Pause for thought on the missing millions affected by hepatitis B: Are we doing enough? World Hepatitis Day – 28th July 2019

 

 

 

By 2040, the number of deaths from viral hepatitis will be higher than the combined mortality arising from HIV, tuberculosis and malaria.1 There have been tremendous advances in fighting hepatitis C. Are we doing enough to lift the heavy burden of hepatitis B?

Worldwide, an estimated 257 million people have chronic hepatitis B virus (HBV) infection and one death every 30 seconds results from HBV-related complications – cirrhosis and liver cancer – totalling nearly a million deaths each year.1-4 The global incidence of hepatocellular carcinoma continues to climb, with HBV infection as a leading cause.5 In stark contrast, public health interventions over the past decades have sent incidence of many other cancers into decline. On a global scale, peak morbidity and mortality from HBV infection occurs in early and middle adulthood, preventing adults from fulfilling their roles in families, education, employment and economies. Disease often presents late, by which time interventions, when available, are costly and often futile – particularly in resource-limited settings.6 The need for enhanced, co-ordinated action is recognised by international sustainable development goals, endorsed by the WHO, which include an ambitious aim: to eliminate viral hepatitis as a public health threat by 2030.7

Safe and effective HBV vaccines have been available since the 1980’s, and there is no doubt that vaccination is a powerful tool to reduce the incidence of new infections, alongside strict enforcement of infection control measures related to medical interventions, including the safety of blood transfusions and the reuse of needles in healthcare settings.8 However, given the large reservoir of existing carriers, and the difficulty of establishing complete coverage of a 3-dose vaccine regimen, vaccination is not yet proving a complete solution.9 Indeed, despite wide-spread roll out of the vaccine since the early-1990’s as part of the WHO’s Expanded Programme on Immunisation, prevalence of chronic HBV infection remains above 6% in many parts of sub-Saharan Africa, South America, South-East Asia, and Antarctica. Across Europe and North America, high prevalence occurs in selected populations, such as those with links to endemic countries, but also people whose risk of infection include sexual exposure.10,11 Yet, the epidemiology of hepatitis B infection remains poorly characterised in many countries, a problem compounded by the lack of systematic testing of those at risk and incomplete surveillance programs.10 It is hardly surprising that globally fewer than 10% of chronic HBV carriers are aware of their status. Among those with a diagnosis, fewer than 10% are in appropriate care and receiving antiviral treatment.6

 

Treatment with highly effective antiviral drugs (tenofovir or entecavir) is successful in suppressing the virus, bringing benefits directly to the individual patient, as well as delivering a wider public health benefit by reducing the risk of transmission. However, antiviral therapy does not commonly result in clearance of infection, so long-term and possibly life-long treatment is usually necessary.12 In addition, treatment does not abolish the risk of liver cancer. Significant research efforts are ongoing to develop new HBV treatments of finite duration that may cure the infection. However, for existing and future treatment to be effective as a public health intervention, enhanced diagnosis is fundamental. Implementation of increasingly available, simple diagnostic and monitoring tools adapted to use outside of specialised laboratories can greatly benefit resource-limited as well as high-income settings, allowing expanded access to testing and simplified care pathways. Interventions can be tailored to the specific needs of different settings, in order to derive the maximum benefit for that population, balanced against the resources invested.13

 

Whilst a range of strategies can be proposed to improve diagnosis and linkage into care, a major challenge lies in the chronic, widespread neglect of viral hepatitis. The absence of activity, advocacy and intervention straddles domains of education, funding, political action, media coverage, translational and basic science research, public health and clinical care. Stigma is potentially powerful in preventing open recognition, discussion and advocacy, and is an active barrier to seeking diagnosis and treatment.14 There are few advocacy groups, few high-profile champions, few headlines about hepatitis B.

 

This conversation needs to progress. We need to make space to hear the voices of patients and their families, we need governments, pharma, academic and charity sectors to commit financial investment in multidisciplinary research, we need expansion of public health and clinically-driven interventions, we need to put hepatitis B firmly into the mainstream agenda.

Dear readers, please join our aspirations and help expand testing for hepatitis B and ‘Find the Missing Millions’, headlined for World Hepatitis Day.15

 

Philippa C Matthews1, Maud Lemoine2, Anna Maria Geretti3

  1. Nuffield Department of Medicine, University of Oxford, United Kingdom
  2. St Mary’s Hospital, Imperial College London, United Kingdome
  3. Institute of Infection and Global Health, University of Liverpool, United Kingdom

 

 

REFERENCES

  1. Thomas DL. Global elimination of chronic hepatitis. N Engl J Med 2019;380:2041-50.
  2. Global Health Estimates 2016. Available at: https://www.who.int/healthinfo/global_burden_disease/en/
  3. Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet 2016;388:1081-8.
  4. Hepatitis B Fact Sheet 2017. Available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
  5. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol 2017;3:1683-91.
  6. O’Hara GA, McNaughton AL, Maponga T, et al. Hepatitis B virus infection as a neglected tropical disease. PLoS Negl Trop Dis 2017;11:
  7. Griggs D, Stafford-Smith M, Gaffney O, et al. Policy: Sustainable development goals for people and planet. Nature 2013;495:305-307.
  8. Stockdale AJ, Geretti AM. Chronic hepatitis B infection in sub-Saharan Africa: a grave challenge and a great hope. Trans R Soc Trop Med Hyg 2015;109:421-2.
  9. Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis 2016;16:1399-1408.
  10. Evlampidou I, Hickman M, Irish C, et al. Low hepatitis B testing among migrants: a cross-sectional study in a UK city. Br J Gen Pract 2016;66:e382-91.
  11. van de Laar TJ, Van Gaever VA, Swieten PV, Muylaert A, Compernolle V, Zaaijer HL. Phylogenetic analysis reveals three distinct epidemiological profiles in Dutch and Flemish blood donors with hepatitis B virus infection. Virology 2018;515:243-9.
  12. Likhitsup A, Lok AS. Understanding the natural history of hepatitis B virus infection and the new definitions of cure and the endpoints of clinical trials. Clin Liver Dis 2019;23:401-16.
  13. Cooke GS, Andrieux-Meyer I, Applegate TL, et al. Accelerating the elimination of viral hepatitis. Lancet Gastroenterol Hepatol 2019;4:135-84.
  14. Mokaya J, McNaughton A, Burbridge L, et al. A blind spot? Confronting the stigma of hepatitis B virus (HBV) infection – A systematic review. Wellcome Open Res 2018;3:
  15. Available at: http://www.worldhepatitisalliance.org/find-missing-millions.

 

 

 

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