Prevention

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Prevention

The single most important strategy to prevent hepatocellular carcinoma (the most common liver cancer) is to prevent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). Prevention of HBV- and HCV-related hepatocellular carcinoma is also possible through effective treatment of the viral infection. See the Screening section of this chapter for more information.

Vaccination of all infants and adults in high-risk groups is the most effective preventive approach against HBV, with demonstrated long-term efficacy and benefits, including a reduction in hepatitis B notification rates in Australia.

Other effective primary prevention strategies include ensuring a safe blood supply, universal precautions against blood contamination in healthcare settings and harm reduction approaches to reduce transmission from injecting drug use.

Reducing exposure to other factors that increase the risk of developing chronic liver disease, such as alcohol and aflatoxins, also will reduce the proportion of infected people who develop chronic liver disease and hepatocellular carcinoma. Given the mounting evidence of the association of obesity, diabetes and non-alcoholic fatty liver disease with hepatocellular carcinoma, strategies to reduce the prevalence of obesity and related metabolic risk factors will become increasingly necessary. For individuals with hemochromatosis, family screening, early diagnosis and correcting iron overload can prevent liver fibrosis and hence progression to hepatocellular carcinoma. Research is continuing to determine the potential hepatoprotective effect of coffee intake.

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Hepatitis B vaccination

Efficacy and safety

An HBV vaccine has been available since 1982. The complete hepatitis B vaccine schedule induces protective antibody levels in more than 95% of infants, children and young adults[1][2]. Response to the vaccine declines with age: after age 40, protective antibody levels are achieved in 90% of those vaccinated; at age 60, protection drops to 65–75%[3].

Vaccine induced antibody levels against HBsAg decline with time, however this does not appear to be clinically important. Booster doses are not recommended in immuno-competent individuals after full vaccination, as there is good evidence that a completed primary course of hepatitis B vaccination provides long-lasting protection[4][5]. This applies to children and adults, including those at risk of occupational exposure[5][6][7]. In Australia, booster doses are recommended only for individuals with impaired immunity[5].

According to the World Health Organization (WHO), worldwide experience with the hepatitis B vaccine (administration of over 1 billion doses since 1982) and extensive reviews by independent expert committees, such as the Global Advisory Committee on Vaccine Safety, the vaccine has an outstanding record of safety and effectiveness. Adverse events after hepatitis B vaccination are generally transient and minor; the most common are soreness at the injection site (5%), low grade fever (2–3%), nausea, dizziness, malaise, myalgia and arthralgia[5]. The birth dose of hepatitis B vaccine is well tolerated by newborn infants, however fever can occur in a small proportion of cases (0.6–3.7%)[5]. It does not interfere with either the establishment or maintenance of breastfeeding[8][9]. After a comprehensive review in 2002, WHO stated that there was no conclusive evidence of a link between hepatitis B vaccination and multiple sclerosis[10].

The vaccine is neither therapeutic nor has adverse events in people infected with HBV. It is safe in those already immune to HBV[5].

Benefits

The effect of vaccination on infection rates in vaccinated age cohorts has been reported in many countries, and already some countries with previously very high hepatocellular carcinoma rates, such as Taiwan, have observed statistically significant reductions in young, vaccinated age groups. Taiwan was the first country to vaccinate newborns against HBV and give immunoglobulin at birth to infants of high-risk mothers (in 1984). Following implementation of this strategy, the number of HBV infections and the incidence of hepatocellular carcinoma among children have been greatly reduced[11], establishing the hepatitis B vaccine as the first vaccine that could prevent cancer in humans[12].

There is evidence that universal immunisation of infants and children in Australia is having an impact on acute hepatitis B notifications. Since the introduction of the vaccination programs, there has been a general decline in overall hepatitis B notification rates, especially among people aged 15–29 years[13]. Between 2000 and 2010 the rate of newly acquired HBV more than halved from a rate of 2.2 per 100,000 to 1.0, and unspecified hepatitis B rates decreased by 22%[13]. It is likely that these declining rates also reflect changing practices among other high-risk groups, such as sex workers and PWID.

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Other strategies for preventing virus transmission

Ensuring safe blood supply

Transmission of hepatitis in healthcare settings has been greatly reduced due to the introduction of screening of blood donations prior to transfusion, or manufacture of blood products, and screening of organ donors prior to transplant[14]. The Australian Red Cross Blood Service (ARCBS) introduced screening of blood products for HBV antigens in 1970–71, for HBV DNA in 2010, for HCV antibodies in 1990 and for HCV RNA in 2000.

Since the 1990s the ARCBS, under regulation of the Therapeutic Goods Administration, has been required to ensure all applicants for blood donation are screened through a series of questions in order to minimise the risk of transmission of infectious diseases.

As well as testing for HBV and HCV, the ARCBS test blood donations for HIV, Human T-cell Lymphotropic Virus and syphilis.

Universal precautions in healthcare settings

The use of standard precautions in the clinical setting to minimise transmission of blood-borne viruses and other infection control measures has further minimised the risk of hepatitis transmission in healthcare settings. Standard practices include the use of disposable equipment, sterilisation of multi-use equipment, gloving to handle wounds and blood products, and the correct disposal of sharps, body fluids and body parts.

Harm reduction

In 2010, 39% of newly acquired HBV cases and 79% of newly acquired HCV cases were associated with injecting drug use[13]. These figures are generally understood to be a considerable under-estimation of the actual attributable fractions (particularly for HCV) as there is significant non-reporting. Studies suggest knowledge about hepatitis is poor among this high-risk population[15] and most do not complete vaccination regimens[16].

Measures to prevent transmission of bloodborne viruses among PWID include education programs, harm reduction through needle and syringe exchange programs, safe injecting rooms, and special programs for prisoners. Australian Government investment in needle and syringe programs between 2000 and 2009 was estimated to have prevented nearly 97,000 cases of hepatitis C (and more than 32,000 new HIV infections) and saved $1.28 billion in direct healthcare costs[17]. Following systematic reviews of the evidence, the Guidance on Prevention of Viral Hepatitis B and C Among People Who Inject Drugs, produced by WHO, recommends peer interventions and provision of low dead-space syringes by needle and syringe programs, in addition to a rapid vaccination regimen and incentives to complete HBV vaccination, to reduce the incidence of viral hepatitis[18].

Transmission of hepatitis B in adults often occurs through sexual contact. Randomised controlled trials show vaccination of sexually active adults effectively prevents transmission[19], but given that adult infection with HBV does not commonly result in chronic infection, vaccination of all sexually active adults would have very little impact on the incidence of hepatocellular carcinoma.

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Prevention of non-viral liver diseases

Alcoholic cirrhosis

Evidence shows hepatocellular carcinoma complicates alcoholic cirrhosis at a rate of approximately 1% per annum[20]. As such, prevention of alcoholic liver disease by curbing alcohol intake has the potential to lower rates of hepatocellular carcinoma in countries where alcohol dependence is high[21].

See the Alcohol chapter of the National Cancer Prevention Policy for more information on the link between alcohol and cancer.

Obesity and metabolic factors

As further evidence of the association of obesity, diabetes and NAFLD with hepatocellular carcinoma emerges, action is needed to prevent a significant ‘metabolic’ hepatocellular carcinoma burden in the future, including strategies aimed at reducing obesity through improved diet and physical activity.

See the Obesity and overweight, physical inactivity and nutrition chapter of the National Cancer Prevention Policy for more information on the link between these factors and cancer.

Haemochromatosis

Early detection of haemochromatosis, and correction of hepatic iron overload before development of advanced stage fibrosis, prevents complications including hepatocellular carcinoma[22].

Haemochromatosis is easily detected by serum markers of iron overload and genetic screening of family members. Correction of hepatic iron overload by venesection before development of advanced stage fibrosis is an important strategy to prevent hepatocellular carcinoma[21].

Coffee intake

Several observational studies have shown a hepatoprotective effect of coffee drinking, showing that an association with a reduced risk of hepatocellular carcinoma[23]. The mechanisms of this action and the exact amount of coffee consumption necessary to obtain a benefit are the subject of continuing research. Coffee drinking may protect against hepatocellular carcinoma by reducing insulin levels and thereby type 2 diabetes risk[24], which is now an established risk factor[25]. In patients with chronic HCV infection, consumption of high levels of caffeine has been associated with milder fibrosis[26].

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References

  1. Floreani A, Baldo V, Cristofoletti M, Renzulli G, Valeri A, Zanetti C, et al. Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. Vaccine 2004 Jan 26;22(5-6):607-10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14741151.
  2. Bialek SR, Bower WA, Novak R, Helgenberger L, Auerbach SB, Williams IT, et al. Persistence of protection against hepatitis B virus infection among adolescents vaccinated with recombinant hepatitis B vaccine beginning at birth: a 15-year follow-up study. Pediatr Infect Dis J 2008 Oct;27(10):881-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18756185.
  3. Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H. Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med 1998 Jul;15(1):1-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9651632.
  4. van der Sande MA, Waight P, Mendy M, Rayco-Solon P, Hutt P, Fulford T, et al. Long-term protection against carriage of hepatitis B virus after infant vaccination. J Infect Dis 2006 Jun 1;193(11):1528-35 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16652281.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Australian Government Department of Health and Ageing. The Australian immunisation handbook. 10th edition. Canberra: DoHA; 2013 Available from: http://health.gov.au/internet/immunise/publishing.nsf/Content/EE1905BC65D40BCFCA257B26007FC8CA/$File/handbook10.pdf.
  6. Petersen KM, Bulkow LR, McMahon BJ, Zanis C, Getty M, Peters H, et al. Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth. Pediatr Infect Dis J 2004 Jul;23(7):650-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15247604.
  7. Fitzsimons D, François G, Hall A, McMahon B, Meheus A, Zanetti A, et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 2005 Jul 14;23(32):4158-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15964484.
  8. Eriksen EM, Perlman JA, Miller A, Marcy SM, Lee H, Vadheim C, et al. Lack of association between hepatitis B birth immunization and neonatal death: a population-based study from the vaccine safety datalink project. Pediatr Infect Dis J 2004 Jul;23(7):656-62 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15247605.
  9. Global Advisory Committee on Vaccine Safety. The global advisory committee on vaccine safety rejects association between hepatitis B vaccination and multiple sclerosis. Geneva, Switzerland: WHO; 2002 Nov Available from: http://www.who.int/vaccine_safety/committee/topics/hepatitisb/ms/en/.
  10. Chang MH. Hepatitis B virus and cancer prevention. Recent Results Cancer Res 2011;188:75-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21253790.
  11. Taiwan Hepatoma Study Group, Chang MH, You SL, Chen CJ, Liu CJ, Lee CM, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst 2009 Oct 7;101(19):1348-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19759364.
  12. 13.0 13.1 13.2 NNDSS Annual Report Writing Group. Australia's notifiable disease status, 2010: Annual report of the National Notifiable Diseases Surveillance System. Commun Dis Intell 2012 Mar 31;36(1):1-69 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23153082.
  13. Hilleman MR. Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus. Vaccine 2003 Dec 1;21(32):4626-49 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14585670.
  14. Day C, White B, Ross J, Dolan K. Poor knowledge and low coverage of hepatitis B vaccination among injecting drug users in Sydney. Aust N Z J Public Health 2003 Oct;27(5):558 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14651407.
  15. Maher L, Chant K, Jalaludin B, Sargent P. Risk behaviors and antibody hepatitis B and C prevalence among injecting drug users in south-western Sydney, Australia. J Gastroenterol Hepatol 2004 Oct;19(10):1114-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15377287.
  16. National Centre for HIV Epidemiology and Clinical Research. Return on investment 2: evaluating the cost-effectiveness of needle and syringe programs in Australia. Sydney: NCHECR; 2009. Sponsored by Australian Government Department of Health and Ageing. Available from: http://www.health.gov.au/internet/main/publishing.nsf/content/C562D0E860733E9FCA257648000215C5/$File/return2.pdf.
  17. World Health Organization. Guidance on prevention of viral hepatitis B and C among people who inject drugs. Geneva, Switzerland: WHO; 2012 Jul. Sponsored by U.S. President’s Emergency Plan for AIDS Relief. Available from: http://apps.who.int/iris/bitstream/10665/75357/1/9789241504041_eng.pdf.
  18. Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) Study Group, Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010 May;138(5):1747-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20114048.
  19. Morgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology 2004 Nov;127(5 Suppl 1):S87-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15508108.
  20. 21.0 21.1 Asia-Pacific Working Party on Prevention of Hepatocellular Carcinoma. Prevention of hepatocellular carcinoma in the Asia-Pacific region: consensus statements. J Gastroenterol Hepatol 2010 Apr;25(4):657-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20492323.
  21. Allen KJ, Nisselle AE, Collins VR, Williamson R, Delatycki MB. Asymptomatic individuals at genetic risk of haemochromatosis take appropriate steps to prevent disease related to iron overload. Liver Int 2008 Mar;28(3):363-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18290779.
  22. Larsson SC, Wolk A. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology 2007 May;132(5):1740-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17484871.
  23. Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med 2009 Dec 14;169(22):2053-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20008687.
  24. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012 May;142(6):1264-1273.e1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22537432.
  25. Modi AA, Feld JJ, Park Y, Kleiner DE, Everhart JE, Liang TJ, et al. Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology 2010 Jan;51(1):201-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20034049.

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