Epidemiology of Hepatitis B in sub-saharan Africa. 7 February 2018 Yusuke Shimakawa, MD, PhD Institut Pasteur

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1 Epidemiology of Hepatitis B in sub-saharan Africa 7 February 2018 Yusuke Shimakawa, MD, PhD Institut Pasteur

2 From the Big Three to the Big Four Number of deaths/year HAV + HEV HCV HBV 0 HIV TB Malaria Viral hepatitis Chen DS et al., Lancet Infect Dis, 2015

3 From the Big Three to the Big Four Number of deaths/year HAV + HEV HCV HBV 0 HIV TB Malaria Viral hepatitis Chen DS et al., Lancet Infect Dis, 2015

4 Finally targeted!!

5 Reducing: - the incidence of new chronic infection by 90% - the mortality from chronic infection by 65%

6 To increase the treatment coverage in chronic carriers eligible for antiviral therapy % % Reducing: - the incidence of new chronic infection by 90% - the mortality from chronic infection by 65%

7 Prevalence of HBsAg, Schweitzer A et al., Lancet, 2015

8 Incidence of hepatocellular carcinoma, 2008 El-Serag HB et al., New Engl J Med, 2011

9 1. MOST PEOPLE HAVE BEEN EXPOSED TO HBV DURING CHILDHOOD

10 Modes of Transmission East Asia Sub-Saharan Africa Childhood (60%) MTCT (40%) Childhood (90%) MTCT (10%) Edmunds WJ et al., Epidemiol Infect, 1996

11 Sero-prevalence in children The Gambia

12 Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Whittle H et al., J Infect Dis, 1990

13 Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Horizontal transmission Whittle H et al., J Infect Dis, 1990

14 Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Horizontal transmission Whittle H et al., J Infect Dis, 1990

15 >75% have been exposed to HBV during childhood Kiire CF, Gut, 1996

16 2. TRANSMISSION DURING ADULTHOOD IS A MINOR ISSUE

17 Acute hepatitis B Case series in Senegal, Chad, and Nigeria Only 0-22% carried anti-hbc IgM Difficult to recruit patients Pillot J et al., 1992, J Hepatol Crato M et al., 1993, Dakar Med Coursaget P et al., 1998, Am J Trop Med Hyg Buisson Y et al., 2000, J Gen Virol

18 Co-infection with HCV or HIV Major mode of transmission is different Prevalence of co-infection with HCV or HIV is not particularly high compared to those without chronic HBV infection In a population-based cohort of chronic HBV infection in The Gambia: HCV 0.3% (1/301) HIV 1.0% (3/301) Hoffmann CJ & Thio CL, Lancet Infect Dis, 2007 Shimakawa Y et al., Gut, 2016

19 Immunization coverage with 3rd dose of HepB vaccines in infants, ,050 2,100 4,200 Kilometers Source: WHO/UNICEF coverage estimates 2015 revision. July Map production: Immunization Vaccines and Biologicals, (IVB). World Health Organization Date of slide: 16 July 2015 <50% (7 countries or 4%) 50-79% (30 countries or 16%) 80-89% (32 countries or 17%) >=90% (115 countries or 62%) Not available / HepB not introduced or no coverage data available (10 countries or 5%) Not applicable The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved

20 Immunization coverage with 3rd dose of HepB vaccines in infants, 2014 Potential for epidemiological shift Past: >80% had naturally acquired & <20% of adults were susceptible 0 1,050 2,100 4,200 Kilometers Future?: High vaccine coverage: eliminate HBV Future?: Inadequate coverage: increasing age at HBV infection, Source: WHO/UNICEF coverage estimates 2015 revision. July Map production: Immunization Vaccines and Biologicals, (IVB). World Health Organization Date of slide: 16 July 2015 <50% (7 countries or 4%) resulting in more 50-79% acute (30 countries or hepatitis 16%) 80-89% (32 countries or 17%) >=90% (115 countries or 62%) Not available / HepB not introduced or no coverage data available (10 countries or 5%) Not applicable The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved

21 3. LIVER CANCER IS A MAJOR PUBLIC HEALTH PROBLEM

22 Cancer deaths in Africa Jemal A et al., Cancer, 2012

23 In The Gambia Hepatocellular carcinoma (HCC) is the most frequent type of cancer 60% are due to HBV infection Only <1% had heard about HBV infection and had been tested for HBV in the past Most people remains undiagnosed until later stages of disease when prognosis is poor and treatment options are limited Shimakawa Y et al., Int J Cancer 2013 Kirk GD et al., Hepatology 2004 Lemoine M, Shimakawa Y, et al., Lancet Glob Health 2016

24 No cure, no care! HCC patients referred to Liver Clinic (n=25) Median score Pain 4/5 (IQR: 3-5) Worry 5/5 (IQR: 2-5) None Shimakawa Y et al., Palliat Med 2015 Codeine

25 Does HBV-related hepatocellular carcinoma occur at an early age in Africa??

26 N Mean age at HBV-related HCC Median age of population Europe USA East Asia Sub-Saharan Africa

27 N Mean age at HBV-related HCC Median age of population Europe USA East Asia Sub-Saharan Africa

28 Need to take account of: 1- Difference in the age distribution of underlying population 2- Higher risk for competing causes of death in Africa The best way to address this question ÞAge-specific incidence rates of HCC in population-based cohort of chronic HBV carriers Þ Age-specific incidence rates of HCC in general population (with similar HBV prevalence) Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017

29 Need to take account of: 1- Difference in the age distribution of underlying population 2- Higher risk for competing causes of death in Africa The best way to address this question Þ Age-specific incidence rates of HCC in population-based cohort of chronic HBV carriers Þ Age-specific incidence rates of HCC in general population (with similar HBV prevalence) Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017

30 Incidence rates (per carrier-years) Age-specific incidence rates of HCC in male chronic HBV carriers in Gambia Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017

31 600 Age-specific incidence rates of HCC in men in The Gambia and in China Incidence rates (per ) The Gambia China Globocan 2012 ( Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017

32 Summary Most of people had been exposed to HBV during childhood Horizontal >> Mother-to-child Adulthood transmission is rare, but may change with inadequate infant vaccine coverage HCC: no cure, no care Early age at HCC development: questionnable