Epidemiology of Hepatitis B in sub-saharan Africa 7 February 2018 Yusuke Shimakawa, MD, PhD Institut Pasteur
From the Big Three to the Big Four 1600000 Number of deaths/year 1400000 HAV + HEV 1200000 1000000 HCV 800000 600000 400000 200000 HBV 0 HIV TB Malaria Viral hepatitis Chen DS et al., Lancet Infect Dis, 2015
From the Big Three to the Big Four 1600000 Number of deaths/year 1400000 HAV + HEV 1200000 1000000 HCV 800000 600000 400000 200000 HBV 0 HIV TB Malaria Viral hepatitis Chen DS et al., Lancet Infect Dis, 2015
2016 2030 Finally targeted!!
Reducing: - the incidence of new chronic infection by 90% - the mortality from chronic infection by 65%
To increase the treatment coverage in chronic carriers eligible for antiviral therapy 2015 8% 2030 80% Reducing: - the incidence of new chronic infection by 90% - the mortality from chronic infection by 65%
Prevalence of HBsAg, 1990-2013 Schweitzer A et al., Lancet, 2015
Incidence of hepatocellular carcinoma, 2008 El-Serag HB et al., New Engl J Med, 2011
1. MOST PEOPLE HAVE BEEN EXPOSED TO HBV DURING CHILDHOOD
Modes of Transmission East Asia Sub-Saharan Africa Childhood (60%) MTCT (40%) Childhood (90%) MTCT (10%) Edmunds WJ et al., Epidemiol Infect, 1996
Sero-prevalence in children The Gambia
Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Whittle H et al., J Infect Dis, 1990
Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Horizontal transmission Whittle H et al., J Infect Dis, 1990
Sero-prevalence in children The Gambia Anti-HBc (+) only HBsAg(+) HBeAg(-) HBsAg(+) HBeAg(+) MTCT Horizontal transmission Whittle H et al., J Infect Dis, 1990
>75% have been exposed to HBV during childhood Kiire CF, Gut, 1996
2. TRANSMISSION DURING ADULTHOOD IS A MINOR ISSUE
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
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
Immunization coverage with 3rd dose of HepB vaccines in infants, 2014 0 1,050 2,100 4,200 Kilometers Source: WHO/UNICEF coverage estimates 2015 revision. July 2015. 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 2015. All rights reserved
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 2015. 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 2015. All rights reserved
3. LIVER CANCER IS A MAJOR PUBLIC HEALTH PROBLEM
Cancer deaths in Africa Jemal A et al., Cancer, 2012
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
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
Does HBV-related hepatocellular carcinoma occur at an early age in Africa??
N Mean age at HBV-related HCC Median age of population Europe 1039 58.0 41.7 USA 7060 56.0 38.0 East Asia 15871 54.5 37.9 Sub-Saharan Africa 126 38.9 18.3
N Mean age at HBV-related HCC Median age of population Europe 1039 58.0 41.7 USA 7060 56.0 38.0 East Asia 15871 54.5 37.9 Sub-Saharan Africa 126 38.9 18.3
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
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
Incidence rates (per 100 000 carrier-years) 1800 1600 1400 1200 1000 800 600 400 200 0 Age-specific incidence rates of HCC in male chronic HBV carriers in Gambia 25-34 35-44 45-54 55-64 65+ Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017
600 Age-specific incidence rates of HCC in men in The Gambia and in China Incidence rates (per 100 000) 500 400 300 200 100 0 0-14 15-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75+ The Gambia China Globocan 2012 (http://globocan.iarc.fr/default.aspx) Shimakawa Y & Lemoine M. Lancet Gastroenterol Hepatol, 2017
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