In order to halt the growing burden of liver cancer a comprehensive national liver cancer control strategy needs to be developed and implemented. A strategy would build on and strengthen existing frameworks in hepatitis B virus (HBV) and hepatitis C virus (HCV) prevention and control, primary care, hepatocellular carcinoma Optimal Care Pathway and include routine reporting and evaluation. Prioritising ‘best buy’ interventions to reduce liver cancer incidence and mortality in the next five- and 10-year periods is an urgent area for government action.
In the absence of a national liver cancer control strategy, Cancer Council recommends optimising uptake of HBV vaccination in high-risk populations, improving access to diagnosis and treatment for individuals with HBV and HCV and implementing a liver cancer surveillance program in high risk individuals.
Develop and implement national liver cancer control strategy
Increase awareness of risk factors for liver cancer
Low awareness and understanding of viral hepatitis are associated with increased risk of transmission (Balfour 2009), lower likelihood of vaccination, underutilisation of treatment options and lower likelihood of cancer screening.
As such, increasing awareness of viral and non-viral risk factors associated with liver cancer is essential to reduce the future burden of liver cancer in Australia. An adequately funded public education campaign targeted at high-risk groups is required to increase awareness of risk factors for liver cancer.
Optimise hepatitis B vaccine coverage in high-risk populations
Chronic HBV infection is considered endemic in Aboriginal and Torres Strait Islander communities due to poor vaccine uptake and incomplete vaccination. Low vaccination coverage in populations at risk has been attributed to a lack of awareness, failure by health professionals to identify and offer vaccinations to at-risk persons, the cost of accessing the HBV vaccine (the vaccine is free in some jurisdictions, but there is often a consultation fee) and failure to complete the full course of three doses.
In Australia, the groups at highest risk of liver cancer due to chronic hepatitis also face the greatest barriers to accessing services. Aboriginal and Torres Strait Islander and some migrant groups face barriers related to cultural, linguistic and/or religious differences, poverty, distance and low literacy. As such, strategies to increase vaccination should be sensitive to culture, religion and in a language that is understood by the target population. Targeted education strategies are key to improving awareness of the benefits of the vaccination for high-risk populations. Better awareness about the benefits of vaccination would likely encourage individuals to seek advice from their health care practitioners. The use of bilingual health promotion officers may be pivotal in helping high-risk populations understand the benefits of vaccinations and the importance of completing a full course. Aboriginal Health Workers may help promote the benefits of completing a full course for Aboriginal and Torres Strait Islander populations. Given the limited evidence of effective strategies targeting priority populations, further research and evaluation to build and share knowledge is recommended.
Primary health care practitioners (especially general practitioners) have a central role in identifying and offering vaccinations to high-risk individuals and should be supported to do this. Options include providing incentives to general practitioners for vaccinating high-risk individuals.
Improve access to treatment for individuals with viral hepatitis B and C
It is estimated that 39% of people with chronic HBV and 20% of people with chronic HCV remain undiagnosed. Only a small proportion of those who have been diagnosed with chronic hepatitis have received appropriate treatment.
Targeted education strategies are also essential to encouraging individuals infected with viral hepatitis to access treatment. Australian modelling has shown that antiviral treatment for chronic HBV is a highly cost-effective way to prevent liver cancer. A pilot study conducted in NSW demonstrated that general practitioners who were supported to test and manage chronic HBV increased their patients’ uptake of antiviral treatment to rates which were the highest in the country.
One option for increasing access to treatment is to make therapies available outside tertiary centres, that is through primary care and community-based health centres, methadone clinics and other settings. Shifting treatment and care to primary care settings has further potential to increase treatment and follow-up care; especially in rural areas and in a number of high-risk groups. Targeted education and awareness strategies are also essential to encouraging individuals infected with viral hepatitis to access treatment and care.
Improved therapies with lower toxicity and shorter treatment regimens have revolutionised HCV treatment in Australia, with more people having been treated since March 2016 than in the two decades prior. There is a need to raise awareness of the impact of co-factors such as obesity, and alcohol consumption, and the importance of making healthy lifestyle choices to prevent progression to liver cancer, especially among people infected with viral hepatitis.
Implement a liver cancer surveillance program
The key to improving survival for liver cancer is surveillance of high-risk populations allowing for early diagnosis and treatment. Australia currently does not have evidence-based clinical practice guidelines for the prevention and early detection of liver cancer; nor a formal liver cancer surveillance program. The Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine recommends that patients with chronic HBV who have cirrhosis, and other patients with chronic HBV at high risk (determined by family history, ethnicity, age, and sex) be screened with ultrasonography with or without alpha-fetoprotein (AFP) testing every 6 months. Biannual ultrasound screening is recommended for patients with HCV who have cirrhosis. The American Association for the Study of Liver Diseases have the same recommendations and with the Infectious Disease Society of America, has made additional recommendations for screening patients with HCV and advanced liver fibrosis. Similarly, the European Society for Medical Oncology suggests using the same strategy to screen patients who have chronic HBV and cirrhosis or other additional risk factors or have HCV with bridging fibrosis as they are at a higher risk of developing liver cancer than the general population.
Large-scale studies show that surveillance is correlated with significantly better survival outcomes when compared with no surveillance for patients with chronic hepatitis and patients with cirrhosis . Among patients with cirrhosis, surveillance also improves likelihood of being diagnosed at an earlier stage and undergoing curative treatment.
Surveillance for liver cancer is the accepted standard of care internationally and in Australia for people with chronic HBV and HCV in at-risk groups. Japan has demonstrated a successful model of national liver cancer surveillance which has drastically improved survival rates. National surveillance for liver cancer has resulted in high detection rates of early stage disease (62% in Japan compared to 30% in Western countries) . Liver cancer surveillance in Japan is supported by registries and public education campaigns to increase awareness among high-risk groups.
The number of people requiring liver cancer surveillance in Australia is unknown, however, a population-based study estimates show that around 79% of participants with chronic HBV in a targeted geographic area require liver cancer surveillance.
A liver cancer surveillance program could monitor those at highest risk and allow for early diagnosis and treatment. Population-based registries and targeted communications supporting a surveillance program are required for the greatest benefit. Targeted media campaigns should focus on increasing awareness of risk factors for viral hepatitis in high risk groups and encourage them to see their general practitioner. Priority groups such as people born overseas in high-prevalence areas, and Aboriginal and Torres Strait Islander people would benefit from a liver cancer surveillance program. The implementation of a national surveillance program is an urgent priority area for action in order to address increasing numbers of liver cancer deaths.
Surveillance strategies for patients at high-risk of liver cancer, caused by non-viral factors, are less clear. NAFLD-related cirrhosis is a risk factor for liver cancer; however, liver cancer has also been observed in NAFLD patients in the absence of cirrhosis, but at lower rates. As the incidence of NAFLD-related liver cancer is predicted to rise, along with obesity rates, optimal surveillance strategies should be investigated to reduce cancer burden.
- Soto-Salgado M, Suárez E, Ortiz AP, Adrovet S, Marrero E, Meléndez M, et al. Knowledge of viral hepatitis among Puerto Rican adults: implications for prevention. J Community Health 2011 Aug;36(4):565-73 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21125319.
- Treloar C, Hull P, Bryant J, Hopwood M, Grebely J, Lavis Y. Factors associated with hepatitis C knowledge among a sample of treatment naive people who inject drugs. Drug Alcohol Depend 2011 Jul 1;116(1-3):52-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21194852.
- Nguyen GT, Bellamy SL. Cancer information seeking preferences and experiences: disparities between Asian Americans and Whites in the Health Information National Trends Survey (HINTS). J Health Commun 2006;11 Suppl 1:173-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16641082.
- MacLachlan J, Thomas L, Cowie B. Viral Hepatitis mapping project, geographic diversity in chronic Hepatitis B and C prevalence, management and treatment: National Report 2017. Darlinghurst, NSW: Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine; 2019 [cited 2020 Apr 29] Available from: https://ashm.org.au/products/product/Viral-Hepatitis-Mapping-Project-2017.
- Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: Annual surveillance report. Sydney: University of New South Wales; 2018. Sponsored by Department of Health and Ageing. Available from: https://kirby.unsw.edu.au/sites/default/files/kirby/report/KI_Annual-Surveillance-Report-2018.pdf.
- Australasian Society for HIV Medicine. Hepatitis B related hepatocellular carcinoma. B positive: Hepatitis B for primary care. [homepage on the internet] Sydney: ASHM; 2014 [cited 2020 Apr 29]. Available from: https://www.ashm.org.au/products/product/1976963310.
- Robotin MC, Kansil M, Howard K, George J, Tipper S, Dore GJ, et al. Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening. J Hepatol 2009 May;50(5):990-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19303657.
- Robotin MC, Masgoret X, Porwal M, Goldsbury D, Khoo C, George J. Using a chronic hepatitis B Registry to support population-level liver cancer prevention in Sydney, Australia. Clin Epidemiol 2018;10:41-49 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29339926.
- Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of Hepatitis C virus infection: A consensus statement (September 2018). Melbourne: Gastroenterological Society of Australia; 2018 [cited 2020 Apr 29] Available from: https://www.asid.net.au/documents/item/1208.
- Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018 Apr;67(4):1560-1599 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29405329.
- Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018 Jan;67(1):358-380 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28130846.
- American Association for the Study of Liver Disease and the Infectious Diseases Society of America. Hepatitis C Guidance: AASLD-IDSA recommendations for testing, managing and treating adults infected with Hepatitis C virus. Hepatology 2015 [cited 2020 Apr 29];62(3) Available from: https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.27950.
- Vogel A, Cervantes A, Chau I, Daniele B, Llovet J, Meyer T, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018 Oct 1;29(Suppl 4):iv238-iv255 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30285213.
- Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004 Jul;130(7):417-22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15042359.
- Tanaka H, Nouso K, Kobashi H, Kobayashi Y, Nakamura S, Miyake Y, et al. Surveillance of hepatocellular carcinoma in patients with hepatitis C virus infection may improve patient survival. Liver Int 2006 Jun;26(5):543-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16761998.
- Trevisani F, De Notariis S, Rapaccini G, et al. Semiannual and Annual Surveillance of Cirrhotic Patients for Hepatocellular Carcinoma: Effects on Cancer Stage and Patient Survival (Italian Experience). Am J Gastroenterol 2002 [cited 2020 Apr 30];97(3): 734-744 Available from: https://pubmed.ncbi.nlm.nih.gov/11922571/.
- Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 2014 Apr;11(4):e1001624 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24691105.
- Kudo M. Japan's Successful Model of Nationwide Hepatocellular Carcinoma Surveillance Highlighting the Urgent Need for Global Surveillance. Liver Cancer 2012 Nov;1(3-4):141-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24159578.
- Paradis V, Zalinski S, Chelbi E, Guedj N, Degos F, Vilgrain V, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009 Mar;49(3):851-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19115377.
- Leung C, Yeoh SW, Patrick D, Ket S, Marion K, Gow P, et al. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease. World J Gastroenterol 2015 Jan 28;21(4):1189-96 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25632192.
- Perumpail RB, Wong RJ, Ahmed A, Harrison SA. Hepatocellular Carcinoma in the Setting of Non-cirrhotic Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome: US Experience. Dig Dis Sci 2015 Oct;60(10):3142-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26250831.
- Issa D, Alkhouri N. Nonalcoholic fatty liver disease and hepatocellular carcinoma: new insights on presentation and natural history. Hepatobiliary Surg Nutr 2017 Dec;6(6):401-403 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29312975.