Epidemiological modelling to address burden of hepatitis B in resource poor settings: Impact & cost-effectiveness of intervention strategies

Hepatitis B (HBV) is a virus which can cause liver damage and liver cancer if left untreated. In the developing world, in particular in sub-Saharan Africa (SSA), although up to 15% of the population are estimated to be chronically infected with the virus, free treatment is not universally available. Tenofovir is a safe & effective drug which is used to treat HBV in the developed world and is now is also routinely available for use in HIV treatment programmes in developing countries.

A recent 5 year research platform called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa), funded by the EU, has been set up in West Africa to screen the population for hepatitis B carriers (who often have no symptoms), and offer treatment if needed, with the main aim of reducing liver cancer and death due to HBV, in West Africa. It is also looking at various epidemiological, biological and genetic factors involved in the development of liver cancer in the West African population.

Since HBV, is often, a slowly progressing chronic disease, the actual impact of interventions to reduce HBV morbidity and mortality can takes decades to assess by following clinical observation cohorts. Epidemiological models are therefore, a useful tool in public health to use current knowledge of how a disease progresses, to project the likely impact of interventions on controlling the disease and its related mortality. Delaying interventions until full outcomes are available can miss a vital opportunity to help those already afflicted by the disease. Although epidemiological models for HBV exist, they mostly apply to high/middle income countries, countries with lower prevalence of HBV, have too simplistic model structures and don't evaluate the effect of community based screening. Therefore, their use in projecting disease control strategies in SSA, is limited.

I aim to develop a model for HBV, specifically applicable to resource-poor countries and use this model, to predict the impact of various interventions including screening & treatment programmes. The hypothesis is that early intervention should reduce primary liver cancer and death due to HBV. Initial methods include reviewing published literature on the natural history of HBV and the probabilities of developing different stages of the disease. Computer based programming techniques will be employed to generate disease transmission models. Limited published data exists on how the Hepatitis B virus behaves in the African population. Therefore, data derived as part of the PROLIFICA programme, can be inputted to make this model applicable to the West African population.

In countries, where budgets are limited, it is not sufficient to just demonstrate that clinical interventions are effective against a disease, but that they also represent value for money. I therefore propose to explore whether this strategy is cost effective. Again, analyses exist, but mainly in high-income countries, and vary in medications used. Using locally applicable data on costs, both to the health care provider and to the households, these economic analyses will provide key information for health policy makers. As liver cancer due to HBV, in West Africa, often occurs in males in their 30s-40s, loss to the economy is potentially underestimated by traditional CE analyses, which are routinely used in the western world.

Results from this research, will be important in informing health policy makers, like WHO, and funding agencies, like the Global Fund, into the immense public health importance of providing treatment (like that offered in PROLIFICA) free for patients suffering from HBV, in the developing world, to prevent premature death and suffering due to HBV. While initially focusing on HBV in West Africa, the research will develop a model that can be adjusted to be applicable in other countries with varying prevalence of hepatitis B and costs.

BACKGROUND: Despite childhood vaccination programmes, Hepatitis B virus (HBV) is still widespread in resource-poor settings (eg. in The Gambia 15-20% of adults are estimated to be chronically infected with HBV). Evidence in high-income countries shows that HBV treatment is effective in reducing HCC, as well as, cost effective (CE). However, there has been minimal action or research into developing similar intervention programmes in sub-Saharan Africa. Disease modelling & CE analyses, demonstrating the likely significant public health impact, may help change this lack of commitment.

AIMS & OBJECTIVES: Generation of epidemiological models to address the burden of hepatitis B and hepatocellular carcinoma in resource poor settings: Impact and cost-effectiveness of screening & treatment programmes.

METHODOLOGY: The main data source for Africa specific epidemiological and cost data will be the PROLIFICA programme, a 5 year, EU funded, community screening and treatment platform & HCC case control platform in West Africa. After systematic literature review into the natural history of HBV, the development of HBV markov state transmission model, using these transmission parameters, will be developed. Computational programming will use the force of infection, chronic carriage and age dependent models to model HBV related morbidity and mortality and the impact of screening and treatment. Inputting parameters generated from PROLIFICA, will allow outcome predictions specific to West Africa, with potential future applicability, once validated, to other sub-Saharan countries. CE of this hepatitis B screening and treatment programmes from a provider, as well as a societal perspective, will be evaluated by collecting both health and cost data, from the PROLIFICA programme, health facilities in the Gambia and household questionnaires. Embedding these results into the disease burden model will output cost per episode and DALYs averted by screening and treatment.

1. Academia
In addition to the specific benefits within academia, outlined above, I hope that through my research I will foster a culture of closer collaboration and understanding between clinicians, modellers and health policy makers, in answering fundamental questions in infectious disease control.

2. Society - abroad
The beneficiaries of this research hopefully will, primarily, be the thousands of people suffering from chronic hepatitis B in the developing world. With the output of my research, I propose, that a documented benefit will be recorded to help with advocacy for access, drug availability and implementation of further hepatitis B screening and treatment platforms in resource poor settings. With the eventual long-term aim of potential eradication of hepatitis B.

3. Society - UK
In the UK, especially in London, the majority of chronic hepatitis B infection, is seen among the immigrant population. The models developed during my research, can also be applied to evaluate the impact and cost effectiveness of screening programmes among immigrant populations in the UK, who have higher prevalances of HBV infection. Data from the PROLIFICA programme on the natural history of HBV in the sub-Saharan African populations, where less is known, can be used to implement disease control & community outreach strategies in the UK.

3. Health Policy Makers, Governments & NGOs
In 2010, WHO adopted resolution WHA63.18, which called for a comprehensive approach to prevention and control of viral hepatitis, in which, my research can play one aspect in helping to achieve.

Modelling the impact of treatment strategies will hopefully help guide national and international governments, NGOs, funding agencies and other policy makers in implementation of treatment platforms and more research into this hugely neglected area.

I hope to use the outputs of my research to inform key NGOs, for example, MSF, who work on improving access to medication campaigns, by combining evidence from research and advocacy to decrease prices of medications for use in the developing world.

Strengthening health systems is one of DFIDs key aims in leading Britain's fight against global poverty. They rely on good quality research to inform their work. I hope that my research outputs will help inform their policy making and result in improvement of funding of similar sustainable HBV treatment initiatives, like PROLIFICA, in resource poor settings, to improve global health.

Governmental financial constraints in the developing world, limit the development of certain healthcare provisions. However, if an economic benefit is demonstrated to the country by limiting the morbidity of an economically active proportion of the society by offering treatment, more action is likely to be taken. Locally applicable analyses regarding CE and affordability, are important for clinicians and health policy makers to determine whether proposed Hepatitis B interventions constitute an effective use of resources.