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Article ; Online: Challenges for hepatitis B virus cure in resource-limited settings in sub-Saharan Africa.

Kramvis, Anna

2020 Volume 15, Issue 3, Page(s) 185–192

Abstract: Purpose of review: The aim of this article is to highlight the unique challenges for hepatitis B virus (HBV) cure faced in resource-limited settings (RLS) in sub-Saharan Africa (SSA), where access to disease prevention measures, medical testing, and ... ...

Abstract	Purpose of review: The aim of this article is to highlight the unique challenges for hepatitis B virus (HBV) cure faced in resource-limited settings (RLS) in sub-Saharan Africa (SSA), where access to disease prevention measures, medical testing, and treatment are limited. Recent findings: SSA RLS face challenges, which need to be anticipated as HBV cure research advances. There is a paucity of data because of lack of HBV surveillance and limited access to laboratories. Interruption of transfusion-transmitted infections, perinatal mother-to-child-transmissions, and transmission in people-who-infect-drug networks has not been achieved fully. Although RLS in SSA are within the epicenter of the HIV pandemic, unlike for HIV, there is no population-based testing for HBV. Public health response to HBV is inadequate with concomitant political inertia in combatting HBV infection. Summary: A functional HBV cure will improve the diagnosis/treatment cascade, decrease costs and accelerate HBV elimination. There is a concerted effort to find a HBV cure, which will be finite, not require life-long treatment, adherence, and continued monitoring. Increased research, improved financial, infrastructural and human resources will positively impact on implementation of HBV cure, when available. We can emulate major strides made in tackling HIV and the strength of advocacy groups in soliciting policymakers to take action.
MeSH term(s)	Africa South of the Sahara ; Female ; HIV Infections ; Hepatitis B/transmission ; Hepatitis B virus ; Humans ; Infectious Disease Transmission, Vertical ; Pregnancy
Language	English
Publishing date	2020-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0000000000000619
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Article ; Online: Navigating TREAT-B in resource-limited settings.

Kramvis, Anna / Lau, Daryl T Y

The Lancet. Global health

2023 Volume 12, Issue 1, Page(s) e8–e9

MeSH term(s)	Humans ; Resource-Limited Settings ; Developing Countries
Language	English
Publishing date	2023-12-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(23)00551-X
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Article ; Online: Imaging Techniques: Essential Tools for the Study of SARS-CoV-2 Infection.

Deroubaix, Aurélie / Kramvis, Anna

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 794264

Abstract: The world has seen the emergence of a new virus in 2019, SARS-CoV-2, causing the COVID-19 pandemic and millions of deaths worldwide. Microscopy can be much more informative than conventional detection methods such as RT-PCR. This review aims to present ... ...

Abstract	The world has seen the emergence of a new virus in 2019, SARS-CoV-2, causing the COVID-19 pandemic and millions of deaths worldwide. Microscopy can be much more informative than conventional detection methods such as RT-PCR. This review aims to present the up-to-date microscopy observations in patients, the
MeSH term(s)	COVID-19 ; COVID-19 Testing ; Humans ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.794264
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Article ; Online: The Complex Role of HBeAg and Its Precursors in the Pathway to Hepatocellular Carcinoma.

Padarath, Kiyasha / Deroubaix, Aurélie / Kramvis, Anna

Viruses

2023 Volume 15, Issue 4

Abstract: Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is ... ...

Abstract	Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been implicated in promoting this persistence. The precursor of hepatitis e antigen (HBeAg), is translated from the precore/core region and is post-translationally modified to yield HBeAg, which is secreted in the serum. HBeAg is a non-particulate protein of HBV and can act as both a tolerogen and an immunogen. HBeAg can protect hepatocytes from apoptosis by interfering with host signalling pathways and acting as a decoy to the immune response. By evading the immune response and interfering with apoptosis, HBeAg has the potential to contribute to the hepatocarcinogenic potential of HBV. In particular, this review summarises the various signalling pathways through which HBeAg and its precursors can promote hepatocarcinogenesis via the various hallmarks of cancer.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular ; Hepatitis B e Antigens/metabolism ; Liver Neoplasms ; Hepatitis B virus/genetics ; Hepatitis B ; Hepatitis B, Chronic ; Mutation ; DNA, Viral/metabolism
Chemical Substances	Hepatitis B e Antigens ; DNA, Viral
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15040857
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Article ; Online: Exploring the optimal vaccination strategy against hepatitis B virus in childhood (Review).

Kramvis, Anna / Mammas, Ioannis N / Spandidos, Demetrios A

Biomedical reports

2023 Volume 19, Issue 1, Page(s) 48

Abstract: Vaccination against hepatitis B virus (HBV) remains the most effective strategy against HBV infection in humans. The present review summarized the optimal vaccination strategies against HBV in childhood. The following points are discussed: i) When and ... ...

Abstract	Vaccination against hepatitis B virus (HBV) remains the most effective strategy against HBV infection in humans. The present review summarized the optimal vaccination strategies against HBV in childhood. The following points are discussed: i) When and how the first HBV vaccines were developed; ii) the dosages, schedules and injection routes that are used for HBV vaccination; iii) the contraindications for HBV vaccination in the general paediatric population; iv) the challenges with the use of multivalent vaccines; v) the long-term immunogenicity and duration of protection against HBV; vi) the use of selective HBV vaccination and the hepatitis B immune globulin strategy in HBV-exposed infants; and vii) the effectiveness of the current HBV vaccination schemes. The present review is based on a Paediatric Virology Study Group (PVSG) webinar performed in the context of the 8th Workshop on Paediatric Virology.
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2763624-0
ISSN	2049-9442 ; 2049-9434
ISSN (online)	2049-9442
ISSN	2049-9434
DOI	10.3892/br.2023.1631
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Article ; Online: In vitro expression of precore proteins of hepatitis B virus subgenotype A1 is affected by HBcAg, and can affect HBsAg secretion.

Deroubaix, Aurélie / Kramvis, Anna

Scientific reports

2021 Volume 11, Issue 1, Page(s) 8167

Abstract: HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique ... ...

Abstract	HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique molecular characteristics in the basic core promoter/precore regions. Carriers of A1 exhibit early HBeAg loss. We sought to further characterize the precore proteins of A1 in vitro. HuH-7 cells were transfected with subgenomic constructs expressing individual precore proteins. Western blot analysis using DAKO anti-core antibody showed the expected sizes and a 1 kDa larger band for P22, P20 and P17. Using confocal microscopy, a cytoplasmic accumulation of HBeAg and precursors was observed with P25-expressing plasmid, whereas P22 localized both in the cytoplasm and nucleus. P20 and P17, which lack the carboxy end of P22 showed strong nuclear accumulation, implicating a nuclear localization signal in the N-terminal 10 amino acids. G1862T, unique to subgenotype A1, is frequently found in HBV from HCC patients. P25 with G1862T showed delayed and reduced HBeAg expression/secretion. Knock-out of core in the replication competent clones led to precore protein accumulation in the cytoplasm/perinuclear region, and decreased HBeAg secretion. Knock-out of precore proteins increased HBsAg secretion but intracellular HBsAg expression was unaffected. Over-expression of precore proteins in trans led to decreased HBsAg expression and secretion. Intracellular trafficking of HBV A1 precore proteins was followed. This was unaffected by the CMV promoter and different cell types. In the viral context, precore protein expression was affected by absence of core, and affected HBsAg expression, suggesting an interrelationship between precore proteins, HBcAg and HBsAg. This modulatory role of HBeAg and its precursors may be important in viral persistence and ultimate development of HCC.
MeSH term(s)	Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/virology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Genotype ; Hep G2 Cells ; Hepatitis B Core Antigens/genetics ; Hepatitis B Core Antigens/metabolism ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Surface Antigens/metabolism ; Hepatitis B e Antigens ; Hepatitis B virus/genetics ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/virology ; Promoter Regions, Genetic ; Protein Transport
Chemical Substances	Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens
Language	English
Publishing date	2021-04-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-87529-9
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Article ; Online: The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics.

Kramvis, Anna

Reviews in medical virology

2016 Volume 26, Issue 4, Page(s) 285–303

Abstract: Although a successful vaccine against HBV has been implemented in 184 countries, eradication of hepatitis B virus (HBV) is still not on the horizon. There are over 240 million chronic carriers of HBV globally. The risk of developing chronic hepatitis ... ...

Abstract	Although a successful vaccine against HBV has been implemented in 184 countries, eradication of hepatitis B virus (HBV) is still not on the horizon. There are over 240 million chronic carriers of HBV globally. The risk of developing chronic hepatitis ranges from >90% in newborns of hepatitis Be antigen (HBeAg)-positive mothers, 25%-35% in children under 5 years of age and <5% in adults. HBeAg, a non-particulate viral protein, is a marker of HBV replication. This is the only HBV antigen to cross the placenta, leading to specific unresponsiveness of helper T cells to the capsid protein and HBeAg in newborns. HBeAg is tolerated in utero and acts as a tolerogen after birth. Perinatal transmission is frequent when mothers are HBeAg-positive, whereas it occurs less frequently when mothers are HBeAg-negative. Sequence heterogeneity is a feature of HBV. Based on an intergroup divergence >7.5% across the complete genome, HBV is classified phylogenetically into at least nine genotypes. With between ~4% and 8% intergroup nucleotide divergence, genotypes A-D, F, H and I are classified further into subgenotypes. HBV genotypes/subgenotypes may have distinct geographical distribution and can develop different mutations in the regions of the HBV genome that code for HBeAg. These differences can be related to the role of HBV genotypes to the natural history of infection and mode of transmission. Thus genotypes/subgenotypes of HBV can be responsible for the different natural history of infection and modes of transmission in children, found in various regions of the world, where different genotypes/subgenotypes prevail. Copyright © 2016 John Wiley & Sons, Ltd.
MeSH term(s)	DNA, Viral/genetics ; Genetic Variation ; Genotype ; Hepatitis B/pathology ; Hepatitis B/virology ; Hepatitis B e Antigens/blood ; Hepatitis B virus/classification ; Hepatitis B virus/genetics ; Hepatitis B virus/pathogenicity ; Humans ; Phylogeography
Chemical Substances	DNA, Viral ; Hepatitis B e Antigens
Language	English
Publishing date	2016-05-03
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1086043-5
ISSN	1099-1654 ; 1052-9276
ISSN (online)	1099-1654
ISSN	1052-9276
DOI	10.1002/rmv.1885
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Article ; Online: Hepatitis B virus immunity prior to and after administration of a 'booster' dose of vaccine among health-care students at a South African university.

Makan, Nisha / Song, Ernest / Kinge, Constance Wose / Kramvis, Anna

Vaccine: X

2023 Volume 14, Page(s) 100284

Abstract: Background: Health-care students (HCSs) are at risk of occupational exposure to hepatitis B virus (HBV) infection despite an effective hepatitis B vaccine (HepB) being available. The majority of current HCSs are born after HepB was introduced into the ... ...

Abstract	Background: Health-care students (HCSs) are at risk of occupational exposure to hepatitis B virus (HBV) infection despite an effective hepatitis B vaccine (HepB) being available. The majority of current HCSs are born after HepB was introduced into the South African Expanded Programme on Immunisation in 1995. Thus, it is assumed that having received HepB in infancy, a single 'booster' dose would suffice. This study aimed to investigate HBV immunity prior to and after administration of a HepB 'booster' dose. Methods: Hepatitis B surface antibody (anti-HBs) levels were determined in first year HCSs at the University of the Witwatersrand, before and after receiving the 'booster'. Participant demographics and HepB history were captured using a structured questionnaire. Results: Before receiving the 'booster', 56% (101/180) had anti-HBs < 10 mIU/mL and were non-immune. A further 35% had anti-HBs levels of 10 - 99 mIU/mL, and 9% had ≥100 mIU/mL. <30% of HCSs self-reported completion of a three-dose primary series, which was significantly associated with higher baseline anti-HBs levels compared to those with a partial schedule ( Conclusion: More than half of the HCSs were not immune to HBV prior to receiving the recommended 'booster' vaccine. Following vaccination, 7% (5/71) remained unprotected. This study highlights that in the absence of vaccination records and without confirming the immune status of HCSs, it cannot be assumed that HCSs will be protected following a 'booster'. Policy reform and inclusion of serological tests for immunity prior to HCSs initiating clinical exposure are recommended.
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article
ISSN	2590-1362
ISSN (online)	2590-1362
DOI	10.1016/j.jvacx.2023.100284
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Article: Genotype E: The neglected genotype of hepatitis B virus.

Ingasia, Luicer Anne Olubayo / Wose Kinge, Constance / Kramvis, Anna

World journal of hepatology

2022 Volume 13, Issue 12, Page(s) 1875–1891

Abstract: Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the ... ...

Abstract	Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573703-X
ISSN	1948-5182
ISSN	1948-5182
DOI	10.4254/wjh.v13.i12.1875
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Article ; Online: Molecular characterization of hepatitis B virus isolated from Black South African cancer patients, with and without hepatocellular carcinoma.

Mak, Daniel / Kramvis, Anna

Archives of virology

2020 Volume 165, Issue 8, Page(s) 1815–1825

Abstract: In South Africa (SA), hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma (HCC). As HBV genotypes/subgenotypes and mutations can influence disease manifestation and progression, our aim was to molecularly characterize ... ...

Abstract	In South Africa (SA), hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma (HCC). As HBV genotypes/subgenotypes and mutations can influence disease manifestation and progression, our aim was to molecularly characterize HBV in Black cancer patients, with and without HCC. The basal core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolates were amplified and sequenced from 55 HCC cases and 22 non-HCC cancer controls. Phylogenetic analysis of 43 polymerase/complete S region amplicons showed that the majority (88.4%) clustered with subgenotype A1, 4.7% with A2, and 7% with A3. The following mutations were significantly more frequent in HCC cases than in controls (p < 0.05): in the BCP/PC 1753C/G (22.5% vs. 0%), 1764A (69.4% vs. 38.1%), and T64C (51.5% vs. 20%) in the preS2, which results in a F22L substitution. PreS1 and preS2 start codon mutants were detected only in HCC cases, occurring in two and 16 isolates, respectively. PreS deletion mutants were isolated from 11 HCC cases, which had a HBV viral load > 10,000 IU/mL and were significantly younger than non-HCC controls (34 ± 7.1 vs. 41.2 ± 9.5 years, p = 0.05). The 1762T/1764A double mutation was detected in the majority (90.9%) of the isolates from HCC cases with preS deletions. Black HBV carriers were mainly infected with subgenotype A1, with HCC cases carrying BCP/PC and preS mutant strains that are associated with hepatocarcinogenesis. This is the first study to compare the molecular characteristics of HBV from HCC and non-HCC cancer patients in SA.
MeSH term(s)	Adult ; Carcinoma, Hepatocellular/virology ; Case-Control Studies ; DNA, Viral/genetics ; Female ; Genotype ; Hepatitis B/virology ; Hepatitis B Surface Antigens/genetics ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/virology ; Humans ; Liver Neoplasms/virology ; Male ; Middle Aged ; Mutation/genetics ; Phylogeny ; Promoter Regions, Genetic/genetics ; Retrospective Studies ; South Africa ; Viral Load/genetics
Chemical Substances	DNA, Viral ; Hepatitis B Surface Antigens
Language	English
Publishing date	2020-06-05
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-020-04686-4
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