兒童乙肝的新認識(英文版)課件

1、NEW INSIGHT IN HEPATITIS B IN CHILDRENMei-Hwei Chang , M.D.Department of Pediatrics,National Taiwan University Hospital,Taipei, TAIWAN兒童乙肝的新認識(英文版）1NEW INSIGHT IN HEPATITIS B INReplication Cycle of HBV兒童乙肝的新認識(英文版）2Replication Cycle of HBV兒童乙肝的新EPIDEMIOLOGY兒童乙肝的新認識(英文版）3EPIDEMIOLOGY兒童乙肝的新認識(英文版）3Pre

2、valence of Chronic Hepatitis BHBsAg Prevalence 8% - High 2-8% - Intermediate 1.5xN 13% (4/31) 38% (24/64)Lai no limit 0% (0/30) 8% (5/60)Tsai, Hsu 2xN 38% (5/13) 44% (8/18)Sokal 2xN 11% (8/74) 26% (18/70)Meta-Ana no limit 11% (12/113) 23%(29/126)兒童乙肝的新認識(英文版）25 Effects of interferon in chEfficacy ac

3、cording to baseline ALT11/8843/1839/5833/974/178/1650%24%34%16%23%13% complete virologic response(HBeAg(-), HBV DNA(-)Jonas et al, N Engl J Med 2002; 346: 1706.兒童乙肝的新認識(英文版）26Efficacy according to baselineLamivudine paediatric phase 3 study (NUC30903)Placebo (n=97)Wk 52BaselineNo treatment (n=63)One

4、 year placebo controlled studyTwo yearfollow-on studyLamivudine 3 mg/kg (n=191)Lamivudine 3mg/kgHBeAg-veHBeAg+veTreatment (n=213)89% Durability of response at month 36 Sokal E et al. Hepatology. 2006; 43: 225-32.兒童乙肝的新認識(英文版）27Lamivudine paediatric phase 3 Long term lamivudine therapy for children w

5、ith HBeAg+ve CHB (2)Virologic response in the treatment arm 21% after 12 + 24 months of Rx (n=133) 30% after 0 + 24 months Rx (n=77) * VR = loss of HBeAg loss and HBV DNA The incidence of YMDD mutations was 64% (66/103) after 12 + 24 months of lamivudine 49% (34/70) after 0 + 24 months of lamivudine

6、 Sokal E et al. Hepatology. 2006; 43: 225-32. 兒童乙肝的新認識(英文版）28Long term lamivudine therapy f PREVENTION OF VIRAL HEPATITIS兒童乙肝的新認識(英文版）29 PREVENTION OF VIRA兒童乙肝的新認識(英文版）30兒童乙肝的新認識(英文版）30 IMPORTANT TRANSMISSION ROUTE IN HYPERENDEMIC AREAS : MOTHER TO CHILD EFFECTIVE PREVENTION OF HEPATITIS B :VACCINAT

7、ION IN INFANCY兒童乙肝的新認識(英文版）31 IMPORTANT THEPATITIS B VACCINATION AND CONTROL OF HEPATITIS B RELATED LIVER DISEASESAcute /Fulminant HepatitisChronic Hepatitis Liver Cirrhosis ?Hepatocellular Carcinoma兒童乙肝的新認識(英文版）32HEPATITIS B VACCINATION AND Universal HBV Vaccination and Decreased Mortality from Ful

8、minant Hepatitis in Infants in TaiwanUniversal HBV Vaccination July 1984Kao JH, Hsu HM, Shau WY, Chang MH, Chen DS. J Pediatr. 2001;139:349-52. *The average mortality rate per 105 infantsMortality Ratio: 3.2 (p 0.001)1974-1984: 5.36*1985-1998: 1.71*兒童乙肝的新認識(英文版）33Universal HBV Vaccination and Incide

9、nce Rate Ratios (IRR) of HBV-Positive v.s. -Negative FHF in 15 Years of the Universal Vaccination Program (Chen et al. Hepatology 2004 ;39:58-63) Year 198599,Case No. (Incidence per 10 5) P-ValueHBV(+) FHF43 1 Yr33 (0.74) 54.226.1, 123.2 0.01 1-15 Yr10 (0.014) 1-15 Yr 0.01 IRR(1 v.s. 1-15Y)95% C.I.H

10、BV (-) FHF 90% HBsAg Positive, 86% HBeAg Negative, HBV Genome Integration into Host Genome, 94% Maternal HBsAg PositiveChang MH et al. Hepatology 1991;13:316-20Chang MH et al. Cancer 1989; 64: 2377-80兒童乙肝的新認識(英文版）35Childhood HCCMale PredominanceEFFECT OF UNIVERSAL HEPATITIS B VACCINATION ON HCC IN T

11、AIWANESE CHILDREN, 6-9 YEARS Birth HCC Incidence Year in Children 1974-84 0.52/10 5 1984-86 0.13/10 5 Chang MH, et al. N Engl Med 1997; 336:1855-9.兒童乙肝的新認識(英文版）36EFFECT OF UNIVERSAL HEPATITIS Incidence of HCC in Children Diagnosed at Aged 6 to 14 Years from July 1981 to June 2000 According to Birth

12、Year Birth Population No. of Incidence R.R. 95% Year* Cases (per 10 5) CI1966-84 48,764,799 263 0.54 1 1984-94 17,817,510 35 0.20 0.36 0.26-0.52 _ * Birth Year was counted from July of one year to June of the next year. R.R.: risk ratio; CI: confidence interval. Chang MH, et al. Clin Cancer Res 2005

13、;11: 7953-7.兒童乙肝的新認識(英文版）37Incidence of HCC in Children DChang MH et al. JAMA2000;284:3040-42兒童乙肝的新認識(英文版）38Chang MH et al. JAMA2000;284:3Problems that remain to be solved for the control of Hepatitis & related DiseasesChang MH. Liver International 2003; 23: 309-14.Inadequate Resources2. Poor Compli

14、ance3. Vaccine Failure Intrauterine Infection Genetic Hyporesponsiveness Vaccine Escape Mutants / Variants兒童乙肝的新認識(英文版）39Problems that remain to be solACKNOWLEDGEMENT Hepatitis B Study : Hong-Yuan Hsu, Yen-Hsuan Ni, Huey-Ling Chen, Chien-Jen Chen, Ding-Shinn ChenHepatoma Study : Tony Chen, Hsu-Mei Hsu, Tzee-Chung Wu, Man-Shan Kong, Der-Cherng