Evidence map›Paper›PMID 29859062›Full record

ArticleBMC infectious diseases2018

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.

Luna Colagrossi, Lucas E Hermans, Romina Salpini, Domenico Di Carlo, Suzan D Pas, Marta Alvarez, Ziv Ben-Ari, Greet Boland, Bianca Bruzzone, Nicola Coppola and 30 more

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in BMC infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 53 citations in OpenAlex.

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  14. Hepatitis B eradication: vaccine as a key player.American journal of translational research · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 20 institutions in 17 countries.

Luna ColagrossiDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.
Lucas E HermansVirology, Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Romina SalpiniDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.
Domenico Di CarloDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.
Suzan D PasDepartment of Viroscience, Erasmus Medical Centre, Rotterdam, The Netherlands.
Marta AlvarezServicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada, Granada, Spain.
Ziv Ben-AriLiver Disease Centre, Sheba Medical Centre, Ramat Gan, Israel.
Greet BolandVirology, Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Bianca BruzzoneHygiene Unit, IRCCS AOU San Martino - IST, Genoa, Italy.
Nicola CoppolaMalattie Infettive, Seconda Università degli studi di Napoli, Naples, Italy.
Carole Seguin-DevauxLaboratory of Retrovirology, CRP-Santé, Luxembourg, Luxembourg.
Tomasz DydaMolecular Diagnostics Laboratory, Hospital of Infectious Diseases, Warsaw, Poland.
Federico GarciaServicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada, Granada, Spain.
Rolf KaiserInstitute of Virology, University of Cologne, Cologne, Germany.
Sukran KöseIzmir Tepecik Education and Research Hospital, Clinic of Infectious Diseases and Clinical Microbiology, Izmir, Turkey.
Henrik KrarupSection of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
Ivana LazarevicInstitute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Maja M LunarInstitute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Sarah MaylinService de Microbiologie, University Paris Diderot, Hôpital Saint Louis, Paris, France.
Valeria MicheliL. Sacco Hospital, Milan, Italy.
Orna MorNational HIV Reference Laboratory, Central Virology Laboratory, Ministry of Health, Tel Hashomer, Ramat Gan, Israel.
Simona ParaschivMolecular Diagnostics Laboratory, National Institute for Infectious Diseases "Matei Bals", Bucharest, Romania.
Dimitros ParaskevisNational Retrovirus Reference Centre, Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Mario PoljakInstitute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Elisabeth Puchhammer-StöcklDepartment for Virology, Medical University of Vienna, Vienna, Austria.
François SimonService de Microbiologie, University Paris Diderot, Hôpital Saint Louis, Paris, France.
Maja StanojevicInstitute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Kathrine Stene-JohansenDepartment of Virology, Norwegian Institute of Public Health, Oslo, Norway.
Nijaz TihicInstitute of Microbiology, Polyclinic for Laboratory Diagnostics, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina.
Pascale TrimouletVirology Laboratory, Centre Hospitalier Régional et Université "Victor Segalen", Bordeaux, France.
Jens VerheyenInstitute of Virology, University-Hospital, University Duisburg-Essen, Essen, Germany.
Adriana VinceUniversity of Zagreb School of Medicine and University Hospital for Infectious Diseases, Zagreb, Croatia.
Snjezana Zidovec LepejUniversity of Zagreb School of Medicine and University Hospital for Infectious Diseases, Zagreb, Croatia.
Nina WeisDepartment of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Tülay YalcinkayaRefik Saydam National Public Health Agency, Ankara, Turkey.
Charles A B BoucherDepartment of Viroscience, Erasmus Medical Centre, Rotterdam, The Netherlands.
Annemarie M J WensingVirology, Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Carlo F PernoDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy. cf.perno@uniroma2.it.
Valentina SvicherDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy. valentina.svicher@uniroma2.it.ORCID 0000-0002-2377-504X
HEPVIR working group of the European Society for translational antiviral research (ESAR)
University of Rome Tor Vergata · ITUniversity Medical Center Utrecht · NLDélégation Paris 7 · FRErasmus University Rotterdam · NLInstituto de Investigación Biosanitaria de Granada · ESUniversity of Belgrade · RSUniversity of Ljubljana · SIUniversity of Zagreb · HRAalborg University Hospital · DKCopenhagen University Hospital · DKIsrael Ministry of Health · ILIzmir Tepecik Eğitim ve Araştırma Hastanesi · TRLaboratoire National de Santé · LULuigi Sacco Hospital · ITMedical University of Vienna · ATNational and Kapodistrian University of Athens · GRNational Institute of Research and Development for Biological Sciences · RONorwegian Institute of Public Health · NOOspedale Policlinico San Martino · ITSheba Medical Center · IL

Funding

FIRB project RBAP11YS7K_001InterOmics PB05
6 · The paper itself

Abstract

backgroundHBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe.

methodsThis study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence.

resultsAt least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties.

conclusionsImmune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.

Indexed as

Codon, TerminatorMutationAdultAmino Acid SubstitutionAntiviral AgentsEuropeFemaleGenotypeHepatitis B, ChronicHepatitis B Surface AntigensHepatitis B virusHumansMaleMiddle AgedAntiviral AgentsCodon, TerminatorHepatitis B Surface AntigensDrug-resistanceHBsAgHBVImmune-escapeStop-codons

Identifiers

PMID29859062
PMCPMC5984771
OpenAlexW2805190163

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.