Community-based prevention of hepatitis-B-related liver cancer: Australian insights
Monica C Robotin a, Melanie Q Kansil b, Mamta Porwal a, Andrew G Penman a & Jacob George c
a. Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, Sydney, New South Wales, 2011, Australia.
b. Centaurus Partners, Sydney, Australia.
c. University of Sydney School of Medicine, Sydney, Australia.
Correspondence to Monica C Robotin (e-mail: firstname.lastname@example.org).
(Submitted: 15 September 2013 – Revised version received: 14 December 2013 – Accepted: 02 January 2014 – Published online: 04 February 2014.)
Bulletin of the World Health Organization 2014;92:374-379. doi: http://dx.doi.org/10.2471/BLT.13.130344
In May 2010, the Sixty-third World Health Assembly adopted a resolution calling for a comprehensive approach to the prevention and control of all forms of viral hepatitis – which kills over 1 million people each year. Human infection with hepatitis B virus is highly endemic in many Asian countries.1 Such infection is generally acquired early in life and leads to lifelong chronic hepatitis B that has life-threatening complications – such as cirrhosis and hepatocellular cancers (HCCs) – in 25 to 40% of cases.2–4
Over 200 000 Australians are estimated to have chronic hepatitis B5 and liver cancer is now the seventh most common cause of cancer-related death among Australian men.6 In Australia, despite these observations, there is no systematic screening for chronic hepatitis B, even among at-risk groups, and many cases are only detected late, after the onset of complications. In New South Wales – Australia’s most populous state – 46% of HCCs occur among immigrants, particularly those born in countries with endemic hepatitis B.7 Compared with individuals born in Australia, immigrants from China, Indonesia, the Republic of Korea or Viet Nam have a six- to 12-fold greater risk of developing HCCs.7
In addition to vaccination, the public health response to hepatitis B requires screening for the chronic form of the disease, improved access to care and support and improved provider training, education and disease surveillance. To address these challenges as they apply to New South Wales, a local cancer charity – Cancer Council New South Wales – planned and implemented a multi-pronged intervention designed to reduce the incidence of hepatitis-B-related liver cancer among the state’s high-risk migrant communities. The main pillars of this intervention, known as the “B Positive” programme, comprise economic modelling to ascertain the programme’s costs and benefits, educational outreach for both the at-risk migrant communities and their primary-care providers, and establishment of a chronic hepatitis B registry. The registry has been developed to improve not only our understanding of the epidemiology of chronic hepatitis B, but also the follow-up of participants in the B Positive programme. The programme’s key activities and some of the lessons learnt as a result of the programme are summarized below.
The programme was approved by the Institutional Ethics Committee of the Sydney South West Area Health Service and developed in three phases. In Phase 1, economic modelling was used to investigate the feasibility of the programme. The target population was defined, a screening and treatment algorithm for chronic hepatitis B was developed and the types of data to be recorded in the disease registry were determined.
The programme’s target population consists of residents of south-west Sydney born in countries with high prevalences of hepatitis B and who receive primary health care from local general practitioners. However, the programme has also been made available to all local residents with confirmed diagnoses of chronic hepatitis B – irrespective of their countries of birth and modes of disease acquisition. Cases of chronic hepatitis B are identified by general practitioners through medical record checks and opportunistic screening of at-risk patients. Each case is then followed up twice a year. Blood levels of alanine aminotransferase (ALT) and alpha-fetoprotein are determined at each follow-up visit, while levels of hepatitis B virus DNA are measured annually. The programme’s management algorithm is used to categorize the cases as being at high, intermediate or low risk for HCC (Fig. 1). “Low-risk” cases have low viral loads and “normal” levels of ALT; “high-risk” cases have high values for both viral load and ALT; and the cases at “intermediate” risk” have high viral loads but normal levels of ALT. General practitioners are encouraged to refer the high-risk cases for specialist assessment and to continue to follow up the other cases.8
Fig. 1. The B Positive programme’s management algorithm for cases of chronic hepatitis B, Australia, 2007–2014
In Phase 2, the programme’s acceptability to key stakeholders was ascertained. In addition, opportunities for the education of local general practitioners and target communities about hepatitis B testing, prevention and treatment were provided.
In Phase 3 of the programme’s development, an extensive programme redesign was implemented based on consultation with the relevant stakeholders. The monitoring and evaluation tools were refined and the data collected in the case registry were compared against the assumptions made in the economic modelling.
Phase 1 commenced in 2007 with a literature review and a collation of clinical and epidemiological data on which the economic modelling could be based. A Markov economic model was then developed to compare three management strategies: enhanced surveillance for HCC; HCC prevention – in which enhanced HCC surveillance was combined with the optimized management of chronic hepatitis B; and maintenance of the status quo – which was characterized by low levels of treatment uptake for chronic hepatitis B and only opportunistic screening for HCC. For each modelled strategy, case stratification and management were based on age, viral load and ALT level. We modelled a hypothetical cohort of 10 000 Asian-born adults with chronic hepatitis B; all were aged 35 years at enrolment and were followed up for 50 years. The cost of HCC cases, the number of deaths averted and the number of quality-adjusted life years gained over the entire follow-up period were estimated for each strategy. We adopted a health-care funder perspective and discounted all future costs and health outcomes by 5% per year.
Only one of the three strategies modelled – HCC prevention – appeared to be cost-effective and able to deliver substantial health benefits. In the model, this strategy reduced cases of cirrhosis, HCC diagnoses and hepatitis-B-related deaths over the 50 years of follow-up by 52%, 47% and 56%, respectively, at an estimated cost of 12 956 Australian dollars for each quality-adjusted life year gained.8 As a consequence of this modelling work, the B Positive programme used the HCC-prevention approach.
The programme has only led to a slight increase in the workloads of the general practitioners who serve the target communities. It is expected, however, to substantially increase the local demand for specialist services needed in the management of HCC,9 even though most cases of chronic hepatitis B enrolled in the programme can be managed at the primary-care level. Only 8 to 25% of cases – the exact proportion depending on the guidelines that are followed for treatment initiation – require antiviral treatment.10 However, in the economic modelling, the cost of antiviral drugs accounted for most (54–76%) of the estimated total cost of the programme.10 The economic modelling showed that the estimated costs attributed to surveillance for chronic hepatitis B (4–30% of the programme’s total cost) and HCC screening and surveillance (5–9%) were relatively small.10
All local general practitioners were invited to free “continuing medical education” seminars on hepatitis B and provided with tailored educational resources. A quarter of the local general practitioners attended at least one seminar in the 18 months following the programme’s launch. Approximately 2500 members of the target communities attended at least one of the hepatitis-B-themed events run by the programme, with educational talks delivered in Cantonese, English, Mandarin and Vietnamese. At the same events, fact sheets on hepatitis B – in Arabic, Chinese, English, Indonesian, Korean and Vietnamese – were also distributed. Low programme uptake in the first 18 months – when only six general practitioners and 32 patients were enrolled in the case registry – prompted a wide stakeholder consultation to ascertain the reasons for the low enrolment and to seek suggestions for the redesign and improvement of the programme.
Semi-structured interviews with 88% of the general practitioners who attended the seminars helped to identify some options to improve programme enrolments. The interviewees suggested reducing the number of data fields in the registry, offering enrolment via the World Wide Web and providing administrative support and a small financial incentive to the primary-care practices of participating general practitioners. Other suggestions for improving the programme came from community health workers and Vietnamese- and Cantonese-speaking residents of south-western Sydney.
The B Positive programme was re-launched in 2011, with an improved patient reminder and recall system, enhanced practitioner support and the introduction of incentive payments for general practitioners and a nurse educator to facilitate case identification and strengthen linkages with the tertiary sector. The minimum number of data fields to be completed for each case recorded in the case registry was reduced from 36 to 14 and provisions were made for online enrolment. The algorithm used for the management of chronic hepatitis B was simplified, in line with recommendations of the Gastroenterological Society of Australia.11 The continuing medical education scheme for general practitioners has recently been expanded and seminars are now offered more frequently, with funding and additional resources provided by the Australasian Society for HIV Medicine.
The programme’s relaunch also entailed revisions to our interventions for improving community engagement. We consulted widely to ensure that our community-level educational activities were culturally sensitive and adequately tailored to the target communities. We also established collaborations with key community-based organizations, local councils and schools. Messages designed to improve screening for hepatitis B are now widely disseminated at community meetings, festivals and fairs and marketed through “ethnic” newspapers, newsletters and radio programmes. Differential messaging is used for specific audiences – such as students attending English-language classes, school students, the elderly and recently arrived migrants – and we provide education on hepatitis B in an increasing number of languages, including Assyrian, Cambodian, Khmer and Laotian. New hepatitis-related resources have been developed, tested and translated, including a travelling hepatitis library, posters detailing hepatitis myths and misconceptions and a cartoon video. With the support and collaboration of local immigrants from Viet Nam, we produced a soap-opera-style film in Vietnamese. The actors in this film were local residents and important messages about hepatitis B were woven into the storyline. Although this film has only been shown in two cinemas, it is envisaged that it will be distributed more widely and, perhaps, broadcast on at least one local television channel. Local high-school students learn about hepatitis B as they are taught about film animation and they convey messages about hepatitis B prevention to their peers, families and communities.
Over the last 12 months, the number of individuals enrolled in the hepatitis registry has increased substantially. At the time of writing, more than 1200 cases – approximately 15% of the entire target population – are enrolled and being followed up by more than 50 local general practitioners.
The recent effectiveness of the B Positive programme was highlighted by the results of a nationwide survey on the uptake of treatment by those with cases of chronic hepatitis B in Australia. The percentage of such cases in south-west Sydney who were receiving treatment (7%) was found to be higher than that in any other surveyed area and double the nationalaverage.12
The main lessons learnt from the B Positive programme (Box 1) indicate that a public health intervention to tackle chronic hepatitis B and its complications can be feasible, acceptable to the target communities and effectively delivered by trained general practitioners. The initial problem of low programme uptake was corrected by a wide consultation and a substantial redesign of the programme – highlighting the critical role of ongoing monitoring and stakeholder consultations in the success of this and similar programmes.
Box 1. Summary of main lessons learnt
- As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, the facilitation of treatment access is a rational, appropriate and cost-effective option in the management of the disease.
- The identification and accurate staging of cases of chronic hepatitis B and the judicious use of antiviral medications are predicated upon an informed and educated health workforce.
- Programmes for the population-based management of chronic hepatitis B should not be delayed until antiviral drugs become cheaper, as establishing community trust in such programmes is likely to be a lengthy and involved process.
The interventions implemented in the B Positive programme are similar to those followed in similar large-scale, community-based programmes in New Zealand13 and the United States of America.14,15 The B Positive programme has been seeking to reduce hepatitis-B-related health disparities in migrant populations through community-based screening, linkage to care and increasing community-level awareness of hepatitis B and participation in disease surveillance. Meaningful community engagement has played a critical role in the programme’s success. Without such engagement and adequate input from the “recipient” communities, programme uptake would probably have been too poor to have had a significant impact on any hepatitis-B-related health problem. Whitehead identified a spectrum of community-based interventions – ranging from those where the community is the driver and funding agent to those controlled by external agencies – in which the establishment of equitable and mutually rewarding partnerships represented the “ideal” scenario.16 The original B Positive programme was launched with limited community involvement, with the target communities being the programme’s recipients but having little opportunity to contribute to the programme’s design. Only after the programme’s goals were clearly communicated and the scope of community consultation was widened did the programme’s aims become relevant to the target communities – resulting in increased programme uptake.
As far as we are aware, B Positive is the only population-based programme for chronic hepatitis B mitigation guided by economic modelling and using a case registry to support patient follow-up and linkage to treatment. In the absence of systematic surveillance for chronic hepatitis B in Australia, data collected in our case registry are helping to characterize the clinical features, staging and treatment needs of people with the disease.
In chronic hepatitis B, the high cost of antiviral therapy currently makes the treatment of all cases identified in population-based screenings unaffordable in many countries. However, it appears that only a relatively small proportion of those diagnosed with the disease require antiviral treatment and that cases needing antiviral therapy can be effectively identified using a relatively simple screening and follow-up algorithm. The data collected in the B Positive programme indicate that, among high-risk groups, such a system can be fairly readily implemented at primary-care level, at an acceptable cost. We envisage that community-based screening for chronic hepatitis B and community-based treatment will soon become a reality, even in resource-limited settings.
As the building of adequate community trust requires careful planning and much lead time, it appears unreasonable to defer public health action against chronic hepatitis B until antiviral treatment becomes less costly. Today’s challenge is to move beyond demonstration projects to full-scale implementation. This is reminiscent of the state of affairs seen in the management of human immunodeficiency virus (HIV) a decade ago, as summarized by Moatti et al.: “Scaling up access to antiretroviral drugs (ARVs) for HIV-infected adults and children in developing countries can no longer be refused for medical or economic reasons, or on the grounds of inequality, lack of infrastructure, risk of viral resistance or alternative priorities. Access to ARVs is an appropriate, rational and cost-effective investment choice in developing countries.”17
We gratefully acknowledge the contribution of the B Positive team; the input of the members of the B Positive Steering Committee and the support of local general practitioners and the Division of General Practice. We thank our community-based partners and people affected by hepatitis B, whose support made the programme possible. MCR has a dual appointment with the University of Sydney School of Medicine, Sydney, Australia. JG has a dual appointment with the Storr Liver Unit, Millennium Institute, Westmead, Australia.
The B Positive programme is funded by Cancer Council New South Wales. Since June 2012, a nurse-educator involved in the programme has been funded by the New South Wales Department of Health. JG is funded by the Sydney Medical Foundation of the University of Sydney and by grants from the National Health and Medical Research Council of Australia (Project grant 1047417 and programme grant 1053206), the Cancer Council New South Wales (Strategic Research Partnership grant SRP 08-03) and the New South Wales Cancer Institute (grant 11/TRC/1-6).
- Nguyen T, Thompson AJV, Bowden S, Croagh C, Bell S, Desmond PV, et al., et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010; 52: 508-13 http://dx.doi.org/10.1016/j.jhep.2010.01.007 pmid: 20206400.
- Ganem D, Prince AM. Hepatitis B virus infection – natural history and clinical consequences. N Engl J Med 2004; 350: 1118-29 http://dx.doi.org/10.1056/NEJMra031087 pmid: 15014185.
- Villeneuve JP. The natural history of chronic hepatitis B virus infection. J Clin Virol 2005; 34: S139-42 http://dx.doi.org/10.1016/S1386-6532(05)80024-1 pmid: 16461215.
- Yuen M-F. Revisiting the natural history of chronic hepatitis B: impact of new concepts on clinical management. J Gastroenterol Hepatol 2007; 22: 973-6 http://dx.doi.org/10.1111/j.1440-1746.2007.04938.x pmid: 17489961.
- 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: 416-22 http://dx.doi.org/10.1111/1753-6405.12049 pmid: 24090323.
- Cancer in Australia: an overview, 2012. Canberra: Australian Institute of Health and Welfare; 2012. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129542353 [accessed 17 January 2014].
- Supramaniam R, O’Connell DL, Tracey E, Sitas F. Cancer incidence in New South Wales migrants 1991 to 2001. Sydney: The Cancer Council; 2006.
- Robotin MC, Kansil M, Howard K, George J, Tipper S, Dore GJ, et al., et al. Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening. J Hepatol 2009; 50: 990-8 http://dx.doi.org/10.1016/j.jhep.2008.12.022 pmid: 19303657.
- Ratnam D, Dev A, Nguyen T, Sundararajan V, Harley H, Cheng W, et al., et al. Efficacy and tolerability of pegylated interferon-α-2a in chronic hepatitis B: a multicenter clinical experience. J Gastroenterol Hepatol 2012; 27: 1447-53 http://dx.doi.org/10.1111/j.1440-1746.2011.07051.x pmid: 22168789.
- Robotin M, Patton Y, Kansil M, Penman A, George J. Cost of treating chronic hepatitis B: comparison of current treatment guidelines. World J Gastroenterol 2012; 18: 6106-13 http://dx.doi.org/10.3748/wjg.v18.i42.6106 pmid: 23155339.
- Australian and New Zealand chronic hepatitis B (CHB) recommendations. Clinical update. Mulgrave: Gastroenterological Society of Australia; 2009. Available from: http://www.gesa.org.au/files/editor_upload/File/Professional/CHB.pdf [accessed 17 January 2014].
- Australasian Society for HIV Medicine [Internet]. Medicare locals planning project. Surry Hills: 2012. Available from: http://www.ashm.org.au/default2.asp?active_page_id=510 [accessed 17 January 2014].
- Herman A, Bullen C, Finau S, Ofanoa M. Mobilising Pacific people for health: insights from a hepatitis B screening programme in Auckland, New Zealand. Pac Health Dialog 2006; 13: 9-15 pmid: 18181385.
- Gish RG, Cooper SL. Hepatitis B in the Greater San Francisco Bay Area: an integrated programme to respond to a diverse local epidemic. J Viral Hepat 2011; 18: e40-51 http://dx.doi.org/10.1111/j.1365-2893.2010.01382.x pmid: 21143342.
- Pollack H, Wang S, Wyatt L, Peng CH, Wan K, Trinh-Shevrin C, et al., et al. A comprehensive screening and treatment model for reducing disparities in hepatitis B. Health Aff (Millwood) 2011; 30: 1974-83 http://dx.doi.org/10.1377/hlthaff.2011.0700 pmid: 21976342.
- Whitehead T. Community based interventions, definitions and types. In: University of Maryland, editor. The cultural ecology of health and change (CEHC). Maryland: University of Maryland; 2002.
- Moatti JP, N’Doye I, Hammer SM, Hale P, Kazatchkine M. Antiretroviral treatment for HIV infection in developing countries: an attainable new paradigm. Nat Med 2003; 9: 1449-52 http://dx.doi.org/10.1038/nm1203-1449 pmid: 14647513.