The elimination of hepatitis B will not be achieved through innovation alone. It requires dismantling the structural inequities that have long constrained who leads, funds and benefits from global hepatitis B research.

This multicentre study investigated the utility of next-generation sequencing (NGS) to detect and generate hepatitis B virus (HBV) genomes in samples of low viral load (from 0.2 to 6207 IU/mL). 23 HBV DNA-positive plasma samples of genotypes A-E and one HBV-negative control sample were assayed blindly via 9 established NGS methods from 6 European laboratories. Methods included untargeted metagenomics, pre-enrichment by probe-capture followed by Illumina sequencing, and HBV-specific PCR pre-amplification followed by sequencing with Nanopore or Illumina. Full HBV genomes were obtained only from samples with viral loads > 1000 IU/mL using probe-capture methods, > 200 IU/mL using PCR-Illumina methods, > 10 IU/mL using PCR-Nanopore methods, and in no samples using metagenomic methods. Contamination was observed in the negative control and samples with very low viral loads in PCR-based methods. Probe-capture and metagenomic methods detected additional viruses not routinely screened in blood donations, including polyomaviruses and herpesviruses; positive results were confirmed by PCR. In conclusion, NGS may delineate whole-genome sequences at low viral loads if supported by a PCR pre-amplification step. Probe-capture methods also reliably detect HBV without pre-amplification but show limited genome coverage for samples with low viral loads; they may additionally detect a wide range of blood-borne viruses.

Abstract Introduction International goals aim to eliminate Hepatitis B Virus (HBV) as a public health threat by 2030, but data representing African populations remain limited. We therefore investigated the population prevalence of HBV and treatment eligibility in a rural South African setting. Methods We tested archived plasma samples from 2200 participants in a population-based study in KwaZuku Natal for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), and HBV surface antibody (anti-HBs). For samples testing HBsAg-positive, we quantified alanine transferase (ALT) and HBV DNA viral load. We evaluated demographic and clinical correlates of HBV biomarkers, explored the geographical distribution of HBsAg, and assessed HBV treatment eligibility. Results Weighted HBV infection prevalence was 10.4% (95% CI: 9.0%-12.1%). Evidence of HBV exposure and clearance was found in 34.9% (95% CI: 32.4 - 37.5). Overall prevalence of vaccine-mediated HBV immunity was 8.9% (95% CI: 7.5%-10.4%) but for the sub-group born between 2000-2005 (after the HBV vaccine was implemented) this increased to 20.2% (95% CI 15.8-25.4). Infection prevalence was highest in the South of the region. Over 60% of individuals testing HBsAg-positive met treatment eligibility criteria. Conclusion Prevalence of HBV infection and exposure in this setting is high, while vaccine-mediated immunity is low. These data highlight a pressing need for scale-up of interventions to support progress towards global elimination targets. Funding The Francis Crick Institute (ref. CC2223), the Africa Oxford Initiative (Research Development Award) and Wellcome Strategic Core Award (227167/A/23/z). Ethics University of KZN (UKZN) ref. 00004495/2022; University College London ref. 23221/001.

Introduction An estimated 254 million people are living with chronic hepatitis B virus (CHB) and 1.6 billion with metabolic dysfunction-associated steatotic liver disease (MASLD) worldwide. CHB remains a major global health challenge, despite a robust vaccine and suppressive antiviral treatment, and MASLD prevalence is increasing in line with a rise in cardiometabolic risk factors, such as obesity and type 2 diabetes. Thus, understanding the impact of concurrent CHB and MASLD on liver health is important to inform clinical practice and population surveillance. Current literature, including over ten systematic reviews and meta-analyses, yields conflicting evidence about the interplay between CHB and MASLD. This protocol describes a study aiming to critically appraise published systematic reviews investigating the effect of MASLD on liver outcomes in people living with CHB, identify gaps in the available data and assist scientists and clinicians in informing future research design. Methods and analysis We will use umbrella review methodology from the Joanna Briggs Institute (JBI) to evaluate and synthesise evidence from existing systematic reviews and meta-analysis investigating liver and viral outcomes (fibrosis, cirrhosis, hepatocellular carcinoma, response to antiviral treatment, and impact on CHB biomarkers e.g. hepatitis B surface antigen, hepatitis B e-antigen and viral load) in CHB and MASLD, compared to CHB alone. We will search Ovid Medline, Ovid Embase, PubMed and Web of Science. We will assess methodological quality using the Assessing the Quality of Systematic Reviews-2 (AMSTAR-2) tool, compare study characteristics and present important results. Ethics and dissemination No ethics approval is required as we will use only data from systematic reviews that are already published. Results will be included in a PhD thesis, submitted for consideration for presentation at international conferences and for peer review for publication in a scientific journal. We will endeavour to share results with relevant public and patient organisations. Registration details This umbrella review has been published on PROSPERO (ID CRD420261308282).

Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain public health threats in the WHO European region, where an estimated 29 million people live with chronic infection and viral hepatitis-related deaths now surpass those from HIV/AIDS and tuberculosis combined. Although effective prevention tools and antiviral treatments reduce the risk of complications, overall mortality has not declined. This Series paper reviews models of care (MoC) implemented between 2015 and 2025, drawing on scientific literature and policy documents to assess regional progress. Simplified testing and treatment, childhood and targeted adult HBV vaccination, harm-reduction programmes, and prison-based interventions have advanced elimination efforts. Pragmatic approaches, including point-of-care testing, decentralised services, and integrated models tailored to key populations demonstrate clear benefits. However, major challenges persist: large undiagnosed populations, regional disparities, inadequate healthcare worker knowledge, and inequities affect at-risk groups. Achieving elimination by 2030 will require accelerated case-finding, broader access to simplified treatment, stronger risk-tailored and vaccination strategies, improved data systems, and renewed commitment.

Introduction:The overlap between chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health challenge. We investigated the impact of MASLD and metabolic comorbidity in a diverse London viral hepatitis clinic. Methods:This retrospective cross-sectional study (May 2018-Feb 2024) included adults with CHB having controlled attenuation parameter (CAP) measurements. MASLD was defined as CAP >264 dB/m plus ≥1 cardiometabolic factor (CMF). We used univariable and multivariable models to examine MASLD's relationship with liver stiffness and hepatitis B viral load (HBV VL). Results:Among 323 individuals (67% male, median age 36), most were from Black (35%) or non-white British/Irish (29%) backgrounds. Overall, 64% had ≥1 CMF, and 20% had MASLD. The CHB/MASLD group was significantly older (median 43 vs 35 years, p<0.001) with higher median alanine transaminase (35 vs 30 IU/L, p=0.02) and liver stiffness (5.3 vs 4.7 kPa, p<0.001). Following adjustment for covariates, MASLD remained significantly associated with liver stiffness (β = 0.48 kPa, p=0.03). While univariable analysis showed significantly lower HBV VL in people with MASLD (median 54 vs 417 IU/ml, p=0.004), adjusted multivariable analysis revealed no significant association between MASLD and log10 HBV VL (p=0.2). Conclusions:Although adjusted analysis does not support an independent association between MASLD and HBV VL, the data highlight a substantial cardiometabolic burden in this CHB population and clearly link MASLD to more severe liver disease. Holistic consideration of metabolic comorbidities is crucial in comprehensive CHB management.

Background Chronic viral hepatitis infections (hepatitis B (HBV), C (HCV) and D viruses (HDV)) are responsible for over 1 million deaths annually, due to cirrhosis and liver cancer. Mongolia has a high prevalence of all these infections, resulting in the highest incidence and mortality from liver cancer in the world. Other factors, such as metabolic dysfunction-associated steatotic liver disease (MASLD) can impact viral hepatitis, although the interaction is not fully understood. Several successful viral hepatitis screening programmes have been carried out among Mongolians living in Spain, USA, and Sweden. Protocol We describe a community-informed protocol for the implementation of liver health screening among Mongolians living in London (UK), designed by a multi-disciplinary team. This observational, mixed-methods study (‘Hep-MoLo’) has three domains. (i) In the clinical domain, liver screening events will be held in London, in collaboration with the Mongolian Community Organisation. An awareness-raising educational component will precede point-of-care screening for blood-borne infections (HBV, HCV, HIV), liver fibrosis and steatosis, and screening for cardiometabolic risk factors (obesity, hypertension, dyslipidaemia, diabetes); (ii) Laboratory studies will focus on the interaction between HBV and MASLD; (iii) A qualitative approach will be used to explore community views on liver health screening, access and engaging in care. Discussion This protocol provides a framework for a public health intervention targeting a high-risk population, combined with laboratory and qualitative research to give a multi-dimensional insight into viral hepatitis and liver health in the London Mongolian community. This is a community-academic-clinical partnership, fostering collaboration to generate data to inform clinical and public health interventions.

Introduction:Markers of liver and metabolic disease have not been well described for many populations in Africa, but could be important to inform individual and public health interventions that reduce morbidity and mortality. Methods:We studied longitudinal data from a population in rural Uganda, aiming (1) to describe trends in liver function tests and (2) to investigate how liver, metabolic and cardiovascular parameters are associated with all-cause mortality. Demographic and laboratory data were collected through the General Population Cohort in South-Western Uganda. We summarised cohort characteristics at baseline using descriptive statistics and used univariable and multivariable Cox proportional hazards models to investigate factors associated with adjusted HR (aHR) for death over a 12-year period (between 2011 and 2023). Results:Our dataset includes 7896 individuals, of whom 4441/7896 (56%) were female and 5722/7896 (72%) were aged under 45 years. Prevalence of hepatitis B virus (HBV) was 216/7896 (2.74%; 95% CI 2.38% to 3.10%) and HIV was 582/7896 (7.37%; 95% CI 6.79% to 7.94%). Alanine aminotransferase (ALT) was elevated in 2020/7896 (25.58%; 95% CI 24.62% to 26.55%). During the period observed, all-cause death was associated with older age (p<0.001), male sex (aHR 1.56, 95% CI 1.30 to 1.86) and HIV infection (aHR 1.67, 95% CI 1.25 to 2.22). Mortality was associated with an increase in aspartate aminotransferase:ALT ratio (aHR 1.17, 95% CI 1.08 to 1.26), a marker of alcoholic hepatitis. Increases in systolic blood pressure and haemoglobin A1c were also associated with significantly elevated hazards of death. Under sensitivity analysis restricted to participants with longitudinal follow-up data (n=871), HBV infection was associated with death (aHR 5.38, 95% CI 2.01 to 14.42). Conclusions:Simple interventions to prevent, diagnose and treat hypertension, diabetes, alcohol excess, and HIV and HBV infection could have an important impact on mortality in this setting.

OBJECTIVES:To assess global disparities in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomic surveillance and to develop an integrated platform that links genomic data with epidemiological burden. STUDY DESIGN:Retrospective observational analysis. METHODS:We reviewed existing viral genomic repositories to identify structural and analytical limitations. Subsequently, we integrated 10 996 HBV and 3533 HCV whole-genome sequences (WGS) from public databases with Global Burden of Disease (GBD) estimates to quantify inequities in genomic surveillance across countries and genotypes. Using these data, we developed the open-access Hepatitis Dashboard, incorporating >14 000 sequences from 141 countries with GBD metrics to evaluate representativeness and sequencing coverage relative to disease burden. RESULTS:Marked inequities in hepatitis genomic surveillance were identified. Despite increasing HBV- and HCV-associated mortality, virus sequence availability remains geographically and genotypically skewed-dominated by China and the United States, with substantial underrepresentation of HBV genotype E and HCV genotypes 5 and 8. Many high-endemic countries in Africa and the Western Pacific remain severely undersampled. We detected circulating antiviral drug-resistance mutations and developed a burden-adjusted sequencing coverage metric, revealing that several high-burden countries, including China, Nigeria and India, are among the least represented in global genomic datasets. Projections to 2030 indicate that neither HBV nor HCV are currently on track to meet WHO elimination targets. CONCLUSIONS:The Hepatitis Dashboard provides an integrated, continuously updated resource that links genomic and epidemiological data to quantify and visualise global surveillance gaps. This analysis highlights a critical disconnect between sequencing efforts and public health needs, which may limit the effectiveness of surveillance-informed strategies to support progress toward WHO 2030 elimination goals. By enabling burden-adjusted prioritisation and longitudinal tracking of genomic coverage, the platform supports evidence-based sampling strategies, equitable resource allocation, and monitoring of global progress toward hepatitis elimination.

Viral hepatitis poses a major individual and public health problem among vulnerable migrant and refugee populations in Europe. Migrants constitute a ‘key population’ for viral hepatitis elimination, and often face structural and systemic challenges, including limited healthcare access, legal barriers, stigmatization and discrimination. Their vulnerable position, together with documented high prevalence of chronic hepatitis B, C, and D in their countries of origin, place them at particularly high risk of poor health outcomes related to viral hepatitis infection. The Viral Hepatitis Prevention Board (VHPB) convened a multidisciplinary group of experts to discuss barriers to viral hepatitis prevention, diagnosis, and care in migrant populations. This open letter collates outputs from this group, focusing on important barriers and challenges to viral hepatitis prevention, screening and linkage to care for vulnerable migrant populations. It further explores strategies to improve viral hepatitis healthcare for migrants, including equitable access, expanded vaccination and screening, culturally tailored awareness campaigns, community co-production of interventions, and strengthened health systems. It also underlines the importance of sustained policy recommendations, integrating viral hepatitis services into broader health frameworks, promoting international collaboration, and leveraging innovative solutions like digital health records and community-based point-of-care testing or home sampling. Despite commitments to eliminate viral hepatitis by 2030, progress remains slow, with migrants disproportionately affected in the region. Urgent action is needed to close healthcare gaps, address inequities, ensure sustained funding, and implement coordinated efforts to protect vulnerable populations and achieve the elimination goals.

OBJECTIVES:The "EVOLVE" study set out to investigate the population prevalence of hepatitis B virus (HBV) infection, immunity, and treatment eligibility in a rural South African setting. METHODS:We tested plasma samples from 2200 participants in a population-based study in KwaZulu-Natal, of whom 50% were living with human immunodeficiency virus, for HBV surface antigen (HBsAg), HBV core antibody, and HBV surface antibody. For samples testing HBsAg-positive, we quantified alanine aminotransferase (ALT) and HBV deoxyribonucleic acid (DNA) viral load. We evaluated demographic and clinical correlates of HBV biomarkers, explored the geographical distribution of HBsAg, and assessed HBV treatment eligibility. RESULTS:Weighted HBV infection prevalence was 10.4% (95% confidence interval [CI] 9.0-12.1%). Evidence of HBV exposure and clearance was found in 34.9% (95% CI 32.4-37.5). Overall prevalence of vaccine-mediated HBV immunity was 8.9% (95% CI 7.5-10.4%), but among the subgroup born between 2000 and 2005 (after the HBV vaccine was implemented), this increased to 20.2% (95% CI 15.8-25.4). Infection prevalence was highest in the southern part of the region. Over 60% of individuals testing HBsAg-positive met treatment eligibility criteria. CONCLUSION:Prevalence of HBV in this setting is high, while vaccine-mediated immunity is low. These data highlight a pressing need for the scale-up of interventions to support progress toward elimination targets.

Abstract Chronic hepatitis B (CHB) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) are important contributors to the growing worldwide burden of liver disease. There is limited understanding regarding the interaction between CHB and MASLD. This is a consequence of the changing terminology for liver disease, inconsistent application of diagnostic tools, and poor understanding of global populations. In this review, we collate data on the use of diagnostic tests for identifying MASLD and associated liver inflammation or fibrosis in people living with CHB. We advocate for improved consensus on diagnosis, evidence-based monitoring and risk stratification, enhanced access to interventions and reduced health inequity.

BACKGROUND AND AIMS:An estimated 270 000 people in the UK live with hepatitis B infection, the leading global cause of liver cancer. In 2022, opt-out hepatitis B testing was introduced in emergency departments (ED) in London. We conducted a 2-year multicentre evaluation of this programme across seven sites. METHODS:Adults testing positive for hepatitis B surface antigen (HBsAg) through ED opt-out testing (n = 983) were compared with those referred via non-ED pathways (n = 416) over at least 12 months in the same regions with a six-month follow-up period. Demographics, clinical characteristics and factors influencing time to assessment were analysed. RESULTS:ED testing led to a 107% increase in HBV assessments. Of 983 HBsAg-positive individuals, 90.2% (887/983) were contactable and 97% (660/679) of those requiring assessment were linked to care. 35% were aware of their diagnosis but not under specialist care. Among ED-diagnosed individuals, 16.37% had significant fibrosis and 20.45% had viral loads > 2000 IU/mL. ED referrals were older (mean age 51 vs. 47 years, p < 0.001) and had lower viral loads (mean log10 HBV DNA 2.08 vs. 2.78, p < 0.001). Mean time to assessment in the ED group was 90 days. CONCLUSIONS:ED opt-out testing has doubled new assessments of hepatitis B cases, identifying individuals who would benefit from surveillance and/or treatment. Linkage-to-care rates were very high, though time to assessment was prolonged by service factors. A significant proportion were aware of their diagnosis but lost to care, underscoring the need for services which can maintain engagement.

INTRODUCTION:Treatment of hepatitis B virus (HBV) infection relies on nucleos(t)ide analogues to achieve viral suppression, with tenofovir or entecavir as first-line agents. Expanding treatment, and improving its outcomes, are crucial strategies to support progress towards global viral hepatitis elimination targets. However, therapeutic drug monitoring has not been optimized for HBV therapy. METHODS:We conducted a systematic review (PROSPERO CRD420250599139) to identify studies reporting on the relationship between drug concentrations and treatment outcomes of HBV in English from PubMed, Scopus and Web of Science. Primary search included people living with HBV, with or without HIV coinfection, treated with tenofovir and/or entecavir, with drug concentrations measured and linked to treatment outcome. RESULTS:Six studies were identified, of which five reported on HIV/HBV coinfection, and one on HBV monoinfection. Across studies, tenofovir concentrations >800 fmol/punch in dried blood spots were typically associated with viraemic suppression for both HIV and HBV. Evidence suggests that higher tenofovir concentrations (e.g. 1000-1500 fmol/punch) may be required for consistent HBV suppression. DISCUSSION:A therapeutic threshold cannot currently be defined for concentrations of tenofovir or entecavir in HBV. Larger cohort studies focusing on HBV monoinfection are needed to define therapeutic drug thresholds to optimize personalized care for people living with HBV.

Background: Hepatitis B virus (HBV) infection is endemic in many African populations, but has been neglected by funding, education, clinical infrastructure and research. High-profile international targets have been set for HBV elimination by 2030. Objectives: We here present the protocol for EVOLVE-HBV, an interdisciplinary study based at the Africa Health Research Institute aiming to quantify and characterize HBV infection in the KwaZulu-Natal (KZN) province, South Africa. The study aims to develop insights into HBV by assessing population knowledge, epidemiology, clinical features and laboratory characteristics, with the overall aim of enhancing local care pathways. Design: Study phase I is a retrospective, observational cross-sectional assessment of HBV sero-epidemiology. Phase II incorporates the prospective recruitment of adults living with HBV and HBV-negative controls from the same community. Study dates are 1 August 2023 to 31 July 2027. Methods: The study is supported by an active programme of community engagement. Phase I: banked samples are tested for HBV serum markers in a clinical diagnostic laboratory and analysed to generate weighted estimates of HBV infection, exposure and immunity. Phase II: data are collected through questionnaire, clinical assessment, biometric data, imaging using Fibroscan™ and laboratory assays including measurement of biomarkers, antiviral drug concentrations and HBV whole genome sequencing. Social scientists collect qualitative data regarding beliefs, experiences and needs of the community. Data across all themes inform a detailed picture of the sociodemographic, clinical and molecular characteristics of HBV infection. Ethics: EVOLVE-HBV is approved by the University of KZN Biomedical Research Ethics Committee in South Africa (ref. 00004495/2022), and University College London (UCL) ethics committee in the United Kingdom (ref. 23221/001). Discussion: This protocol describes a study that will inform insights into local HBV epidemiology, determine the need for scale-up of vaccination, screening and treatment, inform local policy, education and service-development and provide an evidence-based foundation for future clinical practice and translational research. Collectively, this work aims to inform improvements in clinical and public health strategies to support progress towards 2030 targets.