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Primary liver cancer and chronic hepatitis B Primary liver cancer is now one of the top ten causes of cancer death in Australia. Median survival from the most common form of liver cancer, hepatocellular carcinoma (HCC), is just five months. Chronic hepatitis B (CHB) is the most common cause of liver cancer worldwide.1 Almost 800,000 Australians die from hepatitis B infection every year.2 Recent migration from countries with a high prevalence of hepatitis B has increased the local incidence of CHB and HCC3, and screening people born in endemic countries is effective in identifying risk and linking to care.4 A large proportion of HCC is preventable through vaccination against hepatitis B. Chronic hepatitis B prevalence in Australia, by risk group9 HBsAg prevalence in risk group (%) Group 2.4 (average) People born in high or intermediate-prevalence countries Hepatitis B transmission Hepatitis B can be transmitted: Proportion of CHB in Australia (%) •vertically, from mother to child. 3.6 (Asia and Pacific regions) 2.7 (Africa/Middle East) 56 1.0 (Europe) •horizontally, through: - close household contact with an infected person - sexual contact with an infected person - skin piercing - medical procedures - open wounds from an infected individual. 5 At a global level, mother to child transmission is responsible for the largest number of infections.6 80-90 per cent of infections contracted before one year of age lead to chronic infection, compared with 30-50 per cent of childhood infections and less than 5 per cent of infections contracted in adulthood.7 In countries where CHB infection is uncommon in the general population, most infections are acquired in adulthood, are self-limiting and result in clearing the virus from the blood and liver and long-lasting immunity to re-infection.8 A small proportion of adults who become infected (< 5%) fail to clear the infection and may have ongoing viral replication.8 Working together to lessen the impact of cancer Aboriginal and Torres Strait Islander people 3.7 9 People who inject drugs 4 6 Men who have sex with men 3 4 Non-Aboriginal Australianborn individuals* 0.3 19 Other or not stated 1.0 6 *excluding those belonging to the other priority populations listed above; CHB, chronic hepatitis B; HBsAg, hepatitis B surface antigen Additional reading Further references to hepatitis B and liver cancer are available in B Positive. All you wanted to know about hepatitis B. A guide for primary care providers.10 Fact sheet Primary liver cancer and chronic hepatitis B Symptoms of hepatitis B infection Hepatitis B treatment The acute infection phase is commonly asymptomatic, but some people experience: Acute hepatitis B generally requires supportive care only. •jaundice •dark urine •extreme fatigue •nausea •vomiting and abdominal pain for a period of several weeks. Acute liver failure occurs rarely, but can lead to death.5 Hepatitis B diagnosis The hallmark of hepatitis B infection is the detection of the hepatitis B surface antigen – HBsAg in the serum. Acute hepatitis B virus (HBV) infection is characterised by the presence of HBsAg and immunoglobulin M (IgM) antibody to the core antigen, HBcAg. During the initial phase of infection, patients are also seropositive for hepatitis B e antigen (HBeAg). HBeAg is usually a marker of high levels of viral replication. The presence of HBeAg indicates that the blood and body fluids of the infected individual are highly contagious. Chronic hepatitis B infection is characterised by the persistence of HBsAg for at least six months (with or without concurrent HBeAg). Persistence of HBsAg is the principal marker of risk for developing chronic liver disease and HCC later in life.5 See Figure 1. Ascertaining the extent of liver fibrosis is critical for decisionmaking in patients with chronic liver disease. Transient elastography (TE, or FibroScan) has replaced liver biopsy in the clinical armamentarium for the diagnosis and assessment of liver fibrosis.11 Figure 1: Natural history of chronic hepatitis B infection The Australasian Society of HIV Medicine runs courses for general practitioners wishing to become hepatitis B prescribers. Prevention of hepatitis B and liver cancer A comprehensive public health response to hepatitis B needs to integrate primary, secondary and tertiary prevention into a coordinated response. Primary prevention of hepatitis B and liver cancer Hepatitis B vaccination and reduced exposure to the virus (e.g. through screening blood donors and safe injection techniques) are effective approaches to primary prevention. It is recommended that all newborns receive the first dose of hepatitis B vaccine within 24 hours of birth, followed by a further three doses in infancy, at 2, 4 and 6 months of age. Adolescents not vaccinated as children, and adults at risk of exposure to HBV or at risk of severe disease, should also be targeted for vaccination. For further details, see the Australian Immunisation Handbook Secondary prevention: hepatitis B and management As antiviral treatment can significantly reduce the incidence of HCC, screening and improved management of chronic viral hepatitis are integral components of HCC prevention. N further No progression HCC Normal liver Chronic hepatitis B infection may require treatment with antiviral agents to slow the progression of cirrhosis, reduce the incidence of liver cancer and improve long-term survival.5 Current treatments are rarely curative, but suppress replication of the virus, so antiviral treatments are long-term (typically lifelong). Chronic hepatitis B Cirrhosis End stage liver disease Working together to lessen the impact of cancer The goals of therapy in HBV-infected patients include reducing the level of viraemia and a correction of liver dysfunction, with treatment indicated in people with chronic hepatitis B infection who have elevated ALT levels and elevated viral loads.8 Adequate control of chronic hepatitis B leads to a reduction in the risk of fibrosis and cirrhosis, HCC development and end stage liver disease. Markers of successful therapy include the clearance of HBeAg, seroconversion to anti-HBe antibodies, and a reduction in the circulating viral load.8 Fact sheet Primary liver cancer and chronic hepatitis B Tertiary prevention: screening for HCC Liver ultrasound (US) is the test of choice for HCC screening, and combining this with serum alpha-fetoprotein (AFP) measurement increases HCC detection by a further 6-8 per cent.12 Six monthly follow-up is required as a negative screening result cannot reliably exclude the presence of HCC.13 Current management guidelines recommend that HCC surveillance should be offered to people with cirrhosis, or other HCC risk factors, including: •Asian men over the age of 40 •Asian women over the age of 50 •African people older than 20 years of age •People with a family history of primary liver cancer.14,15 Population-level models of hepatitis B screening and treatment Preventing HCC is contingent on educating and engaging the affected population to become active participants in their care. South-West Sydney has the highest burden of both chronic hepatitis B16 and HCC17 in Australia. B Positive is a local program based in South-West Sydney that uses a CHB disease registry to support evidence-based and timely patient follow up and referrals. With the help of local general practitioners, 21% of enrolled participants are on antivirals and treatment uptake is almost four times the national average.18 References 1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11(2):97-107. 11.Chon YE, Choi EH, Song KJ, Park JY, Kim do Y, Han KH, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One 2012;7(9):e44930. 2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2095-128. 12.De Masi S, Tosti ME, Mele A. Screening for hepatocellular carcinoma. Dig Liver Dis 2005;37(4):260-8. 3. MacLachlan J, Allard N, Towell V, Cowie B. The burden of chronic hepatitis B virus infection in Australia, 2011. Australian and New Zealand Journal of Public Health 2013:online 14.Sherman M. Pathogenesis and screening for hepatocellular carcinoma. Clin Liver Dis 2004;8(2):419-43, viii. 4. Thomson MD, Hoffman-Goetz L. Cancer information comprehension by Englishas-a-second-language immigrant women. J Health Commun 2011;16(1):17-33. 5. World Health Organization. Hepatitis B fact sheet no 204. Geneva: WHO, 2012. 13.Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005;25(2):143-54. 15.Gastroenterological Society of Australia and Digestive Health Foundation. Australian and New Zealand chronic hepatitis B (CHB) recommendations. Clinical update In: Foundation DH, editor, 2010. 6. Custer B, Sullivan SD, Hazlet TK, Iloeje U, Veenstra DL, Kowdley KV. Global epidemiology of hepatitis B virus. J Clin Gastroenterol 2004;38(10 Suppl 3):S158-68. 16.MacLachlan J, Cowie B. Hepatitis B Mapping Project: Estimates of chronic hepatitis B prevalence and cultural and linguistic diversity by Medicare Local, 2011 – National Report. In: ASHM, editor. Sydney: Australasian Society for HIV Medicine, 2013 40. 7. World Health Organization (WHO). Immunization surveillance, assessment and monitoring.: WHO. 17.Alam N, Chen W, Baker D, Bishop J. Liver Cancer in New South Wales. In: Cancer Institute NSW, editor. Sydney: Cancer Institute NSW, 2009. 8. Ganem D, Prince AM. Hepatitis B Virus Infection — Natural History and Clinical Consequences. New England Journal of Medicine 2004;350(11):1118-29. 18.MacLachlan J, Cowie B. Hepatitis B mapping project: Estimates of chronic hepatitis B diagnosis, monitoring and treatment by Medicare Local. National Report 2012/13 In: Australasian Society for HIV Medicine, editor. Hepatitis B mapping project Sydney Australasian Society for HIV Medicine (ASHM) and Victorian Infectious Diseases Reference Laboratory (VIDRL), 2015. 9. MacLachlan JH, Allard N, Towell V, Cowie BC. The burden of chronic hepatitis B virus infection in Australia, 2011. Aust N Z J Public Health 2013;37(5):416-22. 10.Matthews G, Robotin M, Allard N, editors. B Positive-all you wanted to know about hepatitis B: a guide for primary care providers. second ed. Sydney: ASHM, 2014. Working together to lessen the impact of cancer Cancer Institute NSW PO Box 825, Alexandria, NSW 1435 t +61 (0)2 8374 5600 f +61 (0)2 8374 3600 e [email protected] www.cancerinstitute.org.au © Cancer Institute NSW 2015. Created May 2015. While every effort has been made to provide accurate information, this document is not intended as a substitute for medical advice. Contact your doctor if you have any concerns. See www.eviq.org.au for our full disclaimer and any updates.