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      A new approach to prevent, diagnose, and treat hepatitis B in Africa

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          Abstract

          There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.

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          Most cited references73

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          Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance.

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            Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update

            Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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              Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.

              Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system). Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug. In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. Gilead Sciences. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                wendy.spearman@uct.ac.za
                Journal
                BMC Glob Public Health
                BMC Glob Public Health
                BMC Global and Public Health
                BioMed Central (London )
                2731-913X
                2 November 2023
                2 November 2023
                2023
                : 1
                : 1
                : 24
                Affiliations
                [1 ]Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, ( https://ror.org/03p74gp79) Cape Town, South Africa
                [2 ]GRID grid.410556.3, ISNI 0000 0001 0440 1440, Oxford University Hospitals NHS Foundation Trust, ; Oxford, UK
                [3 ]Radcliffe Department of Medicine, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK
                [4 ]Division of Medical Virology, University of Stellenbosch, ( https://ror.org/05bk57929) Stellenbosch, South Africa
                [5 ]LiveWell Initiative, Yesuf Abiodun Street, Victoria Island, Lagos, Nigeria
                [6 ]Women in Hepatitis Africa, Womens Wellness Center for Hepatitis, Isale Ajoke, Iwaya-Makoko, Lagos State, Nigeria
                [7 ]Department of Internal Medicine, Jos Univeristy Teaching Hospital, ( https://ror.org/042vvex07) Jos, Nigeria
                [8 ]Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, ( https://ror.org/04ax47y98) Addis Ababa, Ethiopia
                [9 ]Hepato-Gastroenterology Department, Bogodogo University Hospital Center, Ouagadougou, Burkina Faso
                [10 ]Department of Infectious Diseases, Vestfold Hospital Trust, ( https://ror.org/04a0aep16) Tønsberg, Norway
                [11 ]Institute of Clinical Medicine, University of Oslo, ( https://ror.org/01xtthb56) Oslo, Norway
                [12 ]The National Organisation for People Living With Hepatitis B, Kampala, Uganda
                [13 ]Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, ( https://ror.org/041kmwe10) London, UK
                [14 ]Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, The Gambia
                [15 ]The Francis Crick Institute, ( https://ror.org/04tnbqb63) 1 Midland Road, London, NW1 1AT UK
                [16 ]Division of Infection and Immunity, University College London, ( https://ror.org/02jx3x895) Gower Street, London, WC1E 6BT UK
                [17 ]Department of Infectious Diseases, University College London Hospital, ( https://ror.org/02jx3x895) Euston Road, London, NW1 2BU UK
                [18 ]Department of Clinical Sciences and International Public Health, Liverpool School of Tropical Medicine, ( https://ror.org/03svjbs84) Liverpool, UK
                [19 ]Institut Pasteur, Université Paris Cité, Unité d’Épidémiologie Des Maladies Émergentes, Paris, France
                [20 ]Service d’hépato-Gastroentérologie, CHU Yalgado OUÉDRAOGO, Université Joseph KI-ZERBO, ( https://ror.org/00t5e2y66) Ouagadougou, Burkina Faso
                [21 ]Malawi Liverpool Wellcome Trust Clinical Research Programme, ( https://ror.org/03tebt685) Blantyre, Malawi
                [22 ]Department of Clinical Infection, Microbiology and Immunity, University of Liverpool, ( https://ror.org/04xs57h96) Liverpool, UK
                [23 ]GRID grid.417371.7, ISNI 0000 0004 0635 423X, Division of Infectious Diseases, Department of Medicine, , Tygerberg Hospital and Stellenbosch University, ; Cape Town, South Africa
                [24 ]GRID grid.265892.2, ISNI 0000000106344187, School of Medicine, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [25 ]Centre for Infectious Disease Research in Zambia, ( https://ror.org/02vsy6m37) Lusaka, Zambia
                [26 ]School of Medicine, University of Zambia, ( https://ror.org/03gh19d69) Lusaka, Zambia
                [27 ]Department of Infectious Diseases, Bern University Hospital, University of Bern, ( https://ror.org/02k7v4d05) Bern, Switzerland
                [28 ]Department of Medicine, Jos University Teaching Hospital, ( https://ror.org/042vvex07) Jos, Nigeria
                Article
                26
                10.1186/s44263-023-00026-1
                11116268
                ea18df96-276f-4c5d-bd38-bedf3ce203c9
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 July 2023
                : 2 October 2023
                Funding
                Funded by: GILEAD Sciences for the Women Hepatitis Champions Training in Mauritius, Nigeria and Egypt
                Funded by: Received funding from GILEAD Sciences for NOPLHB
                Funded by: Received funding from MRC UKRI.
                Funded by: Wellcome Trust
                Award ID: 110110/Z/15/Z
                Award Recipient :
                Funded by: The Francis Crick Institute
                Funded by: UCL NIHR Biomedical Research Centre
                Funded by: Received funding from GILEAD Sciences for research
                Funded by: Research funding from GILEAD Sciences and research materials from Abbott and Fujirebio Inc.
                Funded by: National Institute for Health and Care Research (UK) Senior Clinical Lectureship at the University of Liverpool
                Funded by: U.S. National Institutes of Health Grant
                Award ID: R01AI147727
                Award Recipient :
                Funded by: Supported by a Professorship grant from the Swiss National Science Foundation
                Award ID: PP00P3_211025
                Award Recipient :
                Funded by: Received unrestricted research grants from Gilead Sciences and Roche Diagnostics
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                © BioMed Central Ltd. part of Springer Nature 2023

                hepatitis b,africa,advocacy,prevention,treatment
                hepatitis b, africa, advocacy, prevention, treatment

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