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. 2022 Sep;7(9):796-829.
doi: 10.1016/S2468-1253(22)00124-8. Epub 2022 Jun 21.

Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

GBD 2019 Hepatitis B Collaborators
Collaborators

Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

GBD 2019 Hepatitis B Collaborators. Lancet Gastroenterol Hepatol. 2022 Sep.

Abstract

Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets.

Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B.

Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [-5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [-5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000.

Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination.

Funding: Bill & Melinda Gates Foundation.

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Conflict of interest statement

Declaration of interests S Afzal reports participation on a data safety monitoring board or advisory board on the Corona Expert Advisory Group and Infectious Diseases Expert Advisory Group; leadership or fiduciary roles in other board, society, committee or advocacy groups, paid or unpaid, as a Fellow of the Faculty of Public Health (UK), and as the Dean of Public Health and Preventive Medicine, and the Chairperson of Medicine at the King Edward Medical University (Lahore, Pakistan); all outside the submitted work. R Ancuceanu reports consulting fees from AbbVie; payment or honoraria for lectures, presentations, speakers' bureau, manuscript writing, or educational events from from AbbVie, Sandoz, and B Braun; all outside the submitted work. M Ausloos reports grants from Romanian National Authority for Scientific Research and Innovation (CNDS-UEFISCDI; project number PN-III-P4-ID-PCCF-2016-0084 Oct 2018–Sep 2022), outside the submitted work. X Dai reports support for the present manuscript from the University of Washington (Seattle, WA, USA), through their employment at IHME. T M Drake reports grant funding from Aligod Therapeutics for research into primary liver cancer, outside the submitted work. C Herteliu reports grants from CNDS-UEFISCDI (project numbers PN-III-P4-ID-PCCF-2016-0084 Oct 2018–Sept 2022 and PN-III-P2–2.1-SOL-2020-2-0351 June 2020–Oct 2020), from the Romanian Ministry of Research Innovation and Digitalization (project number ID-585-CTR-42-PFE-2021 Jan 2022–June 2023), and from the Ministry of Labour and Social Justice, Romania (project number 30/PSCD/2018 Sept 2018–June 2019), outside the submitted work. L Hiebert reports grants or contracts through the Task Force for Global Health, which receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Cepheid, Roche, Pharco, Zydus-Cadila, and governmental agencies and philanthropic organisations; outside the submitted work. N E Ismail reports leadership or fiduciary roles in other board, society, committee or advocacy groups, unpaid, as a council member of the Malaysian Academy of Pharmacy, outside the submitted work. I M Karaye reports support for attending meetings or travel, or both, from Hofstra University for the Natural Hazards meeting and American College of Epidemiology Conference, outside the submitted work. J V Lazarus reports grants and consulting fees from AbbVie, Gilead Sciences, and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Gilead, Sciences, Intercept, Jannsen, and MSD; leadership or fiduciary roles in other board, society, committee or advocacy groups, unpaid, with the EASL international Liver Foundation; all outside the submitted work. J A Loureiro reports support for the present manuscript from Fundaçã o para a Ciência e Técnologia (FCT) under the Scientific Employment Stimulus (CEECINST/00049/2018). P C Matthews reports support for the present manuscript from the Welcome Trust through the Intermediate Clinical Fellowship (grant Ref 110110/Z/15/Z); grants or contracts from GlaxoSmithKline as a contribution to their PhD stipend; and royalties from Oxford University Press for the publication of a medical textbook; all outside the submitted work. O O Odukoya reports support for the present manuscript from the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. M J Postma reports stock or stock options in HealthEcore and PAG, outside the submitted work. A Pana reports grants from CNDS-UEFISCDI (project numbers PN-III-P4-ID-PCCF-2016–0084 Oct 2018–Sep 2022 and PN-III-P2–2·1-SOL-2020–2-0351 June 2020–Oct 2020), outside the submitted work. J Sanabria reports grants for contracts from Marshall University School of Medicine and Joan Edwards Comprehensive Cancer Center (Huntington, WV, USA); patents planned, issued, or pending for pNaKtide for the treatment of hepatocellular carcinoma related to NASH and NASH; participation on a data safety monitoring board or advisory board with the Department of Surgery, Marshall University, as a quality assessment and assurance officer; leadership or fiduciary roles in other board, society, committee or advocacy groups, and unpaid roles with several national and international surgical societies; all outside the submitted work. J A Singh reports consulting fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs, Adept Field Solutions, Clinical Care options, Clearview Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, MedIQ, Jupiter Life, UBM, Trio Health, Medscape, WebMD, Practice Point Communications, the US National Institutes of Health, and the American College of Rheumatology; payment or honoraria for participating in the speakers bureau for Simply Speaking; support for attending meetings or travel, or both, from the steering committee of OMERACT, to attend their meeting every 2 years; participation on a data safety monitoring board or advisory board as an unpaid member of the US Food and Drug Administration (FDA) Arthritis Advisory Committee; leadership or fiduciary roles in other board, society, committee or advocacy groups, paid or unpaid, as a member of the steering committee of OMERACT, an international organisation that develops measures for clinical trials and receives arms' length funding from 12 pharmaceutical companies, with the Veterans Affairs Rheumatology Field Advisory Committee as Chair, and with the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis as a director and editor; stock or stock options in TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Series Therapeutics, Tonix Pharmaceuticals, and Charlotte's Web Holdings; and previously owned stock options in Amarin, Viking, and Moderna; all outside the submitted work. J W Ward reports grants or contracts through The Task Force for Global Health, which receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Cepheid, Roche, Pharco, Zydus-Cadila, governmental agencies and philanthropic organisations; membership on an advisory board, unpaid, with the international Coalition to Eliminate HBV, and membership on an advisory committee, unpaid, for the Longevity Project for HCV at the University of Liverpool (UK); all outside the submitted work.

Figures

Figure 1
Figure 1
Geographical distribution of the prevalence and death rate of hepatitis B in 2019 (A) All-age HBsAg prevalence in 2019. (B) HBsAg prevalence in children younger than 5 years in 2019. (C) All-age death rate per 100 000 for HBV-related diseases in 2019. HBV=hepatitis B virus.
Figure 2
Figure 2
Global age-specific HBsAg prevalence (A), HBV-related death rate per 100 000 (B), and HBV-related DALY rate per 100 000 (C), in 1990, 2015, and 2019 HBV=hepatitis B virus. DALY=disability-adjusted life-year.
Figure 3
Figure 3
HBV-related death rates for all ages (A), HBsAg prevalence for all ages (B), and HBsAg prevalence in children younger than 5 years (C) by SDI quintile, 1990–2019 The vertical dashed line indicates the WHO-GHSS baseline year of 2015. The shading represents 95% uncertainty intervals. HBV=hepatitis B virus. SDI=Socio-demographic Index. WHO-GHSS=WHO Global Health Sector Strategy on Viral Hepatitis.
Figure 4
Figure 4
Changes in mortality by WHO region over time Percentage change in HBV-related death counts, all ages from 1990 to 2019 (A) and from 2015 to 2019 (B). The dashed line indicates the WHO-GHSS 2020 target of a 10% reduction in death counts. Error bars depict 95% uncertainty intervals. WHO-GHSS=WHO Global Health Sector Strategy on Viral Hepatitis.
Figure 5
Figure 5
Proportion of countries by WHO region that met or exceeded WHO-GHSS and WHO Interim Guidance provisional targets (A) WHO-GHSS 2020 target of 10% reduction in deaths due to viral hepatitis from 2015 to 2020. (B) WHO-GHSS 2020 target of 30% reduction in new cases of viral hepatitis from 2015 to 2020. (C) Proxy target of less than 1% prevalence of viral hepatitis in infants and children younger than 5 years by 2020. (D) WHO Interim Guidance provisional mortality target of less than or equal to four deaths per 100 000. (E) WHO-GHSS proxy target of less than or equal to 0·1% prevalence in infants and children younger than 5 years by 2030. The numbers inside the bars represent the number of countries by WHO region that met or did not meet the specific targets. WHO-GHSS=WHO Global Health Sector Strategy on Viral Hepatitis.
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