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Prevention of Hepatitis B Virus Infection and Liver Cancer

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Viruses and Human Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 193))

Abstract

Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world, particularly in areas prevalent for HBV infection such as Asia, Africa, southern part of Eastern and Central Europe, and the Middle East. Risk factors of HBV-related HCC include (1) viral factors—persistent high viral replication, HBV genotype C or D, pre-S2 or core promoter mutants; (2) host factors—older age (>40 years old) at HBeAg seroconversion, male gender; (3) mother-to-infant transmission; and (4) other carcinogenic factors—smoking, habitual use of alcohol, etc. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective. Its cancer preventive efficacy supports it as the first successful example of cancer preventive vaccine in human. This experience can be extended to the development of other cancer preventive vaccine. Careful basic and clinical research is needed to develop ideal vaccines to induce adequate protection. Understanding the main transmission route and age at primary infection may help to set the optimal target age to start a new cancer preventive vaccination program. Besides timely HBV vaccination, the earlier administration of hepatitis B immunoglobulin immediately after birth, and even antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are possible strategies to enhance the prevention efficacy of HBV infection and its related liver cancer.

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References

  • Beasley RP (1982) Hepatitis B virus as the etiologic agent in hepatocellular carcinoma: epidemiologic considerations. Hepatology 2:21s–26s

    Google Scholar 

  • Beasley RP, Hwang LY, Lin CC et al (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22707 men in Taiwan. Lancet 2:1129–1133

    Article  PubMed  CAS  Google Scholar 

  • Beasley RP, Trepo C, Stevens CE et al (1977) The e antigen and vertical transmission of hepatitis B surface antigen. Amer J Epidemiol 105:94–98

    CAS  Google Scholar 

  • Braitenstein S, Dimitroulis D, Petrowsky H et al (2009) Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg 96:975–981

    Article  Google Scholar 

  • Bosch FX, Ribes J (2002) The epidemiology of primary liver cancer: global epidemiology. In: Tabor E (ed) Viruses and liver cancer. Elsevier, Amsterdam, pp 1–16

    Chapter  Google Scholar 

  • Bruix J, Boix L, Sala M et al (2004) Focus on hepatocellular carcinoma. Cancer Cell 5:215–219

    Article  PubMed  CAS  Google Scholar 

  • Bruix J, Sherman M (2005) Management of hepatocellular carcinoma AASLD Guideline recommendations for HCC screening. Hepatology 42:1208–1236

    Article  PubMed  Google Scholar 

  • Chang MH, Chen CJ, Lai MS et al (1997) Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 336:1855–1859

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, Chen DS, Hsu HC et al (1989) Maternal transmission of hepatitis B virus in childhood hepatocellular carcinoma. Cancer 64:2377–2380

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, Chen PJ, Chen JY et al (1991) Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood. Heptology 13:316–320

    Article  CAS  Google Scholar 

  • Chang MH, Chen TH, Hsu HM et al (2005) Problems in the prevention of childhood hepatocellular carcinoma in the era of universal hepatitis B immunization. Clin Cancer Res 11:7953–7957

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, Hsu HC, Lee CY et al (1984) Fraternal hepatocellular carcinoma in young children in two families. Cancer 53:1807–1810

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, Hsu HY, Huang LM et al (1996) The role of transplacental hepatitis B core antibody in the mother-to-infant transmission of hepatitis B virus. J Hepatol 24:674–679

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, Shau WY, Chen CJ et al (2000) The effect of universal hepatitis B vaccination on hepatocellular carcinoma rates in boys and girls. JAMA 284:3040–3042

    Article  PubMed  CAS  Google Scholar 

  • Chang MH, You SL, Chen CJ et al (2009) Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst 101:1348–1355

    Article  PubMed  CAS  Google Scholar 

  • Chen CJ, Yang HI, Su J et al (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295:65–73

    Article  PubMed  CAS  Google Scholar 

  • Chen CL, Yang HI, Yang WS et al (2008) Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 135:111–121

    Article  PubMed  CAS  Google Scholar 

  • Chen DS, Hsu NHM, Sung JL et al (1987) A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers. JAMA 257:2597–2603

    Article  PubMed  CAS  Google Scholar 

  • Chen HL, Chang MH, Ni YH et al (1996) Seroepidemiology of hepatitis B virus infection in children: ten years after a hepatitis B mass vaccination program in Taiwan. JAMA 276:906–908

    Article  PubMed  CAS  Google Scholar 

  • Chen HL, Lin LH, Hu FC et al (2012) Effects of maternal screening and universal immunization to prevent mother- to-infant transmission of HBV. Gastroenterology 142:773–781

    Article  PubMed  Google Scholar 

  • Chen YC, Chu CM, Liaw YF (2010) Age- specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology 51:435–444

    Article  PubMed  Google Scholar 

  • Chien MC, Tong MJ, Lo KJ et al (1981) Hepatitis B viral markers in patients with primary hepatocellular carcinoma in Taiwan. J Natl Cancer Inst 66:475–479

    PubMed  CAS  Google Scholar 

  • Da Villa G, Picciottoc L, Elia S et al (1995) Hepatitis B vaccination: universal vaccination of newborn babies and children at 12 years of age versus high risk groups: a comparison in the field. Vaccine 13:1240–1243

    Article  PubMed  Google Scholar 

  • Egner PA, Wang JB, Shu YR et al (2001) Chlorophyline intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci USA 98:14601–14606

    Article  PubMed  CAS  Google Scholar 

  • Feret E, Larouze B, Diop B et al (1987) Epidemiology of hepatitis B virus infection in the rural community of tip, Senegal. Am J Epidemiol 125:140–149

    PubMed  CAS  Google Scholar 

  • Ferlay J, Parkin DM, Curado MP, et al (2010) Cancer incidence in five continents, Volumes I to IX: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. [http://ci5.iarc.fr, accessed 26 Jan 2012]

  • Grisham JW (2001) Molecular genetic alterations in primary hepatocellular neoplasms. In: Coleman WB, Tsongalis GJ (eds) The molecular basis of human cancer. Humana Press, Totowa, pp 269–346

    Google Scholar 

  • Han GR, Cao MK, Zhao W et al (2011) A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J Hepatol 55:1215–1221

    Article  PubMed  CAS  Google Scholar 

  • Halsey NA, Duclos P, van Damme P et al (1999) Hepatitis B vaccine and central nervous system demyelinating diseases. Pediatrc Infect Dis J 18:23–24

    Article  CAS  Google Scholar 

  • Heyward WL, Lanier AP, Bender TR et al (1981) Primary hepatocellular carcinoma in Alaskan natives, 1969–1979. Int J Cancer 28:47–50

    Article  PubMed  CAS  Google Scholar 

  • Hsu HY, Chang MH, Ni YH, Chen HL (2004) Survey of hepatitis B surface variant infection in children 15 years after nationwide vaccination program in Taiwan. Gut 53:1499–503

    Google Scholar 

  • Hsu HC, Lin WS, Tsai MJ (1983) Hepatitis B surface antigen and hepatocellular carcinoma in Taiwan. With special reference to types and localization of HBsAg in the tumor cells. Cancer 52:1825–1832

    Article  PubMed  CAS  Google Scholar 

  • Hsu HY, Chang MH, Chen DS et al (1986) Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan. J Med Virol 18:301–307

    Article  PubMed  CAS  Google Scholar 

  • Hsu HY, Chang MH, Hsieh KH et al (1992) Cellular immune response to hepatitis B core antigen in maternal-infant transmission of hepatitis B virus. Hepatology 15:770–776

    Article  PubMed  CAS  Google Scholar 

  • Hsu HY, Chang MH, Liaw SH et al (1999) Changes of hepatitis B surface variants in carrier children before and after universal vaccination in Taiwan. Hepatology 30:1312–1317

    Article  PubMed  CAS  Google Scholar 

  • Hsu HY, Chang MH, Ni YH et al (2010) Twenty-year trends in the emergence of hepatitis B surface antigen variants in children and adolescents after universal vaccination in Taiwan. J Infect Dis 201:1192–1200

    Article  PubMed  Google Scholar 

  • Jacobson LP, Zhang BC, Shu YR et al (1997) Oltipratz chemoprevention trial in Qidong, People’s Republic of China: study design and clinical outcomes. Cancer Epidemiol Biomarkers Prev 6:257–265

    PubMed  CAS  Google Scholar 

  • Jang MK, Lee JY, Lee JH et al (2001) Seroepidemiology of HBV infection in South Korea, 1995 through 1999. Korean J Intern Med 16:153–159

    PubMed  CAS  Google Scholar 

  • Jee SH, Ohrr H, Sull JW et al (2004) Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 96:1851–1855

    Article  PubMed  Google Scholar 

  • Kane MA (1996) Global status of hepatitis B immunization. Lancet 348:696

    Article  PubMed  CAS  Google Scholar 

  • Kane MA, Brooks A (2002) New immunization initiatives and progress toward the global control of hepatitis B. Curr Opin Infect Dis 15:465–469

    Article  PubMed  Google Scholar 

  • Lavanchy D (2004) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepatitis 11:97–107

    Article  CAS  Google Scholar 

  • Lavanchy D (2008) Chronic viral hepatitis as a public health issue in the world. Best Pract Res Clin Gastroenterol 22:991–1008

    Article  PubMed  Google Scholar 

  • Lee SD, Lo KJ, Wu JC et al (1986) Prevention of maternal-infant hepatitis B virus transmission by immunization: the role of serum hepatitis B virus DNA. Hepatology 6(3):369–73

    Google Scholar 

  • Liaw YF, Sung JJ, Chow WC et al (2004) Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 351:1521–1531

    Article  PubMed  CAS  Google Scholar 

  • Liaw YF (2011) Impact of hepatitis B therapy on the long-term outcome of liver disease. Liver Int Suppl 1:117–121

    Article  Google Scholar 

  • Lin HH, Chang MH, Chen DS et al (1991) Early predictor of the efficacy of immunoprophylaxis against perinatal hepatitis B transmission: analysis of prophylaxis failure. Vaccine 9:457–460

    Article  PubMed  CAS  Google Scholar 

  • Lin HH, Lee TY, Chen DS et al (1987) Transplacental leakage of HBeAg-positive maternal blood as the most likely route in causing intrauterine infection with hepatitis intrauterine infection with hepatitis B virus. J Pediatr 111:877–881

    Article  PubMed  CAS  Google Scholar 

  • Lin SM, Yu ML, Lee CM et al (2007) Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 46:45–52

    Article  PubMed  CAS  Google Scholar 

  • Livingston SE, Simonetti J, McMahon B et al (2007) Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis 195(5–11):1

    Google Scholar 

  • McMahon BJ, Bulkow LR, Singleton RJ et al (2011) Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology 54:801–807

    Article  PubMed  Google Scholar 

  • Montesano R (2011) Preventing primary liver cancer: the HBV vaccination project in the Gambia (West Africa). Environ Health 10(Suppl 1):S6

    Article  PubMed  Google Scholar 

  • Ni YH, Chang MH, Hsu HY et al (1991) Hepatocellular carcinoma in childhood. Clinical manifestations and prognosis. Cancer 68:1737–1741

    Article  PubMed  CAS  Google Scholar 

  • Ni YH, Chang MH, Huang LM et al (2001) Hepatitis B virus infection in children and adolescents in an hyperendemic area: 15 years after universal hepatitis B vaccination. Ann Intern Med 135:796–800

    Article  PubMed  CAS  Google Scholar 

  • Ni YH, Huang LM, Chang MH et al (2007) Two decades of universal hepatitis B vaccination in Taiwan: impact and implication for future strategies. Gastroenterology 132:1287–1293

    Article  PubMed  Google Scholar 

  • Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156

    Article  PubMed  CAS  Google Scholar 

  • Poovorawan Y, Sanpavat S, Pongpunlert W et al (1989) Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers. JAMA 261:3278–3281

    Article  PubMed  CAS  Google Scholar 

  • Schafer DF, Sorrell MF (1999) Hepatocellular carcinoma. Lancet 353:1253–1257

    Article  PubMed  CAS  Google Scholar 

  • Shepard CW, Simard EP, Finelli L et al (2006) Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 28:112–125

    Article  PubMed  Google Scholar 

  • Stevens CE, Beasley RP, Tsui J et al (1975) Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 292:771–774

    Article  PubMed  CAS  Google Scholar 

  • Tang JR, Hsu HY, Lin HH et al (1998) Hepatitis B surface antigenemia at birth: a long-term follow-up study. J Pediatr 133:374–377

    Article  PubMed  CAS  Google Scholar 

  • Tseng TC, Liu CJ, Yang HC et al (2012) High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 142:1140–1149

    Article  PubMed  CAS  Google Scholar 

  • Tsuei DJ, Hsu HC, Lee PH et al (2004) RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts. Oncogene 29(23):5815–5822

    Article  Google Scholar 

  • Turati F, Edefonti V, Talamini R et al (2012) Family history of liver cancer and hepatocellular carcinoma. Hepatology 55:1416–1425

    Article  PubMed  Google Scholar 

  • Van Herck K, Vorsters A, Van Damme P (2008) Prevention of viral hepatitis (B and C) reassessed. Best Pract Res Clin Gastroenterol 22:1009–1029

    Article  PubMed  Google Scholar 

  • van Zonneveld M, van Nunen AB, Niesters HG et al (2003) Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat 10:294–297

    Article  PubMed  Google Scholar 

  • Villanueva A, Newell P, Chiang DY et al (2007) Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27:55–76

    Article  PubMed  CAS  Google Scholar 

  • Wang HC, Huang W, Lai MD et al (2006) Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci 97:683–688

    Article  PubMed  CAS  Google Scholar 

  • Whittle H, Jaffar S, Wansbrough M et al (2002) Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. BMJ 325:569–573

    Article  PubMed  Google Scholar 

  • Wichajarn K, Kosalaraksa P, Wiangnon S (2008) Incidence of hepatocellular carcinoma in children in Khon Kaen before and after national hepatitis B vaccine program. Asian Pac J Cancer Prev 9:507–509

    PubMed  Google Scholar 

  • World Health Organization (2012) Data, statistics and graphics. Global routine vaccination coverage, (http://www.who.int/immunization_monitoring/data/en/, accessed Mar 2012)

  • Xu WM, Cui YT, Wang L et al (2009) Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat 16:94–103

    Article  PubMed  Google Scholar 

  • Yang HI, Lu SN, Liaw YF et al (2002) Hepatitis B e antigen and the risks of hepatocellular carcinoma. N Engl J Med 347:168–174

    Article  PubMed  CAS  Google Scholar 

  • Yeh SH, Chen PJ (2012) Gender disparity of hepatocellular carcinoma: the roles of sex hormones. Oncology 78(suppl 1):172–179

    Google Scholar 

  • Yu MW, Hsu FC, Sheen IS et al (1997) Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 145:1039–1047

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work was supported by grants from the National Health Research Institute, Taiwan.

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Correspondence to Mei-Hwei Chang .

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Chang, MH. (2014). Prevention of Hepatitis B Virus Infection and Liver Cancer. In: Chang, M., Jeang, KT. (eds) Viruses and Human Cancer. Recent Results in Cancer Research, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38965-8_5

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  • DOI: https://doi.org/10.1007/978-3-642-38965-8_5

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