1. Hepatitis B elimination: from the bench to public health perspectives
Pr Karine Lacombe, M.D., PhD
Inserm UMR-S1136, IPLESP
Sorbonne Université, APHP
Paris - France

2. Chronic Hep B, a silent and neglected killer for years1
15M.
21M.
39M.
7M.
60M.
115M.
Incidence of HBV in children < 5 years
TOTAL: 257 M.
1Lemoine, J Hepatol Global Hepatitis Report 2017

3. High disease burden
HIV-HBV coinfection affects 2,7M individuals with higher risk of death after ARV initiation in those living in Africa1
≈ deaths due to sequelae of HepB (66% of all 1,34M. deaths from viral hepatitis): from HCC, from cirrhosis and from acute HepB2
Infection thats affect young individuals (30-40 years), women of child bearing age with high risk of transmission to babies
1Kouame, Clin Infect Dis Global Hepatitis Report 2017

4. SDG for 2030: viral hepatitis elimination
6-10 million infections  (in 2015)  to 900,000 infections (by 2030)
1.4 million deaths (in 2015) to under 500,000 deaths (by 2030)

5. Effective tools for HBV elimination
Without implementation of effective tools, between 2015 and 20301
63 millions new cases of HBV
17 millions HBV-related deaths
Prevention
Diagnosis
HBV Cure
HBV
Access to
Treatment
Nagayam, Lancet Glob Health 2016

6. From the bench: is HBV elimination feasible ?
1Thomas XV. PlosOne 2012.

7. High efficacy of current treatment…
Exemple of HIV-HBV coinfection: Meta-analysis on 23 papers including cohorts and clinical trials, n=516 on TDF
A small % continues to have detectable HBV-DNA after extended therapy
Price H et al., PLoS One 2013

8. … but no functional cure
Persistence of DNA synthesis despite « viral suppression »
New round of infection and/or replenishment of the cccDNA pool occur despite « viral suppression »
Boyd, J Hepatol 2016

9. Multiple targets in host and virus
Durantel D. J Hepatol 2016

10. Upcoming strategies for HBV cure ?
Antivirals
Host immunity stimulation
Prevent viral production and
Re-amplification of cccADN
Stimulating host immune response or prevent its inactivation
HBV functional cure
Inhibition of HBV antigen production
cccDNA inhibition
Inhibits the steps of replication cycle (entry, diffusion, capside formation, HBx functionning and HBsAg release)
Decrease or inhibition of cccDNA

11. From bench to public health: requirements to reach the WHO goals by 2030
How to avert new cases of Hep B ?
STATU QUO
HBV vaccine scale-up to 90%
HBV vaccine scale-up to 90%
AND HVB-PMTCT (80% mothers treated + birth dose vaccine)
HBV vaccine scale-up to 90%
AND HVB-PMTCT (80% mothers treated + birth dose vaccine) AND treatment of cases
Nagayam S. Lancet Glob Health 2016

12. Requirements to reach the WHO targets by 2030
How to decrease
HBV mortality ?
Statu quo
HBV vaccine scale-up to 90%
HBV vaccine scale-up to 90%
AND HVB-PMTCT (80% mothers treated + birth dose vaccine), treatment AND cure
HBV vaccine scale-up to 90%
AND HVB-PMTCT (80% mothers treated + birth dose vaccine), treatment of cases
HBV vaccine scale-up to 90% AND HVB-PMTCT (80% mothers treated + birth dose vaccine)
Nagayam S. Lancet Glob Health 2016

13. Impact of birth dose vaccine in Asia
HBsAg and Anti-HBs Ab dynamics in China after global implementation of immunization1
Impact of immunization in HCC occurrence in the long term (Taiwan)2
1Cui, Emerg Inf Dis 2017
2Chang, Gastroenterol 2016

14. HBV birth dose, a challenge in Africa
Hefferman, OFID 2018

15. HBV PMTCT, a never-ending story
Birth dose is not enough !
AgHBe pos.
AgHBe neg.
newborns infected each year in Africa
twice higher than HIV
Keane, APT 2017

16. Screening of HBV, a global challenge in LMIC
Failure of effective HBV-PMTC due to lack of screening
Technical limit:
No mean to accurately identify HBe Ag with POC
HBV-DNA measurement out of reach in most countries
Political will
Screening not provided for free
… this also leads to failure in identifying who is in need of treatment globally

17. Treatment eligibility and coverage, the challenging issue
9% of HBV-infected patients are aware of their status1
4 – 9% of screened patients in Africa are in need of treatment2
8% of those in need of treatment have access to treatment1
1Global Hepatitis Report Lemoine, Lancet Glob Health 2016

18. WHO Guidelines for global HBV screening and treatment
WHO HBV Guidelines 2015

19. New molecular tools for LMIC
Use of DBS for HBV-DNA1:
Se = 95%, Sp = 99%
Use of in-house quantitative PCR2:
Developped within the PROLIFICA project in Western Africa
Cost = 21€/test (3 to 5-fold less than commercial assays)
Use of in-house semi-qualitative PCR3
Threshold of detection set to 2000UI/mL
Detection of 95% of sample >2200UI/mL and 100% of samples < 1800UI/mL compared to commercial kits
POC HBV-DNA in the near future ?
1Lange, BMC Infect Dis Ghosh, J Viral Hepat Castéra-Guy, J Virol Meth 2017

20. A simple score to determine who is in need of treatment ?
Shimakawa, J Hepatol 2018

21. Performance of TREAT-B score
Shimakawa, J Hepatol 2018

22. Take home messages
Complex interaction between host and virus: not ALL patients have to be treated (at least in the absence of drugs that cure)
NO cure to date BUT vaccine (unlike HCV)
Elimination: immunization (birth dose) + screening (POC) + HBV-PMTCT (including treatment of mothers) + universal access to HBV drugs (± HBV cure)

23. Acknowledgements Maud Lemoine (Imperial College)
Yusuke Shimakawa (Pasteur Institute, Paris)
Anders Boyd (Inserm UMR-S1136, IPLESP)