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Research round-up: hepatitis B

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Nature 603 , S66-S67 (2022)

doi: https://doi.org/10.1038/d41586-022-00822-z

This article is part of Nature Outlook: Hepatitis B , an editorially independent supplement produced with the financial support of third parties. About this content .

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Research Article

A systematic review of Hepatitis B virus (HBV) prevalence and genotypes in Kenya: Data to inform clinical care and health policy

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Writing – original draft

Affiliations Nuffield Department of Medicine, Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom, Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Headley Way, Oxford, United Kingdom

Roles Formal analysis, Methodology, Writing – review & editing

Affiliation Nuffield Department of Medicine, Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom

Roles Investigation, Writing – review & editing

Affiliation CA Medlynks Clinic and Laboratory, Nairobi, and Fountain Projects and Research Office, Fountain Health Care Hospital, Eldoret, Kenya

Affiliations KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya, Department of Biochemistry and Biotechnology, Pwani University, Kilifi, Kenya

Roles Formal analysis, Methodology, Supervision, Writing – review & editing

Contributed equally to this work with: Philippa C. Matthews, Anthony O. Etyang

Roles Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Writing – review & editing

* E-mail: [email protected]

Affiliations Nuffield Department of Medicine, Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom, The Francis Crick Institute, London, United Kingdom, Division of Infection and Immunity, University College London, London, London, United Kingdom, Department of Infectious Diseases, University College London Hospital, London, London, United Kingdom

Roles Conceptualization, Investigation, Supervision, Writing – review & editing

Affiliation KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya

• Louise O. Downs, 
• Cori Campbell, 
• Paul Yonga, 
• George Githinji, 
• M. Azim Ansari, 
• Philippa C. Matthews, 
• Anthony O. Etyang

• Published: January 31, 2023
• https://doi.org/10.1371/journal.pgph.0001165
• See the preprint
• Peer Review
• Reader Comments

The aim of this systematic review and meta-analysis is to evaluate available prevalence and viral sequencing data representing chronic hepatitis B (CHB) infection in Kenya. More than 20% of the global disease burden from CHB is in Africa, however there is minimal high quality seroprevalence data from individual countries and little viral sequencing data available to represent the continent. We undertook a systematic review of the prevalence and genetic data available for hepatitis B virus (HBV) in Kenya using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 checklist. We identified 23 studies reporting HBV prevalence and 8 studies that included HBV genetic data published in English between January 2000 and December 2021. We assessed study quality using the Joanna Briggs Institute critical appraisal checklist. Due to study heterogeneity, we divided the studies to represent low, moderate, high and very high-risk for HBV infection, identifying 8, 7, 5 and 3 studies in these groups, respectively. We calculated pooled HBV prevalence within each group and evaluated available sequencing data. Pooled HBV prevalence was 3.4% (95% CI 2.7–4.2%), 6.1% (95% CI 5.1–7.4%), 6.2% (95% CI 4.64–8.2) and 29.2% (95% CI 12.2–55.1), respectively. Study quality was overall low; only three studies detailed sample size calculation and 17/23 studies were cross sectional. Eight studies included genetic information on HBV, with two undertaking whole genome sequencing. Genotype A accounted for 92% of infections. Other genotypes included genotype D (6%), D/E recombinants (1%) or mixed populations (1%). Drug resistance mutations were reported by two studies. There is an urgent need for more high quality seroprevalence and genetic data to represent HBV in Kenya to underpin improved HBV screening, treatment and prevention in order to support progress towards elimination targets.

Citation: Downs LO, Campbell C, Yonga P, Githinji G, Ansari MA, Matthews PC, et al. (2023) A systematic review of Hepatitis B virus (HBV) prevalence and genotypes in Kenya: Data to inform clinical care and health policy. PLOS Glob Public Health 3(1): e0001165. https://doi.org/10.1371/journal.pgph.0001165

Editor: Abraham D. Flaxman, University of Washington, UNITED STATES

Received: May 31, 2022; Accepted: November 28, 2022; Published: January 31, 2023

Copyright: © 2023 Downs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All the data pertinent to the submission are included in the paper and its citations.

Funding: LD is funded by a Wellcome Clinician PhD fellowship (Grant number BST00070). CC is funded by GlaxoSmithKline (GSK) and the University of Oxford Nuffield Department of Medicine. PCM is funded by Wellcome (ref 110110Z/15/Z), UCL/UCLH NIHR Biomedical Research Centre (BRC) and core funding from the Francis Crick Institute. MAA is supported by a Sir Henry Dale Fellowship jointly funded by the Royal Society and Wellcome (ref 220171/Z/20/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CC is partially funded by GlaxoSmithKline. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction

Chronic hepatitis B (CHB) accounts for an estimated 90,000 deaths annually across West, East and Southern Africa, where most countries are of medium to high prevalence for CHB (prevalence ≥4%), accounting for around 20% of the worldwide burden of infection [ 1 ]. The World Health Organisation’s (WHO) point prevalence estimate of CHB for Africa is 6.1% (95% CI 4.6–8.5%), but this varies substantially between settings, and high-quality data for individual countries are scarce [ 1 ]. CHB meets many of the WHO criteria for a neglected tropical disease, including disproportionately affecting populations living in poverty, being associated with significant stigma and discrimination, and poor investment in clinical infrastructure and research [ 2 ]. Fewer than 10% of people have access to testing and treatment, leading to delayed diagnosis, with associated risks of advanced liver disease including hepatocellular carcinoma (HCC) [ 1 ].

The Global Health Sector Strategy (GHSS) for viral hepatitis aims to eliminate HBV as a public health threat by 2030 by reducing the incidence of new chronic infections by 90% and reducing mortality by 65% from the 2015 baseline to achieve the 2030 WHO Sustainable Development Goals [ 3 ]. These are ambitious targets, and current estimates indicate they will not be attained in most settings until beyond 2050 [ 4 ]. Detailed seroprevalence data are lacking, but are urgently needed to target testing, treatment, and prevention interventions to the highest risk groups, to allocate resources, and to inform policy.

In Kenya, there is limited information regarding HBV prevalence. Most studies focus on specific groups such as blood donors and those living with HIV, which may not be representative of the general population [ 5 – 7 ]. Other studies have stringent inclusion criteria, meaning important demographic subgroups remain uncharacterised [ 8 ]. HBV testing is not done routinely in Kenya, even in antenatal populations.

Triple HBV vaccine from the age of 6 weeks onwards is recommended by the Kenyan Ministry of Health as a component of the multivalent vaccines rolled out by GAVI within the WHO Expanded Programme for Immunization (EPI). Hep B birth-dose (BD) vaccine for all babies within 24 hours of birth is recommended by the WHO, but has not been adopted by many countries–including Kenya–due to economic and logistical challenges [ 9 ]. However, more data are needed to underpin evidence-based policy in this domain, and there is increasing focus on PMTCT as part of ‘triple elimination’ strategies for HBV/HIV/Syphilis [ 10 ].

HBV is divided into 9 genotypes (A-I) with a 10 th putative genotype J [ 11 , 12 ]; these tend to have distinct geographical locations and have been linked to different outcomes. Genotype A predominates in many African countries and has been associated with horizontal transmission, chronicity, early HBeAg seroconversion [ 13 ], cirrhosis and HCC development [ 14 ]. Genotype also affects response to treatment (including drug resistance), and thus may influence clinical recommendations [ 13 – 15 ], though is not yet widely undertaken in clinical practice in most settings. Most studies of the impact of HBV genotype have been in Asia and Europe. There is a paucity of data on circulating genotypes and subgenotypes in Africa, including Kenya. Whole genome sequencing (WGS) of HBV in Kenya could provide information on transmission networks, disease and treatment outcomes, drug resistance and vaccine escape.

We here assimilate data to describe the seroprevalence and molecular characteristics of HBV infection in Kenya to underpin an evidence-base for local strategies for intervention, and highlight knowledge gaps to inform research. High resolution local data will be essential for development of local clinical care pathways and public health policy, to underpin progress towards the 2030 elimination targets.

Ethics statement

No ethical approval was required for this study.

Search strategy

We set out to review literature on prevalence and genetic characteristics of HBV infection in Kenya, using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 statement checklist ( S1 PRISMA Checklist ). We searched the online databases PubMed, Embase, African Journals Online (AJOL) and Scopus on 6 th December 2021 using the terms in Table 1 . We included studies published in English, from 2000 to December 2021 (from 2003 for AJOL) that investigated prevalence, genotype and sequencing of HBV infection in Kenya. We only included data for adults from studies for which the full text was available. There was no minimum number of participants for studies included. We initially screened using a thorough review of the title and abstract, and subsequently reviewed the full manuscripts of eligible articles. Articles that did not meet the inclusion criteria were excluded. Any uncertainty regarding the inclusion of papers was discussed with another reviewer and a consensus obtained.

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https://doi.org/10.1371/journal.pgph.0001165.t001

From each study, we extracted:

• Total number of individuals tested for HBV.
• Number of individuals found to be infected with HBV (either HBsAg positive or HBV DNA positive)
• Study location (city or geographical region)
• Participant selection criteria
• Laboratory methods for confirmation of HBV infection
• Whether any viral sequencing was undertaken, methods used and results (including genotype, presence of vaccine escape and drug resistance mutations).

Study heterogeneity and HBV risk groups

On the grounds of significant heterogeneity in the populations represented, we divided studies a priori into four groups representing populations with differing risks of testing positive for HBV infection. The low-risk group included studies likely to be most representative of the general population (antenatal women, healthcare workers, blood donors and the national survey). The moderate risk group consisted of studies containing populations living with HIV. High-risk groups were defined as people with risk factors for acquisition of blood-borne virus infection, including people who inject drugs, men who have sex with men (MSM) and sex workers. Those presenting to hospital with hepatitis or jaundice were defined as a very high-risk group, as HBV infection is enriched in populations presenting with established liver disease, particularly if the background population has medium or high HBV prevalence. This risk stratification system is a pragmatic approach to a highly heterogenous literature and we have used these risk groups for ease of reference throughout this review.

Quality assessment of studies

A thorough assessment of the study quality was done using the PRISMA guidelines [ 16 ] and Joanna Briggs Institute critical appraisal checklist for prevalence studies ( S1 Table ) [ 17 ]. Any dispute surrounding study quality was discussed with another reviewer and a consensus reached.

Identifying and analysing full-length HBV sequences from Kenya

We downloaded all full genome HBV sequences from Kenya in GenBank on 1-December-2021 to assimilate a reference set of all whole genome sequences representing Kenya. Sequences were aligned with available HBV reference sequences for each genotype (11) using MAFFT [ 18 ]. A maximum likelihood phylogenetic tree with bootstrap replicates of 1000 was created using NGPhylogeny.fr [ 19 ].

Statistical analysis

Occult HBV infection

Occult HBV infection (OBI) is defined as detectable HBV DNA in the absence of HBsAg. Where studies reported both HBsAg positivity rates and OBI rates in those who were HBsAg negative, only prevalence data based on HBsAg positivity was included in the meta-analysis, in order to ensure datasets were comparable between studies.

(i) Identification of studies

We identified 272 published studies, of which 23 studies met the inclusion criteria for prevalence assessment, representing a total of 11,467 people ( Fig 1 and Table 2 ). Three of these studies also screened individuals for occult HBV infection (OBI) in a total of 666 people using HBV DNA polymerase chain reaction (PCR) in addition to testing for HBsAg seroprevalence. Two studies screened initially with HBsAg, then with HBV DNA PCR on those who were HBsAg negative [ 20 , 21 ]. A further study included two different populations: a) those attending a clinic for sex workers, whom they screened initially for HBsAg, then HBV PCR in those who were HBsAg negative and b) known HBsAg negative, jaundiced participants whom they screened with HBV DNA PCR to detect OBI [ 22 ].

(AJOL: African Journal Online). All eight studies included for genetic analysis contain information on HBV genotype. Figure created in Biorender.com with licence to publish.

https://doi.org/10.1371/journal.pgph.0001165.g001

https://doi.org/10.1371/journal.pgph.0001165.t002

We identified nine studies reporting HBV sequence data (full or partial genome), including seven studies from among the 23 seroprevalence studies described above ( Table 2 ), and an additional two studies that only included HBsAg positive participants so were not included in prevalence analysis [ 23 , 24 ]. One study did not clearly report how many HBV samples were sequenced or the genotyping results, and this study was excluded from further analysis [ 25 ]. Eight studies remained for analysis representing 247 individuals ( Table 2 ).

We identified eight studies reporting HBsAg prevalence in low-risk populations (total number of individuals = 6828), seven studies in people living with HIV (medium risk, total number of individuals = 1861), five studies in high-risk groups (total number of individuals = 2221) and three studies in people presenting to clinical services with established liver disease (defined here as very high-risk for HBV infection; total number of individuals = 492).

(ii) Geographical distribution of HBV seroprevalence data

Of the 23 studies included, 14 (61%) were in Nairobi or Mombasa, Kenya’s most populous cities ( Table 2 ), and all studies were done in the South of the country along the infrastructure routes between Mombasa, Nairobi and Kisumu. These are also the most densely populated Kenyan counties [ 48 ]. Kisumu was the city most represented in the studies by overall sample size ( Fig 2 ).

Data from a systematic review of papers reporting prevalence and genetic data for HBV in Kenya between 2000 and 2021. The size of the red circle indicates numbers screened in each location, studies in the same location are grouped together. n = number of individuals reported. Surrounding countries are marked in blue, Kenya’s four most populous cities are marked in black. Figure created using R version 4.2.0, packages ggmaps version 3.0.0, ggplot2 version 3.3.6 and sf version 1.0–7. The Kenyan county shapefiles were obtained from the Humanitarian Data Exchange, available open source from https://data.humdata.org/dataset/geoboundaries-admin-boundaries-for-kenya .

https://doi.org/10.1371/journal.pgph.0001165.g002

The mean cohort sample size was 599 participants (IQR 434). 14 studies recruited participants for cohort inclusion at outpatient clinics (8 in HIV clinics, 4 in blood donor clinics, 1 in a health clinic and 1 in antenatal clinic), one captured data through the blood donor registry, three undertook community outreach screening, three recruited hospital inpatients, one recruited healthcare workers and one was a national survey of urban and rural population groups ( Table 2 ).

(iii) Quality assessment of the literature

Overall the quality of studies investigating HBV prevalence in Kenya was low ( Fig 3 and S1 Table ). 17/23 studies were cross sectional, reporting HBV population prevalence at a single time point only. Most cohort sampling methods were non-randomised and only 4/21 studies detailed their sample size calculation [ 20 , 21 , 37 , 41 ]. Several studies sampled people only from small geographical locations or from a subset of the general population e.g. HIV negative individuals. 21/23 studies used either an enzyme linked immunosorbent assay or chemiluminescent enzyme immunoassay (ELISA or CLEIA) for HBsAg diagnosis. Two studies used reverse passive haemagglutination for diagnosis of CHB, a method previously demonstrated to have poor sensitivity [ 26 , 27 , 43 ] ( Table 2 ). 2/23 studies went on to screen the HBsAg negative population for HBV DNA via PCR [ 20 , 21 ] and one study included a known HBsAg negative population which they screened for HBV DNA [ 22 ].

This is stratified by number of participants, study design, sampling method, data collection and diagnostic methods. RCT: Randomised controlled trial; EIA: Chemiluminescent enzyme immunoassay; ELISA: Enzyme linked immunosorbent assay.

https://doi.org/10.1371/journal.pgph.0001165.g003

(v) HBV prevalence estimates in different risk groups

The pooled estimate for HBV prevalence using a random effects model in the low-risk group was 3.36% (95% CI 2.67–4.21%) compared with 6.14% in the moderate risk group (95% CI 5.08–7.41%), 6.18% (95% CI 4.6–8.19%) in the high-risk group and 29.19% (95% CI 12.15–55.14%) in the very high-risk group, however we note that the confidence interval of this estimate is very wide ( Fig 4 ). Heterogeneity was significant (I 2 > 50%) within each subgroup, and highest in the very high-risk sub-group (I 2 = 95%, p < 0.01).

Data generated through a systematic review reporting prevalence and genetic data for HBV in Kenya between 2000–2021. In each case, the size of the population included is represented by the size of the square. Point prevalence and 95% Confidence Interval (CI) is indicated for each study. Studies are ordered by HBV prevalence in each risk group.

https://doi.org/10.1371/journal.pgph.0001165.g004

Three studies screened for OBI using HBV DNA PCR. These were in populations known to be HBsAg negative and from different HBV risk groups: blood donors, those living with HIV and those presenting to hospital with jaundice. OBI prevalence estimates in these studies were 2.4%, 5.3% and 18.7% respectively [ 20 – 22 ].

(vi) Identification of HBV sequences

All eight studies including HBV genetic information used PCR of the HBV basal core promotor, Pol or S genes for amplification, followed by Sanger sequencing to determine genotype. Two studies looked for known drug resistance-associated mutations (RAMs) [ 23 , 24 ]. Two studies undertook whole genome HBV sequencing in a total of 22 patients [ 23 , 28 ]. 228/247 (92%) of participants were infected with HBV genotype A, 15/247 (6%) with genotype D infection, whilst the remaining were either mixed genotype populations (2/247) or genotype D/E recombinants (2/247) ( Table 3 ). Sub-genotype was determined in 146/247 (59%) participants. This was most commonly sub-genotype A1 (134/146, 92%) in keeping with previous regional data [ 44 ].

Data from 8 studies marked * in Table 2 .

https://doi.org/10.1371/journal.pgph.0001165.t003

To provide further background context for HBV sequences in Kenya, we identified 25 full length HBV sequences from GenBank ( Fig 5 ). These were generated from three studies, published in 2013, 2015 and 2016 [ 24 , 28 , 45 ]. They primarily represented individuals presenting to hospital with jaundice (21/25 sequences), infected with genotypes A1 and D.

Kenyan sequences are those published in GenBank (downloaded 1 st Dec 2021) and are shown in red alongside genotype reference sequences in black (1000 bootstrap replicates were performed, and bootstrap support of ≥70% are indicated. Reference sequences from McNaughton et al. (2020) [ 11 ].

https://doi.org/10.1371/journal.pgph.0001165.g005

5/8 studies provided a detailed analysis of either amino acid or nucleotide substitutions found in the sequenced region of HBV [ 20 , 23 , 24 , 33 , 37 ]. 2/5 studies correlated these with known drug resistance mutations to lamivudine and other nucleoside analogues ( Table 4 ) [ 20 , 33 ]. One study reported the emergence of drug resistance mutations during lamivudine treatment associated with breakthrough HBV viraemia [ 33 ]. Multiple other mutations were described in the five studies, some of which were in the major hydrophilic region of the surface gene, and thus potentially important in influencing both natural and vaccine-mediated immunity [ 46 , 47 ].

https://doi.org/10.1371/journal.pgph.0001165.t004

(vi) HBV serology and HBV biomarkers

Exploring the prevalence of anti-HBs (vaccination or exposure) and anti-HBc (exposure to HBV) in HBsAg-negative populations is important to build up a full picture of population epidemiology. Among individuals testing HBsAg-positive, a panel of biomarkers is used to determine treatment eligibility, including HBeAg status, HBV DNA viral load, liver enzymes and imaging scores. These parameters are outside the primary scope of this study, but the data can be accessed as a supporting data file [ 48 ].

Enhanced efforts to characterise the epidemiology and disease burden of HBV are urgently required in Africa, as HBV is present at medium to high endemicity in many populations but has been neglected as a public health problem. Here we have reviewed the literature available on prevalence, genotypes and drug resistance data for CHB in Kenya. In our ‘low-risk’ category, intended to provide estimates most reflective of the general population, the pooled prevalence estimate for HBV infection was 3.4%. Point-prevalence estimates of ~6% were obtained for the groups we defined as medium and high risk, comprising people living with HIV infection and those with other identified risk factors for blood-borne virus infection. Similar prevalence estimates in the moderate- and high-risk groups was only evident after analysis. The number of studies was too low to allow for further subdivision into individual risk groups (e.g. comparing people who inject drugs, MSM, and sex workers). In the population presenting to healthcare facilities with established symptomatic liver disease (classified here as ‘very high risk’), the prevalence of HBV was 29.2% (although the underlying primary risk factor(s) for HBV acquisition in this group are not established).

In this very high-risk group, wide confidence intervals along with significant heterogeneity (I 2 = 95%) are notable. This population evidently has very different pre-test probabilities for HBV infection depending on underlying risk factors. In the absence of robust screening programmes, many people do not find out they have HBV infection until presenting to hospital with manifestations of liver disease. While the prevalence in this group evidently cannot be extrapolated to the general population, it is nevertheless an important observation that HBV in this setting accounts for such a high proportion of end-stage liver disease. Furthermore 2/3 studies in this very high-risk group used RPHA for HBsAg detection which is less sensitive than HBsAg, and therefore may underestimate true prevalence of HBV infection.

Most studies included in this review focussed on specific groups of people such as blood donors and those co-infected with HIV. Blood donation in Kenya is voluntary and often done by family members of those in need. There is no financial compensation for donation [ 49 ]. Routine screening for HBV through the Kenyan National Blood Transfusion Service (KNBTS) consists of ELISA for HBsAg only and there is no nucleic acid amplification testing (NAAT); some OBI may therefore go unidentified. Only one study in this review focussed on pregnant women [ 37 ] and one study enrolled healthcare workers [ 41 ]. These are accessible and important groups to screen for HBV infection given they are engaged with healthcare, likely to come for follow up visits, and interventions can have a significant impact on reducing transmission events. Treatment for pregnant mothers and healthcare workers would reduce onward transmission, and vaccination uninfected healthcare workers and babies at birth would decrease the overall burden of infection, reducing morbidity and mortality. One study was nationwide [ 38 ], but only included those who were HIV negative. More general population screening is lacking, and testing is not routinely done when presenting to healthcare facilities [ 50 ]. Some areas of Kenya have been more rigorous in their diagnostic approaches, but this is sporadic and may be increased only when there is a known outbreak of HBV in the local community, as has been the case in other African countries [ 51 , 52 ]. This may give a skewed view on population prevalence, but also leads to missed opportunities for diagnosis and intervention, particularly given the very high proportion of those presenting to hospital with jaundice or hepatitis found to be infected with HBV (pooled HBV prevalence 29.19% and 18.7% OBI prevalence).

It is notable that no studies were done in Northern Kenya, particularly along the borders with Somalia and South Sudan where the prevalence of HBV is likely to be substantially higher (for these two neighbouring countries, HBsAg prevalence is estimated at 19% and 12% respectively [ 53 , 54 ], however population density here is also very low [ 55 ].

Along with minimal population screening, there is very little sequencing of HBV in Kenya. Among the 25 papers we reviewed regarding HBV sequencing, only two reported whole genome sequencing, and none did next generation sequencing. We identified only 25 complete HBV genomes from Kenya in a GenBank search. Most available data is from single gene PCR and Sanger sequencing of S and P genes to determine genotype. Expanding these data will allow identification of recombinant genotypes, of which there is evidence in Kenya [ 28 , 31 ], but currently without good understanding of how these translate into clinical outcomes. Deep sequencing data will enable detection of minority variant mutations that may be relevant in emergence of vaccine escape and drug resistance, and also allow description of viral quasispecies, how this correlates with clinical phenotype and other biomarkers.

Three studies reviewed here screened for OBI using PCR. OBI prevalence was similar to estimated pooled HBsAg prevalence in the associated risk group (2.4%, 5.3% and 18.7% OBI prevalence in low, medium and high/very-risk groups compared with 3.36%, 6.14% and 6.18/29.19% pooled HBsAg positivity estimates in the equivalent groups). This indicates that many HBV cases are being missed due to the lack of appropriate screening tests, however the cost and poor availability of HBV DNA testing means it is not currently feasible to use as a universal screening test in Kenya. 20/23 studies solely reported HBsAg positivity diagnosed using other less sensitive tests. It is worth noting that of those presenting to hospital with jaundice who were HBsAg negative, nearly 20% were HBV DNA positive. It is not known whether the jaundice was due to acute HBV infection, or reactivation of chronic disease, but it seems to be an important indicator of HBV infection and screening of all those presenting to hospital with jaundice or hepatitis for OBI with HBV DNA PCR would be optimal. Few studies had characterised HBV exposure and vaccination status using anti-HBc and anti-HBs respectively. This highlights a broader issue around funding and access to laboratory tests needed for complete epidemiological assessment of populations.

HIV coinfection as a special case

The prevalence of HIV infection in adults in Kenya is 4.2% (95% CI 3.7–4.9%) [ 56 ]. Seven studies included in this analysis reported HBV prevalence in people living with HIV. The pooled HBV prevalence in this group was 6.14% (95% CI 5.08–7.41%). The HIV population is better represented than other groups at risk, as HBV screening is easier to offer to individuals already accessing healthcare for HIV monitoring and treatment. Through this established infrastructure for HIV (including clinics with staff, laboratory support, blood monitoring and drug distribution services), clinical care pathways for HBV could be incorporated. Although tenofovir is available free of charge in Kenya and is on the WHO list of essential medicines [ 57 ], it is only consistently available in combination with lamivudine or emtricitabine for HIV treatment, leaving the HBV monoinfected population unable to access licensed monotherapy.

Limitations

The HBV prevalence estimates we have generated here are wide and vary significantly between the risk groups (pooled risk group prevalence 3.36% - 29.19%). The very high-risk group also has a very wide confidence interval for prevalence estimates. Our risk groups were determined a priori based on existing understanding of the distribution of HBV infection, but data were insufficient to disaggregate into more specific groups, and we recognise that the prevalence of HBV infection in populations at risk varies substantially by setting. Other sources have different estimates of Kenyan HBV prevalence (e.g. 1% by the CDA Foundation [ 4 ]). The CDA data are from 2016, so may be out of date, but the varying estimates reflect difficulties with methods of data collection, varying data sources and data missingness. The overall quality of studies was low, with non-random sample selection common, no calculation of sample size in most studies and nearly all studies being cross sectional representing only a snapshot of HBV prevalence. Only selected populations are represented by the studies we identified, and even those studies seeming to represent the population more broadly are subject to bias. For example, the study of healthcare workers was primarily female nurses [ 41 ] and the nationwide survey only included HIV negative participants [ 38 ]. We considered only including those studies reaching a certain quality threshold in the prevalence meta-analysis, however this would have substantially restricted the available data. For example, including only those studies with random sampling methods and a documented sample size calculation would have left only three studies. One of the key findings of this systematic review is the lack of good quality seroprevalence data, and detailing this gives a good understanding of available literature.

There are no data for the northern part of Kenya, including the region around the border with South Sudan where there might be migration of high prevalence populations. It is likely that prevalence of HBV infection varies significantly by age, region of the country, and according to particular at-risk groups–thus targeted surveillance is important to provide an evidence-base for local and population-specific interventions.

No children were included in this review. In 2019 Kenya achieved an average coverage of 91% of 3 rd dose HBV childhood vaccination [ 58 ], but in future studies, screening children for HBsAg, anti-HBc and anti-HBs by birth cohort would be important to determine the impact of the vaccine campaign on infection, exposure and immunity, and to identify any populations being missed by vaccine coverage. There are increasing calls for the scale-up of BD HBV immunisation as part of a triple elimination campaign.

We highlight the poor representation of HBV in Kenya with sequencing data, identifying only two studies that undertook whole genome sequencing. 24/25 sequences available on GenBank were from two studies. This is clearly not representative of HBV in the general population, and work is required to determine circulating genotypes and to characterise polymorphisms that are relevant to outcomes of infection, treatment and vaccination.

Conclusions

We have assimilated epidemiological data for HBV in Kenya, together with genetic parameters where available, to provide the most refined picture possible to date. Our data suggest that Kenya falls into the ‘intermediate’ prevalence group (2–5%, as defined by the WHO). A sparse literature highlights the pressing need for clinical and research enterprise, to provide an evidence base for realistic and practical strategies that support country-specific scale-up of screening and treatment. Alongside continued efforts for three-dose vaccine coverage in infancy, enhanced interventions may include focus on HBV birth dose vaccine as part of the triple elimination initiative, with improved access to diagnostics, surveillance and treatment, to curtail the burden of disease in those currently infected, and reduce the incidence of new infections, moving Kenya towards 2030 elimination targets.

Supporting information

S1 checklist. preferred reporting items for systematic review and meta-analysis (prisma) 2020 statement checklist..

https://doi.org/10.1371/journal.pgph.0001165.s001

S1 Table. Joanna Briggs critical appraisal checklist.

https://doi.org/10.1371/journal.pgph.0001165.s002

Acknowledgments

This manuscript was written with the permission of the Director, KEMRI-CGMRC.

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Hepatitis B

• Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.
• The virus is most commonly transmitted from mother to child during birth and delivery, in early childhood, as well as through contact with blood or other body fluids during sex with an infected partner, unsafe injections or exposures to sharp instruments.
• WHO estimates that 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections each year.
• In 2022, hepatitis B resulted in an estimated 1.1 million deaths, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer).
• Hepatitis B can be prevented by vaccines that are safe, available and effective.

Hepatitis B is an infection of the liver caused by the hepatitis B virus. The infection can be acute (short and severe) or chronic (long term).

Hepatitis B can cause a chronic infection and puts people at high risk of death from cirrhosis and liver cancer.

It can spread through contact with infected body fluids like blood, saliva, vaginal fluids and semen. It can also be passed from a mother to her baby.

Hepatitis B can be prevented with a safe and effective vaccine. The vaccine is usually given soon after birth with boosters a few weeks later. It offers nearly 100% protection against the virus.

Hepatitis B is a major global health problem. The burden of infection is highest in the WHO Western Pacific Region and the WHO African Region, where 97 million and 65 million people, respectively, are chronically infected. Sixty-one million people are infected in the WHO South-East Asia Region, 15 million in the WHO Eastern Mediterranean Region, 11 million in the WHO in the WHO European Region and 5 million in the WHO Region of the Americas.

Transmission

In highly endemic areas, hepatitis B is most commonly spread from mother to child at birth (perinatal transmission) or through horizontal transmission (exposure to infected blood), especially from an infected child to an uninfected child during the first 5 years of life. The development of chronic infection is common in infants infected from their mothers or before the age of 5 years.

Hepatitis B is also spread by needlestick injury, tattooing, piercing and exposure to infected blood and body fluids, such as saliva and menstrual, vaginal and seminal fluids. Transmission of the virus may also occur through the reuse of contaminated needles and syringes or sharp objects either in health care settings, in the community or among persons who inject drugs. Sexual transmission is more prevalent in unvaccinated persons with multiple sexual partners.

Hepatitis B infection acquired in adulthood leads to chronic hepatitis in less than 5% of cases, whereas infection in infancy and early childhood leads to chronic hepatitis in about 95% of cases. This is the basis for strengthening and prioritizing infant and childhood vaccination.

The hepatitis B virus can survive outside the body for at least 7 days. During this time, the virus can still cause infection if it enters the body of a person who is not protected by the vaccine. The incubation period of the hepatitis B virus ranges from 30 to 180 days. The virus may be detected within 30 to 60 days after infection and can persist and develop into chronic hepatitis B, especially when transmitted in infancy or childhood.

Most people do not experience any symptoms when newly infected.

Some people have acute illness with symptoms that last several weeks:

• yellowing of the skin and eyes (jaundice)
• feeling very tired
• pain in the abdomen.

When severe, acute hepatitis can lead to liver failure, which can lead to death.

Although most people will recover from acute illness, some people with chronic hepatitis B will develop progressive liver disease and complications like cirrhosis and hepatocellular carcinoma (liver cancer). These diseases can be fatal.

HBV-HIV coinfection

About 1% of persons living with HBV infection (2.7 million people) are also infected with HIV. Conversely, the global prevalence of HBV infection in HIV-infected persons is 7.4%. Since 2015, WHO has recommended treatment for everyone diagnosed with HIV infection, regardless of the stage of disease. Tenofovir, which is included in the treatment combinations recommended as first-line therapy for HIV infection, is also active against HBV.

It is not possible on clinical grounds to differentiate hepatitis B from hepatitis caused by other viral agents; hence laboratory confirmation of the diagnosis is essential. Several blood tests are available to diagnose and monitor people with hepatitis B. Some laboratory tests can be used to distinguish acute and chronic infections, whilst other can assess and monitor the severity of liver disease. Physical examination, ultrasound, fibroscan can also be performed to assess degree of liver fibrosis and scarring and monitor progression of liver disease. WHO recommends that all blood donations be tested for hepatitis B to ensure blood safety and avoid accidental transmission.

As of 2022, 13% of all people estimated to be living with hepatitis B were aware of their infection, while 3% (7 million) of the people living with chronic hepatitis B were on treatment. According to latest WHO estimates, the proportion of children under five years of age chronically infected with HBV dropped to just under 1% in 2019 down from around 5% in the pre-vaccine era ranging from the 1980s to the early 2000s.

In settings with high Hepatitis B surface antigen seroprevalence in the general population (defined as  > 2% or  > 5% HBsAg seroprevalence), WHO recommends that all adults have access to and be offered HBsAg testing with linkage to prevention and care and treatment services as needed. WHO also recommends blood donor screening, routine testing for hepatitis B all pregnant women to provide the opportunity to institute measures for prevention of MTCT as well as focused or targeted testing of specific high-risk groups (including migrants from endemic regions, partners or family members of infected persons, and health-care workers PWID, people in prisons and other closed settings, MSM and sex workers, HIV-infected persons.

There is no specific treatment for acute hepatitis B. Chronic hepatitis B can be treated with medicines.

Care for acute hepatitis B should focus on making the person comfortable. They should eat a healthy diet and drink plenty of liquids to prevent dehydration from vomiting and diarrhoea.

Chronic hepatitis B infection can be treated with oral medicines, including tenofovir or entecavir.

Treatment can

• slow the advance of cirrhosis
• reduce cases of liver cancer
• improve long term survival.

Most people who start hepatitis B treatment must continue it for life.

With the updated Hepatitis B Guidelines, it is estimated that more than 50% of people with chronic hepatitis B infection will require treatment, depending on setting and eligibility criteria.

In low-income settings, most people with liver cancer present late in the course of the disease and die within months of diagnosis. In high-income countries, patients present to hospital earlier in the course of the disease and have access to surgery and chemotherapy, which can prolong life for several months to a few years. Liver transplantation is sometimes used in people with cirrhosis or liver cancer in technologically advanced countries, with varying success.

Hepatitis B is preventable with a vaccine.

All babies should receive the hepatitis B vaccine as soon as possible after birth (within 24 hours). This is followed by two or three doses of hepatitis B vaccine at least four weeks apart.

Booster vaccines are not usually required for people who have completed the three-dose vaccination series.

The vaccine protects against hepatitis B for at least 20 years and probably for life.

Hepatitis B can be passed from mother to child. This can be prevented by taking antiviral medicines to prevent transmission, in addition to the vaccine.

To reduce the risk of getting or spreading hepatitis B:

• practice safe sex by using condoms and reducing the number of sexual partners
• avoid sharing needles or any equipment used for injecting drugs, piercing, or tattooing
• wash your hands thoroughly with soap and water after coming into contact with blood, body fluids, or contaminated surfaces
• get a hepatitis B vaccine if working in a healthcare setting.

WHO response

Global health sector strategies on, respectively, HIV, viral hepatitis, and sexually transmitted infections for the period 2022–2030 (GHSSs)  guide the health sector in implementing strategically focused responses to achieve the goals of ending AIDS, viral hepatitis (especially chronic hepatitis B and C) and sexually transmitted infections by 2030.

The GHSS recommend shared and disease-specific country actions supported by actions by WHO and partners. They consider the epidemiological, technological, and contextual shifts of previous years, foster learnings across the disease areas, and create opportunities to leverage innovations and new knowledge for effective responses to the diseases. They call to scale up prevention, testing and treatment of viral hepatitis with a focus to reach populations and communities most affected and at risk for each disease, as well as addressing gaps and inequities. They promote synergies under a universal health coverage and primary health care framework and contribute to achieving the goals of the 2030 Agenda for Sustainable Development.

WHO organizes annual World Hepatitis Day campaigns to increase awareness and understanding of viral hepatitis. For World Hepatitis Day 2023, WHO focused on the theme “One life, one liver” to illustrate the importance of the liver for a healthy life and the need to scale up viral hepatitis prevention, testing and treatment to prevent liver diseases and achieve the 2030 hepatitis elimination target.

Global hepatitis report, 2024

Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection

World Hepatitis Day

Global health sector strategy on viral hepatitis

Guidelines & manuals

• Monitoring and evaluation of hepatitis B and C
• Manual for the development of national viral hepatitis plans

More about hepatitis

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• Published: 09 August 2024

Disparities in hepatitis B virus healthcare service access among marginalised poor populations: a mixed-method systematic review

• Caixia Li 1 ,
• Dejina Thapa 2 ,
• Qian Mi 3 ,
• Yuanxiu Gao 1 &

Infectious Diseases of Poverty volume  13 , Article number:  58 ( 2024 ) Cite this article

161 Accesses

Metrics details

Marginalised poor populations, characterised by poverty and social exclusion, suffer disproportionately from hepatitis B virus (HBV) infections and encounter substantial disparities in access to healthcare. This has further exacerbated the global HBV burden and precluded progress towards HBV elimination. This mixed-method systematic review aimed to synthesise their utilisation and influencing factors in HBV healthcare services, including screening, vaccination, treatment, and linkage-to-care.

Eleven databases were searched from their inception to May 4, 2023. Quantitative and qualitative studies examining the factors influencing HBV healthcare access among marginalised poor populations were included. A meta-analysis was conducted to synthesise the pooled rates of HBV healthcare utilisation. The factors influencing utilisation were integrated and visualised using a health disparity research framework.

Twenty-one studies were included involving 13,171 marginalised poor individuals: sex workers, rural migrant workers, irregular immigrants, homeless adults, and underprivileged individuals. Their utilisation of HBV healthcare ranged from 1.5% to 27.5%. Meta-analysis showed that the pooled rate of at least one dose of the HBV vaccine barely reached 37% (95% confidence interval: 0.26‒0.49). Fifty-one influencing factors were identified, with sociocultural factors ( n = 19) being the most frequently reported, followed by behavioural ( n = 14) and healthcare system factors ( n = 11). Socio-cultural barriers included immigration status, prison history, illegal work, and HBV discrimination. Behavioural domain factors, including previous testing for sexually transmitted diseases, residential drug treatment, and problem-solving coping, facilitated HBV healthcare access, whereas hostility coping exerted negative influences. Healthcare system facilitators comprised HBV health literacy, beliefs, and physician recommendations, whereas barriers included service inaccessibility and insurance inadequacies. The biological and physical/built environments were the least studied domains, highlighting that geographical mobility, shelter capacity, and access to humanitarian health centres affect HBV healthcare for marginalised poor populations.

Conclusions

Marginalised poor populations encounter substantial disparities in accessing HBV healthcare, highlighting the need for a synergistic management approach, including deploying health education initiatives to debunk HBV misperceptions, developing integrated HBV management systems for continuous tracking, conducting tailored community outreach programmes, and establishing a human rights-based policy framework to guarantee the unfettered access of marginalised poor populations to essential HBV services.

The hepatitis B virus (HBV) is a hepatotropic DNA virus that affects nearly one-third of the global population [ 1 ]. HBV caused approximately 254 million chronic infections in 2022 [ 1 ], which was more than HIV, tuberculosis, or malaria combined [ 2 , 3 ]. The number of HBV-related deaths from HBV are projected to increase by 35% from 820,000 in 2019 to 1,109,500 by 2030 [ 4 ]. HBV persists as a substantial public health concern across global regions (e.g. Asia-Pacific and sub-Saharan Africa). The World Health Assembly has endorsed the goal of eliminating HBV, defined as a 65% reduction in mortality and a 90% decline in the incidence of hepatitis B between 2015 and 2030 [ 5 ]. To achieve this, at least 90% of patients with hepatitis B must be diagnosed, and 80% of eligible patients must be treated [ 5 ]. However, HBV elimination activities, from prevention to testing and treatment, receive insufficient attention and investment, and were only funded by 37% of countries by 2017 [ 6 ].

Health equity alongside HBV elimination is even more been neglected. HBV is unevenly distributed across societal strata, with a disproportionately higher prevalence in marginalised poor populations who experience poverty and social exclusion from economic, social, political, and cultural dimensions [ 7 ]. These groups include, but are not limited to, homeless people, disabled individuals, sanitation workers, commercial sex workers, rural-urban migrant workers, incarcerated individuals, and irregular migrants such as refugees and asylum seekers [ 8 ]. A recent meta-analysis reported an estimated HBV prevalence of 15% among sanitation workers from Asian, African, and South American regions [ 9 ], compared with approximately 4.1% in the general population globally [ 3 ]. A prevalence rate of 30.9% for HBV exposure and incidences 7 to 10 times higher for HBV prevalence have been estimated among homeless individuals from the United States [ 10 ]. The prevalence rates among sex workers were reported to be 9.2% [ 11 ] and as high as 13.6% to 60.8% in refugees from low- and middle-income countries, including Ethiopia, Thailand, and Pakistan [ 12 ]. Unstable living conditions, poor living standards, limited access to healthcare, and exposure during work (e.g. biological exposure during waste picking) create a permissive environment for HBV transmission among the marginalised poor [ 8 , 9 ].

HBV healthcare services, ranging from vaccination to screening, treatment, and linkage-to-care, are strikingly less accessible to marginalised poor populations. Only 16.7% to 38.7% of the marginalised population, including female sex workers [ 13 ], homeless individuals, and those incarcerated [ 14 ], exhibited a serological profile of HBV vaccination. More importantly, the asymptomatic nature of chronic HBV infection necessitates a reliance on screening to identify cases. However, HBV screening has been poorly utilised, with only 10.5% of those infected with HBV worldwide aware of their status, and a mere 2.2% receiving treatment in 2019 [ 1 ]. These figures are suspected to be even lower among the marginalised poor due to insufficient data capture and multiple access barriers to services, including low health literacy, competing life priorities (food, clothing, and shelter), and difficulties in accessing healthcare facilities (e.g. lack of insurance, long-distance travel, and fear of judgment by health professionals) [ 15 ]. Reports suggest that only 1.5% of underprivileged individuals living in shelters had completed HBV screening, resulting in substantial delays in HBV diagnosis and treatment [ 16 ]. As a result, marginalised poor populations suffer more complications and mortality from HBV infection compared to the general public [ 8 ].

Despite this, factors influencing HBV healthcare access among marginalised poor populations are scarcely represented and synthesised in previous research, precluding an in-depth understanding of health needs and further allocation of health resources towards HBV elimination among the population. Thus, this review was conducted to synthesise the evidence on HBV healthcare service utilisation and its influencing factors among marginalised poor populations. It was guided by the National Institute on Minority Health and Health Disparity (NIMHD) research framework, which employs an integrative approach to represent multifaceted levels (individual, interpersonal, community, and societal) and domains (biological, behavioural, physical/built environment, socio-cultural environment, and healthcare system) that collectively explain health disparities [ 17 ]. The multitude of factors will be synthesised and visualised in the NIMHD framework to inform tailored interventions, policy-making, and resource allocation towards the global HBV elimination goal.

A systematic review and meta-analysis were conducted. The protocol was registered with the International Prospective Register of Systematic Reviews (CRD42022381183).

Literature search

Following the PICOs framework, approximately 133 search terms (Supplementary material 1) were developed pertaining to population and outcomes of this review, including “marginalized poor”, “hepatitis B”, “screening”, “vaccination”, “linkage-to-care”, and “influencing factors”. Relevant synonyms (e.g. hard to reach) and medical subject-heading (MeSH) terms were identified by referencing previous literature on marginalised poor populations [ 18 ] and by conducting an initial search in MEDLINE via OvidSP.

Search terms were retrieved in the fields of “title”, “keywords”, and “abstract”. Truncations (*) and adjacency searchers (adj) were used to enhance search efficiency. The following 11 databases were searched from their inception to May 4, 2023: Embase, MEDLINE via Ovid, Ovid Emcare, Ovid Nursing Database, British Nursing Index, Ovid APA PsycInfo, Cochrane Library, CINAHL, ProQuest Health & Medicine Collection, Scopus, and China National Knowledge Internet. There were no restrictions on language or publication data. A medical librarian refined the search strategy. Detailed search records for each database are shown in Supplementary material 1.

Study screening

After removing duplicates using Covidence (Veritas Health Innovation, Melbourne, Australia), four researchers independently screened the titles and abstracts of the retrieved articles against the eligibility criteria. The full texts of potentially eligible articles were retrieved and scrutinised by pairs of researchers. Disagreements were resolved through discussion.

Inclusion and exclusion criteria

Studies were eligible if they reported factors influencing HBV healthcare access among marginalised poor populations. The ‘Participant-Intervention-Comparator-Outcomes-Study design’ (PICOs) framework [ 19 ] was followed to formulate the following eligibility criteria:

The marginalised poor, who experience poverty and social exclusion across economic, social, political, and cultural dimensions, were eligible [ 7 ]. Focusing on the specific attributes of marginalisation—low-skill levels, low-socioeconomic status, and disability—this review included the following groups of marginalised poor individuals aged ≥ 18 years: (1) homeless adults; (2) migrant workers, including migrant domestic workers, migrant farmworkers, and migrant construction workers; (3) individuals with low socioeconomic status, such as farmers, construction workers, sanitation workers, the unemployed, and those living in poverty; and (4) individuals with disabilities. However, other marginalised populations, including men who have sex with men, were outside the scope of this review, and only included migrants with low socioeconomic status. Studies that included both the marginalised poor and the general population were eligible only if a subgroup analysis of the former was performed.

Studies should report factors influencing poor marginalised populations engagement in HBV vaccination, screening, treatment, and linkage-to-care, which refers to the process of referring patients with hepatitis B to medical care, ensuring that they receive directed care and treatment and are monitored regularly [ 20 ].

Study design

Quantitative, qualitative, and mixed-methods studies were eligible if they met the aforementioned criteria. Reviews, conference abstracts, editorials, guidelines, and letters were excluded.

Data extraction

A standard data extraction form was used to extract study data, focusing on factors influencing HBV healthcare access among marginalised poor populations. Odds ratios ( OR s), 95% confidence intervals ( CI s), and P values were extracted whenever possible to identify significant influencing factors. Insignificant factors were also extracted for study comparison. Qualitative data were summarised narratively. The extracted data were checked and validated by other researchers.

Critical appraisal of methodological quality

The Mixed Methods Appraisal Tool Version 2018 was used to assess the methodological quality of the included studies [ 21 ]. Two screening items assessing the clarity of the research questions and their coherence with the collected data were applied to all included studies. Five further questions were appraised based on study types. For quantitative descriptive studies, these five questions assessed the sampling strategy, representativeness of study samples, nonresponse bias, measurements, and statistical methods. For qualitative studies, the appropriateness of the qualitative approach, qualitative data collection methods, data analysis, interpretation, and coherence between them were assessed. Each item was rated as Yes, No, or Cannot Tell. One point was given for the Yes rating and zero for the other ratings. Total scores were converted into percentage scores. Three authors independently conducted quality appraisals, and any discrepancies in ratings were resolved through discussion.

Data synthesis

Factors influencing HBV healthcare access among marginalised poor populations were integrated based on the NIMHD framework into five domains: biological, physical/built environment, behavioural, socio-cultural environment, and healthcare system. Within each domain, the influence from the individual to interpersonal, community, and societal levels was categorised and analysed whenever applicable. The STATA 18.0 (StataCorp LLC, College Station, Texas, USA) was used to conduct meta-analyses to synthesise the rate of HBV healthcare utilisation and generate the combined effects of the influencing factors. Pooled rates, OR , and 95% CI were calculated, with the significance level set at P < 0.05. Heterogeneity was evaluated using Cochrane’s Q test, with P < 0.1 indicating significant heterogeneity [ 22 ]. When heterogeneity was statistically significant, a random-effects model using the DerSimonian-Laird method was used; otherwise, a fixed-effects model was used.

Search results

The database search identified 17,172 articles (Fig. 1 ). A total of 6712 duplicates were removed, and 10,216 articles were excluded after title and abstract screening. Among the 242 full-text articles retrieved, 223 were excluded mainly because they did not entirely focus on marginalised poor populations or report factors influencing HBV healthcare utilisation. Two additional studies were included after screening the references. Ultimately, 21 studies were included in the analysis [ 16 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].

The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) diagram

Study characteristics

Nineteen quantitative descriptive studies and two qualitative studies published between 2007 and 2021 (Table 1 ) were included. More than half of these studies were conducted in the United States of America ( n = 7), Brazil ( n = 3), China ( n = 2), and France ( n = 2). The marginalised poor populations in these countries included: (1) sex workers ( n = 6); (2) rural migrant workers ( n = 2); (3) irregular, low income, and underserved immigrants ( n = 5); (4) homeless adults, parolees, and prisoners ( n = 4); and (5) underprivileged and low socio-economic status individuals ( n = 4), such as collectors of recyclable waste and roadside barbers.

Critical appraisal

With critical appraisal ratings ranging from 43% to 100%, all included quantitative ( n = 19) and qualitative ( n = 2) studies attained moderate-to-excellent methodological quality (Supplementary material 2).

The research questions were clearly stated in all the included quantitative studies, and the collected data were adequate to address the study objectives. However, the sampling strategy in five included studies may have been inappropriate to address the research question or recruit a representative sample, as convenience sampling was applied [ 37 , 39 , 41 ] or relevant information (e.g. participant recruitment and inclusion criteria) was not clearly stated [ 30 , 35 ]. Seven studies either collected self-reported HBV vaccination status [ 23 , 28 , 33 , 34 , 42 ] or did not report details regarding the reliability or validity of the applied measurements [ 31 , 37 ]. In addition, one study had a high risk of nonresponse bias (44%) [ 26 ] and six studies did not specify the number of nonrespondents [ 28 , 34 , 35 , 37 , 38 , 40 ]. In contrast, most studies had applied appropriate statistical methods, such as multivariate models, to analyse the factors influencing HBV care among the marginalised poor.

Regarding qualitative studies, one was rated as having excellent methodological quality [ 25 ] while the other had a quality assessment score of 57%, since findings were not consolidated by participant quotes, and a lack of coherence existed between data collection, analysis, and interpretations [ 36 ].

HBV healthcare utilisation among marginalised poor populations

Thirteen studies reported rates of at least one HBV vaccination dose among marginalised poor populations. A meta-analysis of the thirteen studies showed a 37% pooled uptake rate (95% CI : 0.26‒0.49, P < 0.001, I 2 = 99.3%) [ 23 , 24 , 27 , 28 , 30 , 33 , 34 , 35 , 37 , 38 , 39 , 41 , 42 ] (Fig. 2 ). Sensitivity analysis showed that the pooled rates of at least one HBV vaccination dose were not affected by the removal of any individual study (Supplementary material 2). Three studies reported HBV screening rates ranging from 1.5% to 27.5% among immigrants with low income [ 26 ], the underprivileged [ 16 ], and poor populations [ 40 ]. The rates of linkage-to-care and HBV treatment after HBV diagnoses among immigrants with low income were 0% [ 30 ] and 15.9% [ 26 ], respectively.

Forest plot of the pooled at least one-dose hepatitis B virus (HBV) vaccination rates among marginalize poor populations, applying a random-effect model

Factors influencing access to HBV healthcare services among marginalised poor populations

A total of 51 influencing factors were identified and mapped onto the NIMHD research framework (Fig. 3 ). The socio-cultural environment domain influencing factors were the most commonly reported ( n = 19), followed by behavioural ( n = 14) and healthcare system domains ( n = 11). Each included study reported individual-level influencing factors. The details are interpreted in Fig. 3 .

Factors influencing hepatitis B virus (HBV) healthcare access among marginalised poor populations mapped onto the National Institute on Minority Health and Disparities Research Framework. Note : a Immigrants with low income, migrants residing in centres for refugees and asylum seekers, irregular migrants (mainly asylum seekers), minority adults with low income, Vietnamese nail salon workers from underserved communities; b Underprivileged people living in shelters, roadside barbers and clients, collectors of recyclable waste, underserved, and residing below poverty levels; c Factors included in the National Institute on Minority Health and Health Disparity research framework but were not reported in the included studies of this review

Biological domain

Regarding biological influencing factors, perceived poor health status [ 31 , 38 ] and a history of sexually transmitted diseases, including syphilis [ 35 ] and human immunodeficiency virus [ 26 , 34 ], were associated with HBV vaccine completion and HBV treatment receipt among marginalised poor populations, including homeless adults, minority adults with low income, and female sex workers. Poor health status and experience of disease may increase awareness of health issues and care-seeking, including HBV vaccination and treatment.

Physical/built environment domain

At the individual level, geographic mobility, including moving to a different region and engaging in seasonal work, disrupted the HBV care continuum and was the main barrier to HBV vaccination and treatment among marginalised poor populations (including female sex workers and irregular migrants) [ 23 , 28 , 36 ].

At the interpersonal level, it was noteworthy that female sex workers employed in erotic show houses and clubs presented higher odds of not completing the HBV vaccination schedule compared to those working on streets, massage parlours, brothels, bars, or squares [ 24 , 28 ]. This association might be partially attributable to the higher earnings and turnover rates among women working in erotic show houses and clubs, which may induce additional barriers to vaccine completion, such as lack of time [ 28 ].

At the community and societal levels, high-capacity shelters (capacity > 160) increased the likelihood of underprivileged individuals completing HBV screening by approximately 6.4 times compared to those living in low-capacity shelters (capacity < 160) [ 16 ]. Nevertheless, those living in low-capacity shelters might have closer contact and higher risks of HBV contamination [ 16 ], necessitating additional interventions. In addition, humanitarian health centres also facilitate HBV treatment and management, especially for irregular migrants with HBV [ 36 ].

Behavioural domain

At the individual level, health behaviours and coping strategies were associated with HBV healthcare access among marginalised poor populations. Compared to inconsistent utilisation, consistent condom use was identified as a risk factor for non-completion of HBV vaccination doses among female sex workers and rural migrant workers [ 29 , 42 ]. This effect may be associated with the perception that condom use could protect against HBV, leading to a lower perceived need for vaccination. Conversely, previous testing of HBV or sexually transmitted diseases were consistently reported as a facilitator for HBV vaccination and treatment among immigrants with low income and female sex workers [ 26 , 34 ]. However, conflicting results regarding the effects of illicit drug use have also been reported. Two studies [ 33 , 34 ] found significantly higher odds of HBV vaccination among female sex workers and female prisoners with a history of injection drug use. Conversely, previous illicit or injection drugs use predicted non-completion of HBV vaccination in the combined effects in other three studies conducted among female sex workers and homeless male parolees ( OR = 1.64, 95% CI : 1.12‒2.40, I 2 = 40%, P = 0.189) (Fig. 4 a) [ 28 , 29 , 32 ].

Forest plot of the pooled odds ratio ( OR ) of influencing factors, including previous injection drug use ( a ), sex ( b ), education ( c ), and perceived HBV risk ( d ), on HBV vaccination among marginalised poor populations, applying fixed-effects models

Positive coping strategies, including problem-solving focus, were positively associated with completing the HBV vaccination series [ 35 , 38 ]. Conversely, negative emotions (e.g. hostility) were negatively associated with completion among minorities with low income, homeless adults, and male parolees [ 32 , 35 ].

At the interpersonal, community, and societal levels, female sex workers with less than one year of prostitution experience were less likely to complete HBV vaccination doses [ 24 ], suggesting a lower perceived risk of HBV infection and vaccination need compared to those with more years of prostitution [ 23 ]. Additionally, homeless adults with over 90 days of residential drug treatment were more likely to complete the HBV vaccination series than their counterparts who received less than 90 days of treatment [ 32 ]. By contrast, those attending self-help drug treatment programmes were more likely not to complete the vaccination programme compared to non-attendees [ 31 ]. Moreover, irregular migrants in Italy and France with a residence permit for medical reasons had access to free healthcare, facilitating regular HBV treatment [ 36 ].

Socio-cultural environment domain

Sociodemographic factors, including sex, race, immigration, and prison history, were common individual-level influencing factors. Among immigrants with low income and homeless adults, being male consistently predicted non-completion of the HBV vaccine series, with a combined OR value of 0.68 (95% CI : 0.54‒0.87, I 2 = 0%, P = 0.393) (Fig. 4 b) [ 26 , 31 ]. Furthermore, African Americans [ 31 , 38 ] and Asian/Pacific Islanders [ 32 ] were more likely to complete HBV vaccine doses than Caucasians. Moreover, immigration status [ 34 , 40 ], residing in host countries for less than six months [ 30 ], working illegally [ 36 ], and previous psychiatric hospitalisation [ 32 ] were negatively associated with HBV screening, lifetime vaccination, treatment, and follow-up care among underserved individuals, homeless parolees, female sex workers, and irregular migrants, such as refugees and asylum seekers. Additionally, no current or previous prison history was associated with HBV vaccination completion among homeless adults and female sex workers [ 33 , 38 ].

However, discrepancies existed between studies regarding certain demographic variables, including age, educational level, and HBV healthcare utilisation. Four studies showed that age was negatively associated with HBV screening and vaccination among rural migrant workers, collectors of recyclable waste, and underprivileged people [ 16 , 27 , 39 , 42 ]. This may be partially attributed to the national HBV vaccination plan for newborns and infants since the 1990s; younger individuals (e.g. aged 18 to 30 years) were more likely to fall within the required age for vaccination when the policy was introduced [ 42 ]. This contrasts with four other studies, in which a positive [ 29 , 31 , 41 ] or insignificant [ 38 ] correlation between age and HBV vaccination was observed. Similarly, a meta-analysis of three studies with OR values showed that a higher education level was associated with higher odds of rural migrant workers and collectors of recyclable waste undergoing HBV vaccination compared to those with a primary educational level or those with less than nine years of education ( OR = 1.64, 95% CI : 1.32‒2.03, I 2 = 0%, P = 0.544) (Fig. 4 c) [ 27 , 39 , 42 ]. However, two studies showed no correlation or a reverse correlation between educational level and HBV vaccine completion [ 24 , 38 ].

At interpersonal level, studies have yielded mixed results regarding whether social support was positively associated with HBV vaccination completion among homeless adults and parolees [ 32 , 38 ]. However, the vaccination status of family members and friends against HBV may have influenced rural migrant workers to receive the vaccination [ 42 ].

At the community and societal levels, community professional training programmes, public health campaigns, discrimination and stigma against HBV, and situational issues such as the prison realignment policy were also significant factors influencing HBV healthcare access. For example, a nail technician training programme for Vietnamese nail salon workers did not convey specific information regarding HBV and even spread misinformation by suggesting that HBV could be prevented by wearing masks [ 25 ]. In addition, owing to the knowledge gaps in HBV transmission and fears of infection, HBV discrimination and stigma (e.g. avoiding close contact with HBV-infected individuals) still exist within the community, posing another barrier to HBV care [ 25 ]. Vietnamese nail salon workers expressed that public health campaigns, including leaflets and brochures regarding HBV in nail salons, churches, and other Vietnamese communities, would be helpful in increasing HBV awareness and facilitate access to HBV vaccination [ 25 ]. Finally, among homeless male parolees, those released after the prison realignment policy were approximately 2.21 times more likely not to complete HBV vaccination compared to those released before realignment [ 32 ].

Healthcare system

At the individual level, health literacy and beliefs regarding HBV were associated with HBV healthcare utilisation among marginalised poor populations. Limited health literacy, including not having heard of HBV and misperceptions about its transmission, symptoms, and prevention strategies [ 23 , 25 ], and unawareness of the HBV vaccine, its costs, and service access [ 42 ] precluded Vietnamese nail salon workers, rural migrant workers, female sex workers, roadside barbers, and their clients from seeking HBV vaccination. Conversely, higher levels of HBV knowledge (including knowledge of HBV transmission, vaccination, and screening tests) increased the likelihood of rural migrant workers [ 42 ] and collectors of recyclable waste [ 39 ] undergoing HBV vaccination by up to 3 times.

Regarding health beliefs, a meta-analysis of two studies [ 27 , 42 ] showed that perceived HBV risk and vulnerability significantly increased the odds of rural migrant workers undergoing HBV vaccination ( OR = 1.40, 95% CI : 1.22‒1.60, I 2 = 0%, P = 0.980) (Fig. 4 d). The perceived efficacy [ 27 ] of the HBV vaccine was also associated with HBV screening and vaccination among immigrants with low income and rural migrant workers. In contrast, fear of detecting HBV, the perception of being healthy if asymptomatic [ 25 ], and HBV vaccine distrust [ 42 ] precluded marginalised poor populations from seeking HBV screening, vaccination, and care. However, the perceived severity of HBV was not significantly associated with HBV vaccination [ 27 ] and conflicting results were found regarding whether self-efficacy was positively associated with HBV vaccination completion among rural migrant workers and homeless adults [ 27 , 38 ].

At the interpersonal level, physician recommendations were essential for Vietnamese nail salon workers and irregular migrants to undergo HBV screening [ 25 , 36 ]. Otherwise, they might assume that a normal blood test would include HBV testing and perceive that they are not infected if the results were normal [ 25 ]. Moreover, receiving information about HBV vaccination programmes from healthcare professionals increased the odds of sex workers receiving at least one HBV vaccine dose by up to 4.27 times [ 23 ].

At the community level, inaccessibility [ 42 ] or inconvenience of HBV care services, including no free time and busy working hours [ 23 , 25 , 28 ], were negatively associated with HBV vaccination and care. According to Baars et al. [ 23 ], fear of needles and forgetting appointments also discouraged female sex workers from undergoing HBV vaccination [ 23 ]. Conversely, more visits to gastroenterology clinics and prior liver biopsy procedures increased the odds of immigrants with low income undergoing HBV screening and treatment by 2.6 and 5.4 times, respectively [ 26 ].

At the societal level, the cost of HBV vaccine, high out-of-pocket expenses, and lack of insurance were the main barriers to HBV vaccination and care among Vietnamese nail salon workers [ 25 ], rural migrant workers [ 42 ], and roadside barbers and their clients [ 37 ].

This mixed-method systematic review represents the comprehensive synthesis of HBV healthcare utilisation and its influencing factors among marginalised poor populations. The synthesis of 21 studies highlights a situation in which the pooled rate of HBV vaccination is merely 37%, and the rates for HBV screening, treatment, and linkage-to-care are less than 27.5%. Guided by the NIMHD research framework, 51 influencing factors were identified across biological (e.g. self-rated health status), physical/built environment (e.g. geographic mobility), behavioural (e.g. hostile coping strategy), socio-cultural environment (e.g. immigration, discrimination, and stigma), and healthcare system (e.g. health literacy and beliefs about HBV, availability, and accessibility of services) domains. These insights could inform the development of health education, HBV tracking and management systems, tailored community outreach programmes, and human rights-based policy frameworks to improve HBV healthcare access, ultimately paving the way for HBV elimination among marginalised poor populations.

The utilisation of HBV healthcare services among marginalised poor populations has been inadequately documented in the literature, with only 21 relevant studies included in this review. Reaching these populations is challenging due to logistical constraints, socioeconomic instability, and the lack of a robust healthcare infrastructure, all of which significantly impede systematic data collection and reporting [ 8 ]. According to three included studies [ 16 , 26 , 40 ], the rates of HBV screening and treatment among these populations were exceedingly low, with both less than 27.5% and 15.9%, respectively. These figures fall alarmingly short of the World Health Organization’s targets for HBV elimination, which aim for 90% diagnosis and 80% treatment coverage by 2030 [ 5 ]. Moreover, this review found that the pooled HBV vaccination rate with at least one dose was only 37%. These findings are consistent with those of a previous systematic review that revealed that referral, follow-up, and initiation of care for infectious diseases (hepatitis C virus and human immunodeficiency virus) among marginalised poor populations were below 30% [ 43 ]. These data underscore the disparities in HBV protection, diagnosis, and subsequent linkage-to-care among marginalised poor populations, all which potentially exacerbate the prevalence of HBV infection.

In the physical/built environment domain, geographical mobility emerged as a major obstacle to HBV vaccination and treatment among marginalised poor populations, especially migrant workers, irregular migrants, and female sex workers. Consistent with previous reviews, geographical mobility precluded marginalised migrant labourers from accessing health and vaccination services, leaving them more vulnerable to infectious diseases [ 44 ]. These groups often move across regions because of their illegal immigration status, seasonal working, or financial constraints [ 36 ]. The transient nature of these populations, along with their unfamiliarity with health systems in new regions, might obstruct their access to healthcare services, impede the completion of the HBV vaccine series, and lead to discontinuity in HBV care [ 23 , 28 ]. Mobility also makes it difficult to track HBV vaccination, treatment, and care requirements. This highlights that healthcare delivery and policy reform should be tailored to the circumstances of mobility among marginalised poor populations.

Regarding the behavioural domain, this review highlights the influence of negative emotional coping strategies, specifically hostility, as a barrier to HBV vaccine uptake. Consistent with previous literature, hostility is common among marginalised poor populations and creates a significant obstacle to healthcare [ 45 ]. Individuals exhibiting hostility demonstrate traits of irritation, cynicism, and mistrust, making them resistant to conforming to societal norms and complying with healthcare instructions from perceived authoritative figures, thereby complicating efforts to promote HBV vaccination [ 45 , 46 ]. The coping strategy of hostility represents a multifaceted interplay of psychological, social, cultural, and policy dynamics that perpetuate negative emotions within marginalised poor populations [ 47 ]. Severe depression, societal stereotypes (e.g. associating poverty with laziness, uncleanliness, and criminality), and discriminatory policies aimed at marginalised groups exacerbate feelings of hostility and alienation [ 48 , 49 ]. Future studies should further identify and address the complex factors that contribute to hostility among marginalised poor populations. Holistic approaches and collaborative efforts are suggested to mitigate hostility and enhance HBV vaccination among marginalised poor populations.

In the socio-cultural environment domain, migration status significantly impacts the accessibility of HBV healthcare for marginalised poor populations. Consistent with previous research [ 15 ], immigration presents a dilemma for healthcare access, particularly among immigrant sex workers [ 34 ] and irregular migrants [ 36 ]. Illegal immigration status, absence of a residence permit, unauthorised employment, fear of authorities, and discrimination for their occupations (e.g. sex work) make their access to healthcare extremely difficult [ 50 , 51 ]. Additionally, the scarcity of healthcare personnel and limited health resources allocated for irregular immigrants may further exacerbate the deficit in HBV healthcare provision [ 52 ]. Although few countries (e.g. the Netherlands and Brazil) have launched HBV vaccination programmes accessible to migrant sex workers, access to such care remains hindered by structural obstacles, including mobility and difficulties with public transportation [ 34 ]. More importantly, disruptions in federal healthcare systems obstruct HBV treatment and care for irregular immigrants relocating within the country for work [ 36 ]. Consequently, the incidence of invisible migrants infected with HBV is heightened [ 53 ]. It is imperative for governments and healthcare systems to intensify their focus on marginalised immigrant groups, promote HBV screening and vaccination services upon their arrival in host countries, and implement targeted outreach programmes to address the complex challenges in HBV treatment and care faced by these vulnerable populations.

In the healthcare system domain, significant knowledge gaps exist regarding HBV among marginalised poor populations, affecting their health beliefs and impeding their engagement with HBV screening and vaccination services [ 23 , 25 , 39 , 42 ]. Consistent with previous research [ 54 ], many lack comprehension of HBV, including its symptoms, transmission modes, and the preventive benefits of HBV vaccination. Some individuals hold misperceptions, believing that HBV spreads through food and water consumption, or mosquito bites [ 25 ]. Such misperceptions can exacerbate fear and stigmatisation linked to HBV, leading to hesitancy in seeking screening services due to apprehensions about potential stigma following a positive diagnosis [ 55 ]. Additionally, some believe that HBV transmission occurs only within families, which diminishes their perceived risk and susceptibility to HBV infection, consequently decreasing their likelihood of seeking HBV screening and vaccination [ 25 ]. Consistent with the findings of this review, previous studies have also shown that marginalised poor populations (e.g. farmers and migrants with low income) exhibit a limited understanding of HBV symptoms and often neglect or delay seeking HBV screening or treatment, even when displaying overt HBV symptoms, such as scleral jaundice [ 56 ]. Furthermore, marginalised poor populations are unaware of the existence of the HBV vaccine, lack information on where to access vaccination services, and have doubts regarding its safety and efficacy [ 42 , 54 ]. Compounded by lower levels of formal education, the population encounters challenges in accessing, comprehending, and utilising information related to HBV prevention and control [ 57 ]. It is imperative to prioritise targeted HBV education and awareness campaigns and promote immunisation outreach initiatives among marginalised poor communities.

More importantly, marginalised poor populations usually have low income and uninsured positions (e.g. roadside barbers and collectors of recyclable waste), and healthcare costs, lack of insurance coverage, and high rates of out-of-pocket payments become major deterrents to HBV healthcare access [ 25 , 42 ]. This echoes the findings of previous studies that marginalised poor populations have higher uninsured rates and are inaccessible to affordable healthcare services [ 58 , 59 ]. They might struggle to obtain basic needs (e.g. food, water, and housing), let alone access non-emergent preventive healthcare measures, such as HBV screening and vaccination [ 56 , 59 ]. Additionally, some marginalised poor populations, including nail technicians, female sex workers, and rural migrant workers, face additional challenges due to long working hours, often extending to seven days a week, making timely scheduling of HBV healthcare difficult [ 23 , 28 ]. Disparities in healthcare service access may ultimately lead to delayed HBV diagnosis, poor treatment, and diminished health outcomes, which, in turn, increase healthcare costs and financial burdens among marginalised poor populations and their families. This perpetuates a vicious cycle that further impedes access to HBV healthcare services. A more equitable health system should be established to guarantee healthcare coverage, facilitate service access, and empower supporting organisations to reduce HBV disparities among marginalised, poor populations.

This review has several limitations. First, although there was no restriction on the language of publications, this review only searched English and Chinese language databases, potentially missing relevant studies in other languages. Second, this review did not search for gray literature, including news, policy statements, and discussion forums, which could have provided valuable insights into healthcare utilisation among marginalised poor populations. Third, heterogeneity was observed in the pooled analysis of the HBV vaccination rate, which could stem from variations in study design and populations. This may have decreased the certainty of the synthesised evidence. Fourth, HBV vaccination status was self-reported in some included studies [ 23 , 28 ], potentially introducing underestimation or overestimation and biasing the estimated HBV vaccination rate in this review. Finally, the findings of this review should be interpreted with caution, considering the specific contexts of the included studies. Variations in the availability of HBV vaccinations, population demographics, and intervention approaches among the included studies may have affected generalisability of the findings.

Engagement with HBV healthcare among marginalised poor populations is poorly documented. A substantial portion of this population remains undiagnosed and untreated, exacerbating health inequities towards HBV elimination. Future empirical and modelling research is warranted to capture the missing data. Multilevel strategies addressing the social determinants that hinder HBV healthcare access are also suggested to narrow these inequities.

At the individual level, tailored health education is necessary to dispel misconceptions regarding HBV infection, including its symptoms, transmission routes, and preventive and treatment measures. To accommodate the low educational level of marginalised poor populations, utilising digital media and other technologies to disseminate engaging and easy-to-understand content is suggested to effectively reach and encourage HBV prevention and treatment behaviours. At the healthcare system level, establishing integrated HBV management systems is essential to address the challenges posed by the high geographic mobility of marginalised poor populations. Strategies include implementing mobile health clinics, telemedicine services, and online HBV surveillance platforms that allow continuous tracking and management. Incorporating HBV healthcare services into commonly accessed healthcare settings by marginalised poor populations, such as shelter-based clinics, humanitarian health centres, and drug treatment facilities, can also enhance accessibility and continuity of care. At the community level, bolstering outreach programmes for HBV screening and vaccination in venues frequented by marginalised poor populations, such as nail salons, churches, and ethnic community centres, is essential. Efforts led by community leaders and supported by non-governmental organisations to reduce hostility and stigma surrounding HBV are critical for improving programme reception and adherence. At the policy level, a human rights-based framework is suggested, especially for irregular migrants, to ensure unfettered access to crucial HBV healthcare due to their illegal immigration status. Policy adjustments should also address the right to health insurance, provide complementary HBV screening and vaccination for special groups (such as sex workers and individuals from HBV-prevalent regions), and ensure the availability of ongoing antiviral treatment.

This systematic review, employing a mixed-method methodology, comprehensively synthesised evidence regarding HBV healthcare utilisation and its influencing factors among marginalised poor populations. It identified significant service access gaps, with rates of HBV screening, treatment, and linkage-to-care alarmingly low among vulnerable populations, ranging from 1.5% to 27.5%. The pooled rate of at least one HBV vaccination dose barely reached 37%. Through the lens of the NIMHD research framework, this review identified 51 influencing factors dispersed across multiple domains: biological (e.g. self-rated health status and sexually transmitted diseases), physical/built environment (e.g. distance to health services and geographic mobility), behavioural (e.g. condom usage and hostile coping strategies), socio-cultural environment (e.g. immigration, discrimination, and stigma), and healthcare system (e.g. health literacy and beliefs about HBV, availability and accessibility of services) domains were identified to influence the HBV healthcare.

To facilitate HBV elimination among vulnerable populations, access to HBV healthcare services—from screening to vaccination, diagnosis, treatment, and follow-up care—should be enhanced. The findings of this review suggest a synergistic approach to counteracting these barriers. This would involve health education initiatives aimed at debunking HBV misperceptions, establishing integrated HBV management systems for continuous tracking and care, tailored outreach programmes geared towards improving screening and vaccination rates, and incorporating a human rights-based policy framework to guarantee unfettered access to essential HBV healthcare for marginalised poor populations.

Availability of data and materials

Data availability is not applicable to this review as the data used were synthesised from previous studies.

Abbreviations

Confidence intervals

• Hepatitis B virus

National Institute on Minority Health and Health Disparity

Odds ratios

Participant-Intervention-Comparator-Outcomes-Study design

Preferred Reporting Items for Systematic Reviews and Meta-analyses

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Acknowledgements

The authors would like to acknowledge the medical librarian Dr. Kendy from the Chinese University of Hong Kong for her assistance in refining the search strategy of this mixed-method systematic review.

This review was funded by the Scientific Research Start-up Fee of the Eighth Affiliated Hospital, Sun Yat-sen University, China (GCCRCYJ072).

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CL and XF designed the study. CL, DT, QM, and YG performed the two-round study screening process. CL and YG extracted data from the included studies. CL and QM performed the study quality appraisal. CL analysed the data and wrote the manuscript. All authors read, revised, and approved the final manuscript.

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Correspondence to Xia Fu .

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Li, C., Thapa, D., Mi, Q. et al. Disparities in hepatitis B virus healthcare service access among marginalised poor populations: a mixed-method systematic review. Infect Dis Poverty 13 , 58 (2024). https://doi.org/10.1186/s40249-024-01225-0

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Received : 20 April 2024

Accepted : 08 July 2024

Published : 09 August 2024

DOI : https://doi.org/10.1186/s40249-024-01225-0

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ORIGINAL RESEARCH article

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis b.

• First Affiliated Hospital of Anhui Medical University, Hefei, China

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Background: The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Objective: Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Methods: Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n=732) and an internal validation cohort (n=242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC) , and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n=771), respectively. Results: Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC=0.834, 95% CI 0.800-0.868, p<0.05) and internal validation cohort (AUC=0.804, 95% CI 0.742-0.866, p<0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. Conclusions: This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients

Keywords: Chronic hepatitis B, liver fibrosis, nomogram, Machine learning model, Lasso regression analysis

Received: 21 Jun 2024; Accepted: 13 Aug 2024.

Copyright: © 2024 Han, Wang, Song, Kang, Lin, Hu, Sun and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yufeng Gao, First Affiliated Hospital of Anhui Medical University, Hefei, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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