of them were infected genotype C virus. The vertical bars indicate the number and the proportion of viral quas within each sample. Each color represents one kind of quas. The same color in different time point means identical quasispecies. An interesting case Indicate that the analysis of qus may be more sensitive and accurate than viral load. HBeAg+ HBeAg-/anti-HBe+ (precore/core promoter variants) ALT HBV DNA Normal/mild CH Moderate/severe CH Moderate/severe CH Normal/mild CH Cirrhosis Immune Tolerance Immune Clearance Low Replicative Phase Reactivation Phase Cirrhosis 2000 IU/mL 2000 IU/mL Inactive cirrhosis 2 x 108 - 2 x 1011 IU/mL 慢性 HBV 感染自然过程 Slide courtesy of A. S. F. Lok, MD. 200,000 - 2 x 109 IU/mL Inactive-carrier state HBeAg- chronic hepatitis HBeAg+ chronic hepatitis * * 慢乙肝抗病毒治疗药物不断问世 * 1992 IFN 被批准 CHB 治疗1 1998 LAM2 2002 2005 2007 2008 PegIFN5 ADV3 ETV6 LdT9 TDF10 2004 2006 4006研究：抗病毒疗法能减缓慢性乙型肝炎的病情进展4 REVEAL研究：揭示病毒载量与肝硬化/肝细胞性肝癌的关系7,8 *核准上市的首年 1. Zoulim F, et al. J Hepatol 2008;48(Suppl.1):S2–S19. 2. GSK. Zeffix? (LAMivudine) EU SPC. Feb 2007. 3. Gilead. Hepsera? (adefovir) EU SPC. 2008. 4. Liaw YF, et al. N Engl J Med 2004;351:1521–1531. 5 Roche. Pegasys? (pegylated interferon alfa-2a) EU SPC. Jun 2007. 6. BMS. Baraclude? (entecavir) SPC. Jan 2008. 7. Chen CJ, et al. JAMA 2006;295:65–73. 8. Iloeje U, et al. Gastroenterology 2006;130:678–686. 9. Novartis. Sebivo? (telbivudine) EU SPC. Feb 2007. 10. Gilead. Viread? (teno