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Article ; Online: Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?

Pley, Caitlin / Lourenço, José / McNaughton, Anna L / Matthews, Philippa C

2022 Volume 96, Issue 9, Page(s) e0005122

Abstract: Hepatitis B virus (HBV) polymerase is divided into terminal protein, spacer, reverse transcriptase, and RNase domains. Spacer has previously been considered dispensable, merely acting as a tether between other domains or providing plasticity to ... ...

Abstract	Hepatitis B virus (HBV) polymerase is divided into terminal protein, spacer, reverse transcriptase, and RNase domains. Spacer has previously been considered dispensable, merely acting as a tether between other domains or providing plasticity to accommodate deletions and mutations. We explore evidence for the role of spacer sequence, structure, and function in HBV evolution and lineage, consider its associations with escape from drugs, vaccines, and immune responses, and review its potential impacts on disease outcomes.
MeSH term(s)	Gene Products, pol ; Genotype ; Hepatitis B virus/genetics ; Mutation ; Protein Domains ; RNA-Directed DNA Polymerase/genetics ; Viral Proteins/genetics
Chemical Substances	Gene Products, pol ; P protein, Hepatitis B virus ; Viral Proteins ; RNA-Directed DNA Polymerase (EC 2.7.7.49)
Language	English
Publishing date	2022-04-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00051-22
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Article: Polymorphisms predicting phylogeny in hepatitis B virus.

Lourenço, José / McNaughton, Anna L / Pley, Caitlin / Obolski, Uri / Gupta, Sunetra / Matthews, Philippa C

Virus evolution

2022 Volume 9, Issue 1, Page(s) veac116

Abstract: Hepatitis B viruses (HBVs) are compact viruses with circular genomes of ∼3.2 kb in length. Four genes ( ...

Abstract	Hepatitis B viruses (HBVs) are compact viruses with circular genomes of ∼3.2 kb in length. Four genes (
Language	English
Publishing date	2022-12-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2818949-8
ISSN	2057-1577
ISSN	2057-1577
DOI	10.1093/ve/veac116
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Article: The global impact of the COVID-19 pandemic on the prevention, diagnosis and treatment of hepatitis B virus (HBV) infection.

Pley, Caitlin M / McNaughton, Anna L / Matthews, Philippa C / Lourenço, José

BMJ global health

2021 Volume 6, Issue 1

Abstract: The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is ... ...

Abstract	The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is accruing on the broader consequences of such interventions on economic and public health inequalities, as well as on pre-existing programmes targeting endemic pathogens. We provide an overview of the impact of the ongoing COVID-19 pandemic on hepatitis B virus (HBV) programmes globally, focusing on the possible consequences for prevention, diagnosis and treatment. Ongoing disruptions to infrastructure, supply chains, services and interventions for HBV are likely to contribute disproportionately to the short-term incidence of chronic hepatitis B, providing a long-term source of onward transmission to future generations that threatens progress towards the 2030 elimination goals.
MeSH term(s)	COVID-19 ; Health Services Accessibility ; Healthcare Disparities ; Hepatitis B/diagnosis ; Hepatitis B/prevention & control ; Hepatitis B/therapy ; Hepatitis B/transmission ; Humans ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2059-7908
ISSN	2059-7908
DOI	10.1136/bmjgh-2020-004275
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Article: Hepatitis B Virus Prevalence and Mother-to-Child Transmission Risk in an HIV Early Intervention Cohort in KwaZulu-Natal, South Africa.

Millar, Jane / Cromhout, Gabriela Z L / Mchunu, Noxolo / Bengu, Nomonde / Ndung'u, Thumbi / Goulder, Philip J / Matthews, Philippa C / McNaughton, Anna L

Open forum infectious diseases

2023 Volume 10, Issue 8, Page(s) ofad366

Abstract: Background: HIV and hepatitis B virus (HBV) prevalence are both high in KwaZulu-Natal, South Africa. HIV coinfection negatively affects HBV prognosis and can increase the likelihood of HBV mother-to-child transmission (MTCT). In an early HIV infant ... ...

Abstract	Background: HIV and hepatitis B virus (HBV) prevalence are both high in KwaZulu-Natal, South Africa. HIV coinfection negatively affects HBV prognosis and can increase the likelihood of HBV mother-to-child transmission (MTCT). In an early HIV infant treatment intervention cohort of HIV-transmitting mother-child pairs in KwaZulu-Natal, we characterized maternal HBV prevalence and screened infants at risk. Methods: Infants were treated for HIV MTCT at birth, and combination regimens incidentally active against HBV were initiated within 21 days. Maternal samples (N = 175) were screened at birth for HBV infection (HBV surface antigen [HBsAg]), exposure to HBV (HBV anti-core IgG), and vaccination responses (HBV anti-S positive without other HBV markers). Infants of mothers who were HBV positive were screened for HBsAg at 1 and 12 months. Results: Evidence of HBV infection was present in 8.6% (n = 15) of maternal samples. Biomarkers for HBV exposure were present in 31.4% (n = 55). Evidence of HBV vaccination was uncommon in mothers (8.0%; n = 14). Despite prescription of antiretroviral therapy (ART) active against HBV, HBV DNA was detectable in 46.7% (7/15) of mothers who were HBsAg positive. Three mothers had HBV viral loads >5.3 log Discussion: This vulnerable cohort of HIV-transmitting mothers had a high prevalence of undiagnosed HBV. Early infant ART may have reduced the risk of MTCT in high-risk cases. Current HBV guidelines recommend ART prophylaxis, but these data underline the pressing need to increase availability of birth dose vaccines.
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad366
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Article ; Online: Extending treatment eligibility for chronic hepatitis B virus infection.

McNaughton, Anna L / Lemoine, Maud / van Rensburg, Christo / Matthews, Philippa C

Nature reviews. Gastroenterology & hepatology

2020 Volume 18, Issue 3, Page(s) 146–147

MeSH term(s)	Antiviral Agents/therapeutic use ; Eligibility Determination ; Hepatitis B Vaccines ; Hepatitis B, Chronic/epidemiology ; Hepatitis B, Chronic/prevention & control ; Hepatitis B, Chronic/transmission ; Humans
Chemical Substances	Antiviral Agents ; Hepatitis B Vaccines
Language	English
Publishing date	2020-12-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-020-00398-x
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Article ; Online: Estimating hepatitis B virus prevalence among key population groups for European Union and European Economic Area countries and the United Kingdom: a modelling study.

Trickey, Adam / Bivegete, Sandra / Duffell, Erika / McNaughton, Anna L / Nerlander, Lina / Walker, Josephine G / Fraser, Hannah / Hickman, Matthew / Vickerman, Peter / Brooks-Pollock, Ellen / Christensen, Hannah

BMC infectious diseases

2023 Volume 23, Issue 1, Page(s) 457

Abstract: Background: Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for ...

Abstract	Background: Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for each country in the European Union, European Economic Area and the United Kingdom (EU/EEA/UK), including where data are currently unavailable. Methods: We combined data from a 2018 systematic review (updated in 2021), data gathered directly by the European Centre for Disease Control (ECDC) from EU/EEA countries and the UK and further country-level data. We included data on adults from the general population, pregnant women, first time blood donors (FTBD), men who have sex with men (MSM), prisoners, people who inject drugs (PWID), and migrants from 2001 to 2021, with three exceptions made for pre-2001 estimates. Finite Mixture Models (FMM) and Beta regression were used to predict country and population group HBsAg prevalence. A separate multiplier method was used to estimate HBsAg prevalence among the migrant populations within each country, due to biases in the data available. Results: There were 595 included studies from 31 countries (N = 41,955,969 people): 66 were among the general population (mean prevalence ([Formula: see text]) 1.3% [range: 0.0-7.6%]), 52 among pregnant women ([Formula: see text]1.1% [0.1-5.3%]), 315 among FTBD ([Formula: see text]0.3% [0.0-6.2%]), 20 among MSM ([Formula: see text]1.7% [0.0-11.2%]), 34 among PWID ([Formula: see text]3.9% [0.0-16.9%]), 24 among prisoners ([Formula: see text]2.9% [0.0-10.7%]), and 84 among migrants ([Formula: see text]7.0% [0.2-37.3%]). The FMM grouped countries into 3 classes. We estimated HBsAg prevalence among the general population to be < 1% in 24/31 countries, although it was higher in 7 Eastern/Southern European countries. HBsAg prevalence among each population group was higher in most Eastern/Southern European than Western/Northern European countries, whilst prevalence among PWID and prisoners was estimated at > 1% for most countries. Portugal had the highest estimated prevalence of HBsAg among migrants (5.0%), with the other highest prevalences mostly seen in Southern Europe. Conclusions: We estimated HBV prevalence for each population group within each EU/EAA country and the UK, with general population HBV prevalence to be < 1% in most countries. Further evidence is required on the HBsAg prevalence of high-risk populations for future evidence synthesis.
MeSH term(s)	Pregnancy ; Adult ; Male ; Humans ; Female ; European Union ; Hepatitis B virus ; Population Groups ; Homosexuality, Male ; Prevalence ; Hepatitis B Surface Antigens ; Substance Abuse, Intravenous ; Sexual and Gender Minorities ; United Kingdom/epidemiology ; Europe/epidemiology
Chemical Substances	Hepatitis B Surface Antigens
Language	English
Publishing date	2023-07-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-023-08433-3
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Article ; Online: The global impact of the COVID-19 pandemic on the prevention, diagnosis and treatment of hepatitis B virus (HBV) infection

Anna L McNaughton / Philippa C Matthews / Caitlin M Pley / José Lourenço

BMJ Global Health, Vol 6, Iss

2021 Volume 1

Abstract	The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is accruing on the broader consequences of such interventions on economic and public health inequalities, as well as on pre-existing programmes targeting endemic pathogens. We provide an overview of the impact of the ongoing COVID-19 pandemic on hepatitis B virus (HBV) programmes globally, focusing on the possible consequences for prevention, diagnosis and treatment. Ongoing disruptions to infrastructure, supply chains, services and interventions for HBV are likely to contribute disproportionately to the short-term incidence of chronic hepatitis B, providing a long-term source of onward transmission to future generations that threatens progress towards the 2030 elimination goals.
Keywords	Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
Subject code	306
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
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Article ; Online: Trends in HIV incidence following scale-up of harm reduction interventions among people who inject drugs in Kachin, Myanmar, 2008-2020: analysis of a retrospective cohort dataset.

McNaughton, Anna L / Stone, Jack / Oo, Khine Thet / Let, Zaw Zen / Taw, Mar / Aung, Minn Thit / Min, Aung Myo / Lim, Aaron G / Wisse, Ernst / Vickerman, Peter

The Lancet regional health. Western Pacific

2023 Volume 34, Page(s) 100718

Abstract: Background: People who inject drugs (PWID) in Kachin, Myanmar, have a high HIV prevalence (>40%), but there is no data on incidence. We used HIV testing data from three harm reduction drop-in centres (DIC) in Kachin (2008-2020) to determine HIV ... ...

Abstract	Background: People who inject drugs (PWID) in Kachin, Myanmar, have a high HIV prevalence (>40%), but there is no data on incidence. We used HIV testing data from three harm reduction drop-in centres (DIC) in Kachin (2008-2020) to determine HIV incidence trends among PWID and associations with intervention uptake. Methods: Individuals were HIV-tested at first DIC visit and periodically thereafter, during which demographic and risk behaviour data were collected. Two DIC provided opioid agonist therapy (OAT) from 2008. Monthly DIC-level needle/syringe provision (NSP) data was available from 2012. Site-level 6-monthly NSP coverage was denoted low, high, or medium if it was below the lower quartile, above upper quartile, between these quartiles of provision levels over 2012-2020, respectively. HIV incidence was estimated by linking subsequent test records for those initially testing HIV-negative. Associations with HIV incidence were examined using Cox regression. Findings: Follow-up HIV testing data was available for 31.4% (2227) of PWID initially testing HIV-negative, with 444 incident HIV infections during 6266.5 person years (py) of follow-up. Overall HIV incidence was 7.1 per 100 py (95% confidence interval 6.5-7.8), which decreased from 19.3 (13.3-28.2) in 2008-11 to 5.2 per 100 py (4.6-5.9) in 2017-20. In the full PWID incidence dataset after adjustment for various factors, recent (≤6 weeks) injecting (aHR 1.74, 1.35-2.25) and needle sharing (aHR 2.00, 1.48-2.70) were associated with higher incidence, while longer injection careers were associated with reduced incidence (aHR 0.54, 0.34-0.86, for 2-5 yrs vs <2 yrs). In a reduced dataset including data on OAT access and NSP coverage (2012-2020 for two DIC providing OAT), being on OAT during follow-up was associated with reduced HIV incidence (aHR 0.36, 0.27-0.48, compared to never being on OAT) as was high NSP coverage (aHR 0.64, 0.48-0.84, compared to medium syringe coverage). Interpretation: Although HIV incidence is high among PWID in Kachin, data suggests it has decreased since the scale-up in harm reduction interventions. Funding: US NIH, Médecins du Monde.
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article
ISSN	2666-6065
ISSN (online)	2666-6065
DOI	10.1016/j.lanwpc.2023.100718
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Article ; Online: Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences.

McNaughton, Anna L / Revill, Peter A / Littlejohn, Margaret / Matthews, Philippa C / Ansari, M Azim

The Journal of general virology

2020 Volume 101, Issue 3, Page(s) 271–283

Abstract: Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), characterized thus far. Given the broadening interest in HBV sequencing, there is an increasing requirement for a ... ...

Abstract	Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), characterized thus far. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level. All of the generated data, including the alignments, phylogenies and chosen reference sequences, are available online (https://doi.org/10.6084/m9.figshare.8851946) as a simple open-access resource.
MeSH term(s)	Base Sequence/genetics ; DNA, Viral/genetics ; Databases, Genetic ; Genome, Viral ; Genotype ; Hepatitis B/virology ; Hepatitis B virus/genetics ; Humans ; Phylogeny ; Sequence Analysis, DNA
Chemical Substances	DNA, Viral
Language	English
Publishing date	2020-03-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001387
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Article ; Online: Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta-analysis.

Campbell, Cori / Wang, Tingyan / McNaughton, Anna L / Barnes, Eleanor / Matthews, Philippa C

Journal of viral hepatitis

2020 Volume 28, Issue 3, Page(s) 493–507

Abstract: Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and ...

Abstract	Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta-analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta-analysis and generated pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta-analysis. DM was associated with >25% increase in hazards of HCC (fixed-effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20-1.32, random-effects HR 1.36, 95% CI 1.23-1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
MeSH term(s)	Adult ; Carcinoma, Hepatocellular/epidemiology ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/epidemiology ; Humans ; Liver Neoplasms/epidemiology ; Risk Factors
Language	English
Publishing date	2020-12-28
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13452
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