Management of chronic hepatitis B in Africa: is a one-stop assessment of liver disease enough? The MATCH-B study
Lead Research Organisation:
Imperial College London
Department Name: Surgery and Cancer
Abstract
Infection with hepatitis B virus (HBV) is a major public health issue worldwide with about 250 million people chronically infected. HBV is an important cause of severe liver disease including liver cancer, which has a poor prognostic. Although an effective vaccine is available to prevent HBV transmission, many people are not vaccinated in particular in Africa and get infected with a risk of serious hepatic complications. The World Health Organization (WHO) has recently recognized HBV infection as an important health threat and has called for scaling up screening and treatment interventions for hepatitis B globally in order to control HBV-related mortality by 2030 and eventually eliminate the infection. Significant progress has been made in the management of HBV-infected patients. A highly effective treatment is now available at low cost in many countries and is recommended to the most severe patients with active hepatitis. However in developing countries, which account for 80% of the HBV epidemic, interventions to fight against hepatitis B are very limited. In Africa about 80 million people are estimated to be chronically infected with HBV. Yet screening and treatment interventions and research activities to fight against hepatitis B are almost inexistent in Africa. The complexity and high cost of the current international recommendations for the management of hepatitis B represent one of the barriers to scale up HBV screening and treatment interventions in Africa. The first screen-and-treat programme for hepatitis B in Africa called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) has been set up in 2011 in Gambia and Senegal. With the support of the Gambian and Senegalese Ministries of Health and the local communities, the programme has been very successful: almost 20,000 persons have been screened for HBV and about 2,000 infected persons have been offered clinical assessment, and 283 given antiviral treatment. PROLIFICA has also generated unique data on chronic hepatitis B in Africa, which have informed the WHO and the local Ministries of Health on the burden of hepatitis B in West Africa. The study demonstrated that the vast majority of HBV-infected adults in West Africa have inactive or mild hepatitis and do not require immediate treatment. However, whether these patients remain so without liver disease progression in mid- to long-term or do they require regular follow-up as they may develop liver complications is unknown in Africa. In addition whether HBV antiviral therapy is effective and safe to control liver complications has never been demonstrated. Within the following study, we propose to re-assess the liver disease of the 2,108 patients (untreated or treated) previously enrolled in the PROLIFICA programme. We will re-invite each patient previously enrolled in the programme in Gambia and Senegal for a comprehensive liver assessment. Infected subjects with liver disease progression will be given treatment. This study will therefore address two key unknown questions for Africa: 1/ What is the rate of liver disease progression in African patients with inactive or mild hepatitis B exposed to the African environment and can they be offered a limited monitoring? 2/ Is HBV antiviral therapy effective and safe to reduce hepatic liver complications in patients with active chronic hepatitis B in Africa? If we demonstrate that patients diagnosed to have inactive or mild hepatitis B at one single time point have no significant liver disease progression over time, it may be unnecessary to do the conventional frequent follow-up for the millions of patients with mild hepatitis B in Africa. This will save considerable amount of resources since healthcare resources are seriously limited in Africa. We believe that our study will also promote awareness on hepatitis B and its findings will eventually contribute to the development of simplified guidelines for the management of HBV infection in Africa.
Technical Summary
Infection with hepatitis B virus (HBV) is highly endemic in Africa and is a leading cause of death mainly from cirrhosis and hepatocellular carcinoma. The World Health Organization has recently called for HBV elimination and scaling up screen-and-treat interventions in particular in sub-Saharan Africa.
Between 2011-2014 the PROLIFICA project-the first "screen-and-treat" intervention for HBV in Africa-has demonstrated that the vast majority (90%) of HBV-infected adults in west Africa are inactive carriers (IC) and do not require antiviral therapy. Whether these subjects are at risk of liver disease progression and need regular follow-up is unknown in the African settings. The aim of this study is 1) to determine the rate of HBV reactivation and liver disease progression in HBV inactive carriers in Africa and 2) the efficacy of antiviral therapy to reduce HBV-related complications in the African context.
We will re-assess the untreated (n=1,825) and treated patients (n=283) previously enrolled in the PROLIFICA project. Using reference tests (e.g HBV DNA and Fibroscan) patients will be re-assessed after a minimum of 4 years following the first liver assessment. In the untreated cohort (mainly IC) the primary objective will be to determine whether patients who did not meet treatment eligibility criteria at baseline remain so without progression of liver disease. In the treatment cohort the primary objective will be to assess the clinical effectiveness of tenofovir in West African patients. If untreated patients do not exhibit significant liver progression it may be possible to limit the number of follow-up of the millions of patients with inactive hepatitis B in Africa where healthcare resources are seriously limited.
This study will provide unique longitudinal data on chronic hepatitis B in Africa and will therefore contribute to the development of national and regional strategies for the control of HBV infection in Africa adapted to the local environment.
Between 2011-2014 the PROLIFICA project-the first "screen-and-treat" intervention for HBV in Africa-has demonstrated that the vast majority (90%) of HBV-infected adults in west Africa are inactive carriers (IC) and do not require antiviral therapy. Whether these subjects are at risk of liver disease progression and need regular follow-up is unknown in the African settings. The aim of this study is 1) to determine the rate of HBV reactivation and liver disease progression in HBV inactive carriers in Africa and 2) the efficacy of antiviral therapy to reduce HBV-related complications in the African context.
We will re-assess the untreated (n=1,825) and treated patients (n=283) previously enrolled in the PROLIFICA project. Using reference tests (e.g HBV DNA and Fibroscan) patients will be re-assessed after a minimum of 4 years following the first liver assessment. In the untreated cohort (mainly IC) the primary objective will be to determine whether patients who did not meet treatment eligibility criteria at baseline remain so without progression of liver disease. In the treatment cohort the primary objective will be to assess the clinical effectiveness of tenofovir in West African patients. If untreated patients do not exhibit significant liver progression it may be possible to limit the number of follow-up of the millions of patients with inactive hepatitis B in Africa where healthcare resources are seriously limited.
This study will provide unique longitudinal data on chronic hepatitis B in Africa and will therefore contribute to the development of national and regional strategies for the control of HBV infection in Africa adapted to the local environment.
Planned Impact
In 2011 was set up the first screen-and-treat programme for hepatits B in Africa (in Gambia and Senegal), called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa). With the support of the Gambian and Senegalese ministry of health and the local communities, the programme has been very successful. By screening more than 16,000 subjects and assessing the liver disease of about 2,000 HBV-infected patients PROLIFICA has generated unique data on chronic hepatitis B in Africa, which have informed the World Health organization (WHO) and the local ministry of health on the burden of hepatitis B in West Africa.
HBV treatment has been given to the most severe patients (n=257) according to the international guidelines.
The programme activities have now ended. However, care and treatment are still provided to the treated patients thanks to the support of the local partners. However the untreated HBV-infected subjects (mainly inactive carriers) who did not require treatment at diagnosis do not benefit from regular clinical and virological follow-up. As a result whether these untreated patients have progressed to significant liver disease and now require treatment is unknown.
Within the following study, we propose to reinvite each patient previously enrolled in the PROLIFICA programme in Gambia and Senegal for a comprehensive liver assessment in order to determine 1) the rate of liver disease progression in untreated HBV-infected patients in Africa and 2) the efficacy and safety of antiviral therapy in treated patients.
The following study will direclty impact:
1) the patients who will receive care, treatment and support.
2) the local healthcare workers and team members who will benefit from education and training on the management of liver disease.
3) the Senegalese and Gambian ministry of health and national programme on viral hepatitis who will get stronger data and simplified algorithms for the management of hepatitis B;these data will be used to develop strategic plans against hepatitis B adapted to the local setting.
5) the WHO viral hepatitis unit that will use our results to update the guidelines on the management of hepatitis B in Africa
6) the African and international community of researchers and clinicians working on HBV infection (e.g see letter of support from ICE-HBV).
7) The study will also indirectly impact the patient associations in Gambia, Senegal and more broadly in Africa and non-governmental organizations fighting against HBV in Africa since our study will raise awareness and promote advocacy.
Our study will therefore have a triple impact: 1) societal & political, 2) academic and 3) economic.
Partners and Impacts are summarized in the figure attached to the "Pathway to impact" document in annex. Please see this document in annex.
HBV treatment has been given to the most severe patients (n=257) according to the international guidelines.
The programme activities have now ended. However, care and treatment are still provided to the treated patients thanks to the support of the local partners. However the untreated HBV-infected subjects (mainly inactive carriers) who did not require treatment at diagnosis do not benefit from regular clinical and virological follow-up. As a result whether these untreated patients have progressed to significant liver disease and now require treatment is unknown.
Within the following study, we propose to reinvite each patient previously enrolled in the PROLIFICA programme in Gambia and Senegal for a comprehensive liver assessment in order to determine 1) the rate of liver disease progression in untreated HBV-infected patients in Africa and 2) the efficacy and safety of antiviral therapy in treated patients.
The following study will direclty impact:
1) the patients who will receive care, treatment and support.
2) the local healthcare workers and team members who will benefit from education and training on the management of liver disease.
3) the Senegalese and Gambian ministry of health and national programme on viral hepatitis who will get stronger data and simplified algorithms for the management of hepatitis B;these data will be used to develop strategic plans against hepatitis B adapted to the local setting.
5) the WHO viral hepatitis unit that will use our results to update the guidelines on the management of hepatitis B in Africa
6) the African and international community of researchers and clinicians working on HBV infection (e.g see letter of support from ICE-HBV).
7) The study will also indirectly impact the patient associations in Gambia, Senegal and more broadly in Africa and non-governmental organizations fighting against HBV in Africa since our study will raise awareness and promote advocacy.
Our study will therefore have a triple impact: 1) societal & political, 2) academic and 3) economic.
Partners and Impacts are summarized in the figure attached to the "Pathway to impact" document in annex. Please see this document in annex.
Publications
Bassoum O
(2020)
Coverage and Timeliness of Birth Dose Vaccination in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.
in Vaccines
Cohen D
(2019)
[Prevention of liver fibrosis and liver cancer linked to hepatitis B virus in Africa: the Prolifica study].
in Medecine sciences : M/S
Cohen D
(2020)
Hepatitis B virus preS2?38-55 variants: A newly identified risk factor for hepatocellular carcinoma.
in JHEP reports : innovation in hepatology
Cooke G
(2019)
Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission
in The Lancet Gastroenterology & Hepatology
Cox AL
(2020)
Progress towards elimination goals for viral hepatitis.
in Nature reviews. Gastroenterology & hepatology
Ford N
(2018)
Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis.
in Hepatology communications
Johannessen A
(2023)
Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa.
in Nature communications
Lemoine M
(2021)
Improving disease knowledge is critical to eliminate hepatitis B
in Journal of Viral Hepatitis
Lô G
(2019)
Hepatitis B virus (HBV) infection amongst children in Senegal: current prevalence and seroprotection level.
in The Pan African medical journal
McNaughton AL
(2021)
Extending treatment eligibility for chronic hepatitis B virus infection.
in Nature reviews. Gastroenterology & hepatology
Nayagam S
(2020)
Mother-to-child transmission of hepatitis B: What more needs to be done to eliminate it around the world?
in Journal of viral hepatitis
Ndow G
(2023)
Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study.
in The Lancet. Global health
Post G
(2021)
Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B.
in Journal of viral hepatitis
Shimakawa Y
(2019)
Performance of two simplified HBV treatment criteria (TREAT-B score and WHO guidelines) in Burkina Faso, West Africa.
in Journal of hepatology
Shimakawa Y
(2020)
Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Shimakawa Y
(2018)
Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa.
in Journal of hepatology
Sonderup MW
(2020)
Hepatitis B in sub-Saharan Africa-How many patients need therapy?
in Journal of viral hepatitis
Description | ANRS Scientific Advisory Board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Gilead Advisory Board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Collaboration with Gilead as a member of their advisory board. The focus of the advisory board is how to achieve the HBV elimination targets in Africa, established by WHO. |
Description | The Gambian National Hepatitis Programme, Viral Hepatitis Unit WHO |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | The research has informed WHO policy in viral hepatitis as well as the Gambian National Hepatitis Programme. |
Description | Training of Clinical PhD Student |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Gibril's PhD research is nested within the PROLIFICA project and investigated: 1/ the prevalence and role of occult hepatitis B in liver disease progression in The Gambia; 2/ the rate and risk factors of liver disease progression among adults with chronic hepatitis B infection who did not meet the EASL criteria for antiviral therapy 3/ the safety and efficacy of antiviral therapy in Africans receiving Tenofovir 4/ the uptake of hepatitis B testing and treatment in HIV facilities in The Gambia He has reassessed approx. 800 patients with chronic HBV infection previously enrolled in the PROLIFICA study in The Gambia, and screened an addition 860 HIV patients in the largest HIV treatment centre in The Gambia. Gibril's PhD research at the HIV centre brought liver and viral hepatitis care and services to patients who otherwise do not have access to it. The follow-up reassessment of the PROLIFICA cohort, as part of the MATCH-B study, ensures continuity of care for the 1,180 patients with chronic hepatitis B in this cohort. |
Description | Cepheid funding: validation of the clinical and virological performance of the new GeneXpert HBV DNA kits |
Amount | £5,000 (GBP) |
Organisation | Cepheid |
Sector | Private |
Country | United States |
Start |
Description | Gilead - fellowship |
Amount | $100,000 (USD) |
Organisation | Gilead Sciences, Inc. |
Sector | Private |
Country | United States |
Start | 03/2019 |
End | 05/2021 |
Description | Gilead Sciences research funding |
Amount | $140,000 (USD) |
Organisation | Gilead Sciences, Inc. |
Sector | Private |
Country | United States |
Start | 07/2018 |
End | 07/2019 |
Description | ISSF Global Health Clinical Research Training Fellowship |
Amount | £35,400 (GBP) |
Organisation | Imperial College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2022 |
End | 12/2022 |
Description | Management of chronic hepatitis B in Africa: is a one-stop assessment of liver disease enough? The MATCH-B study |
Amount | £882,167 (GBP) |
Funding ID | MR/R011117/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2018 |
End | 07/2021 |
Description | Gilead - supply of drug |
Organisation | Gilead Sciences, Inc. |
Country | United States |
Sector | Private |
PI Contribution | Clinical and scientific expertise |
Collaborator Contribution | Supply of drug used in the study |
Impact | Research still ongoing. Publications expected soon. |
Start Year | 2011 |
Description | IRESSEF Senegal |
Organisation | Institute for Health Research, Epidemiological Surveillance and Training |
Country | Senegal |
Sector | Charity/Non Profit |
PI Contribution | Financial support. Academic support Clinical and scientific expertise |
Collaborator Contribution | Recruitment of patients Clinical and lab assessment Training Link with ministry of health Provide staff and admin support Data management |
Impact | Publications in high impact journals Presentations in international conferences Collaboration with WHO and other health policy makers Clinical and academic training |
Start Year | 2011 |
Description | MRC Gambia |
Organisation | Medical Research Council (MRC) |
Department | MRC Unit, The Gambia |
Country | Gambia |
Sector | Public |
PI Contribution | Financial support Academic support Clinical and scientific expertise |
Collaborator Contribution | Recruitment of patients Clinical and lab assessment Training Link with ministry of health Provide staff and admin support Data management |
Impact | Publications in high impact journals (>25 publications) Presentations in international conferences Collaboration with WHO and other health policy makers Clinical and academic training (3 completed PhD, 2 ongoing PhD, 1 Postdoc, 2 Mph) |
Start Year | 2011 |
Title | Tenofovir |
Description | Provision of Tenofovir under international guidelines |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Market authorisation |
Development Status | Under active development/distribution |
Impact | No other impacts |
Description | American Association for the Study of Liver Diseases (AASLD) panel discussion on viral hepatitis |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Panel discussion of the health consequences of Hepatitis B and Hepatitis C at the AASLD 2021 with Mark Sulkowski, Margaret Hellard and Norah Terrault which sparked further discussion and feedback from the audience. |
Year(s) Of Engagement Activity | 2021 |
Description | Contribution to a MOOC (massive open on line courses) on viral hepatitis organised by Pasteur Institue International |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | This MOOC is an education programme on viral hepatitis run by the Pasteur Institute in France. Professor Lemoine contributed to the programme. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.fun-mooc.fr/courses/course-v1:pasteur+96017+session01/about |
Description | Interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Education about hepatitis in Africa B and associated with a publication press release, organised by Imperial |
Year(s) Of Engagement Activity | 2018 |
Description | MRC Gambia Researcher Presentations at 4th COLDA Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Researchers from the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program at the Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine (MRCG at LSHTM) recently led presentations at the 4th annual Conference on Liver Disease in Africa (COLDA). Three of the team members received Young Investigator awards for the conference. The virtual conference, held from 9th to 11th September 2021, created a platform for researchers, healthcare workers and policy makers to share knowledge and best practices on the management of viral hepatitis and liver disease in Africa. Professor Maud Lemoine delivered an oral lecture on the experiences in The Gambia. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.mrc.gm/mrcg-at-lshtm-researchers-shine-at-4th-colda-conference/ |
Description | Patient Association in Gambia |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Education and support to patients for the screening, treatment and follow-up for hepatitis B. |
Year(s) Of Engagement Activity | 2018 |
Description | Project website www.prolifica.africa |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | The project website, which has been live since 2018, aims to engage the public by providing information on hepatitis research. The website acts as a repository for resources and provides links to updates, articles and further information such as key collaborators and funding bodies. The website also aims to educate the audience on hepatitis research, providing clear, accessible information to patients, the public and researchers. We also have developed a twitter account @ProlificaA |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.prolifica.africa/ |