兒童乙肝的新認(rèn)識(shí)英文版

1、兒童乙肝的新認(rèn)識(shí)英文版Replication Cycle of HBVEPIDEMIOLOGYPrevalence 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)Effi

2、cacy according 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.Lamivudine paediatric phase 3 study (NUC30903)Placebo (n=97)Wk 52BaselineNo treatment (n=63)One year placebo controlled studyTwo year

3、follow-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.Long term lamivudine therapy for children with HBeAg+ve CHB (2)Virologic response in the treatment arm 21% after 12 + 24 month

4、s 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 Sokal E et al. Hepatology. 2006; 43: 225-32. PREVENTION OF VIRAL HEPATITIS IMPORTA

5、NT TRANSMISSION ROUTE IN HYPERENDEMIC AREAS : MOTHER TO CHILD EFFECTIVE PREVENTION OF HEPATITIS B :VACCINATION IN INFANCYHEPATITIS B VACCINATION AND CONTROL OF HEPATITIS B RELATED LIVER DISEASESAcute /Fulminant HepatitisChronic Hepatitis Liver Cirrhosis ?Hepatocellular CarcinomaUniversal HBV Vaccina

6、tion and Decreased Mortality from Fulminant 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* Incidence Rat

7、e 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.HBV (-)

8、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: 2377-80EFFECT OF UNIVERSAL HEPATITIS B VACCINATION ON HCC IN TAIWANESE CHILDREN, 6-9 YEARS Birth HCC Incidence Yea

9、r 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.Incidence of HCC in Children Diagnosed at Aged 6 to 14 Years from July 1981 to June 2000 According to Birth Year Birth Population No. of Incidence R.R. 95% Year* Cases (per 10 5) CI1966-84 48,764,799 263 0

10、.54 1 1984-94 17,817,510 35 0.20 0.36 _ * 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;11: 7953-7.Chang MH et al. JAMA2000;284:3040-42Problems that remain to be solved for the control of Hepati

11、tis & related DiseasesChang MH. Liver International 2003; 23: 309-14.Inadequate Resources2. Poor Compliance3. Vaccine Failure Intrauterine Infection Genetic Hyporesponsiveness Vaccine Escape Mutants / VariantsACKNOWLEDGEMENT Hepatitis B Study : Hong-Yuan Hsu, Yen-Hsuan Ni, Huey-Ling Chen, Chien-Jen Chen, Ding-Shinn ChenHepatoma Study : Tony Chen, Hsu-Mei Hsu