Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study.

BACKGROUND Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts. METHODS Data on 1958 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus. RESULTS Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6-19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11). CONCLUSION The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.

[1]  Chien-Jen Chen,et al.  Prevention of Hepatocellular Carcinoma by Universal Vaccination against Hepatitis B Virus: The Effect and Problems , 2005, Clinical Cancer Research.

[2]  K. Reddy,et al.  Hepatitis C virus infection and hepatocellular carcinoma. , 2008, Clinics in liver disease.

[3]  T. Baumann.  New treatment for harvest mite infestation. , 2001, Archives of internal medicine.

[4]  Mei-Hwei Chang,et al.  Minimal role of hepatitis C virus infection in childhood liver diseases in an area hyperendemic for hepatitis B infection , 1993, Journal of medical virology.

[5]  E. Lustbader,et al.  HOST RESPONSES TO HEPATITIS-B INFECTION IN PATIENTS WITH PRIMARY HEPATIC CARCINOMA AND THEIR FAMILIES A Case/Control Study in Senegal, West Africa , 1976, The Lancet.

[6]  H. Hsu,et al.  Hepatitis B surface antigenemia at birth: a long-term follow-up study. , 1998, The Journal of pediatrics.

[7]  M. Manns,et al.  A Mitochondrial Antigen‐Antibody System in Cholestatic Liver Disease Detected by Radioimmunoassay , 2007, Hepatology.

[8]  H. Hsu,et al.  Hepatocellular carcinoma in childhood. Clinical manifestations and prognosis , 1991, Cancer.

[9]  Lu-Yu Hwang,et al.  HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS A Prospective Study of 22 707 Men in Taiwan , 1981, The Lancet.

[10]  H. Hsu,et al.  Hepatitis B Virus Infection in Children and Adolescents in a Hyperendemic Area: 15 Years after Mass Hepatitis B Vaccination , 2001, Annals of Internal Medicine.

[11]  M. Chang,et al.  Hepatoblastoma in infancy and childhood: a clinical and pathological study of 32 cases. , 1991, Zhonghua Minguo xiao er ke yi xue hui za zhi [Journal]. Zhonghua Minguo xiao er ke yi xue hui.

[12]  M. Lai,et al.  Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. , 1997, The New England journal of medicine.

[13]  N. Breslow,et al.  Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. , 1987, IARC scientific publications.

[14]  Chien-Jen Chen,et al.  Risk of hepatocellular carcinoma and habits of alcohol drinking, betel quid chewing and cigarette smoking: a cohort of 2416 HBsAg-seropositive and 9421 HBsAg-seronegative male residents in Taiwan , 2003, Cancer Causes & Control.

[15]  Ding‐Shinn Chen,et al.  Mutation of p53 gene in hepatocellular carcinoma in Taiwan. , 1992, Cancer Research.

[16]  P. Hainaut,et al.  The aflatoxin-induced TP53 mutation at codon 249 (R249S): biomarker of exposure, early detection and target for therapy. , 2009, Cancer letters.

[17]  Ding‐Shinn Chen.  Hepatitis B Virus Infection, Its Sequelae, and Prevention in Taiwan , 1987 .

[18]  Sheng-Nan Lu,et al.  Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection , 1999, Cancer.

[19]  F. X. Bosch,et al.  The epidemiology of primary liver cancer: global epidemiology , 2002 .

[20]  C. Yen,et al.  Two decades of universal hepatitis B vaccination in taiwan: impact and implication for future strategies. , 2007, Gastroenterology.

[21]  J. Sung,et al.  A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers. , 1987, JAMA.

[22]  H. Adami,et al.  The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, or cirrhosis , 2001, Hepatology.

[23]  Mei-Hwei Chang,et al.  Hepatitis B virus integration in hepatitis B virus‐related hepatocellular carcinoma in childhood , 1991, Hepatology.

[24]  H. Hsu,et al.  Maternal transmission of hepatitis B virus in childhood hepatocellular carcinoma , 1989, Cancer.

[25]  SY Chou,et al.  Prevalence of Smoking, Alcohol Consumption, Betel Nut Chewing and Illicit Drug Use among Adolescents in Taiwan;台灣地區在校青少年吸煙、喝酒及嚼食檳榔與藥物使用之盛行率 , 2006 .

[26]  Grace Huang,et al.  Aspirin as an Adjunct to Screening for Prevention of Sporadic Colorectal Cancer: A Cost-Effectiveness Analysis , 2001, Annals of Internal Medicine.