Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.
Identifieur interne : 001E94 ( PubMed/Corpus ); précédent : 001E93; suivant : 001E95Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.
Auteurs : A. Velay ; H. Jeulin ; M. Eschlimann ; B. Malvé ; F. Goehringer ; M. Bensenane ; J-P Frippiat ; P. Abraham ; A M Ismail ; J M Murray ; C. Combet ; F. Zoulim ; J-P Bronowicki ; E. SchvoererSource :
- Journal of viral hepatitis [ 1365-2893 ] ; 2016.
English descriptors
- KwdEn :
- Adult, Aged, Amino Acid Substitution, Animals, Antigenic Variation, Antiviral Agents (therapeutic use), Computational Biology, Enzyme-Linked Immunosorbent Assay, Female, Genetic Variation, Hepatitis B Surface Antigens (genetics), Hepatitis B Surface Antigens (immunology), Hepatitis B, Chronic (drug therapy), Humans, Male, Mice, Inbred BALB C, Middle Aged, Mutant Proteins (genetics), Mutant Proteins (immunology), Nucleosides (therapeutic use), Nucleotides (therapeutic use), Sequence Analysis, DNA.
- MESH :
- chemical , genetics : Hepatitis B Surface Antigens, Mutant Proteins.
- chemical , immunology : Hepatitis B Surface Antigens, Mutant Proteins.
- chemical , therapeutic use : Antiviral Agents, Nucleosides, Nucleotides.
- drug therapy : Hepatitis B, Chronic.
- Adult, Aged, Amino Acid Substitution, Animals, Antigenic Variation, Computational Biology, Enzyme-Linked Immunosorbent Assay, Female, Genetic Variation, Humans, Male, Mice, Inbred BALB C, Middle Aged, Sequence Analysis, DNA.
Abstract
For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.
DOI: 10.1111/jvh.12498
PubMed: 26742490
Links to Exploration step
pubmed:26742490Le document en format XML
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Eschlimann</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Malve, B" sort="Malve, B" uniqKey="Malve B" first="B" last="Malvé">B. Malvé</name><affiliation><nlm:affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Goehringer, F" sort="Goehringer, F" uniqKey="Goehringer F" first="F" last="Goehringer">F. Goehringer</name><affiliation><nlm:affiliation>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bensenane, M" sort="Bensenane, M" uniqKey="Bensenane M" first="M" last="Bensenane">M. 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Abraham</name><affiliation><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation></affiliation></author><author><name sortKey="Ismail, A M" sort="Ismail, A M" uniqKey="Ismail A" first="A M" last="Ismail">A M Ismail</name><affiliation><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation></affiliation></author><author><name sortKey="Murray, J M" sort="Murray, J M" uniqKey="Murray J" first="J M" last="Murray">J M Murray</name><affiliation><nlm:affiliation>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Combet, C" sort="Combet, C" uniqKey="Combet C" first="C" last="Combet">C. Combet</name><affiliation><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Zoulim, F" sort="Zoulim, F" uniqKey="Zoulim F" first="F" last="Zoulim">F. Zoulim</name><affiliation><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bronowicki, J P" sort="Bronowicki, J P" uniqKey="Bronowicki J" first="J-P" last="Bronowicki">J-P Bronowicki</name><affiliation><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Schvoerer, E" sort="Schvoerer, E" uniqKey="Schvoerer E" first="E" last="Schvoerer">E. Schvoerer</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26742490</idno><idno type="pmid">26742490</idno><idno type="doi">10.1111/jvh.12498</idno><idno type="wicri:Area/PubMed/Corpus">001E94</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001E94</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.</title><author><name sortKey="Velay, A" sort="Velay, A" uniqKey="Velay A" first="A" last="Velay">A. Velay</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Jeulin, H" sort="Jeulin, H" uniqKey="Jeulin H" first="H" last="Jeulin">H. Jeulin</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eschlimann, M" sort="Eschlimann, M" uniqKey="Eschlimann M" first="M" last="Eschlimann">M. Eschlimann</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Malve, B" sort="Malve, B" uniqKey="Malve B" first="B" last="Malvé">B. Malvé</name><affiliation><nlm:affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Goehringer, F" sort="Goehringer, F" uniqKey="Goehringer F" first="F" last="Goehringer">F. Goehringer</name><affiliation><nlm:affiliation>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bensenane, M" sort="Bensenane, M" uniqKey="Bensenane M" first="M" last="Bensenane">M. Bensenane</name><affiliation><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Frippiat, J P" sort="Frippiat, J P" uniqKey="Frippiat J" first="J-P" last="Frippiat">J-P Frippiat</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Abraham, P" sort="Abraham, P" uniqKey="Abraham P" first="P" last="Abraham">P. Abraham</name><affiliation><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation></affiliation></author><author><name sortKey="Ismail, A M" sort="Ismail, A M" uniqKey="Ismail A" first="A M" last="Ismail">A M Ismail</name><affiliation><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation></affiliation></author><author><name sortKey="Murray, J M" sort="Murray, J M" uniqKey="Murray J" first="J M" last="Murray">J M Murray</name><affiliation><nlm:affiliation>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Combet, C" sort="Combet, C" uniqKey="Combet C" first="C" last="Combet">C. Combet</name><affiliation><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Zoulim, F" sort="Zoulim, F" uniqKey="Zoulim F" first="F" last="Zoulim">F. Zoulim</name><affiliation><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bronowicki, J P" sort="Bronowicki, J P" uniqKey="Bronowicki J" first="J-P" last="Bronowicki">J-P Bronowicki</name><affiliation><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Schvoerer, E" sort="Schvoerer, E" uniqKey="Schvoerer E" first="E" last="Schvoerer">E. Schvoerer</name><affiliation><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of viral hepatitis</title><idno type="eISSN">1365-2893</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Animals</term><term>Antigenic Variation</term><term>Antiviral Agents (therapeutic use)</term><term>Computational Biology</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Genetic Variation</term><term>Hepatitis B Surface Antigens (genetics)</term><term>Hepatitis B Surface Antigens (immunology)</term><term>Hepatitis B, Chronic (drug therapy)</term><term>Humans</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Mutant Proteins (genetics)</term><term>Mutant Proteins (immunology)</term><term>Nucleosides (therapeutic use)</term><term>Nucleotides (therapeutic use)</term><term>Sequence Analysis, DNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hepatitis B Surface Antigens</term><term>Mutant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hepatitis B Surface Antigens</term><term>Mutant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Nucleosides</term><term>Nucleotides</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Hepatitis B, Chronic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Animals</term><term>Antigenic Variation</term><term>Computational Biology</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Genetic Variation</term><term>Humans</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Sequence Analysis, DNA</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26742490</PMID><DateCreated><Year>2016</Year><Month>04</Month><Day>18</Day></DateCreated><DateCompleted><Year>2016</Year><Month>12</Month><Day>19</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1365-2893</ISSN><JournalIssue CitedMedium="Internet"><Volume>23</Volume><Issue>5</Issue><PubDate><Year>2016</Year><Month>May</Month></PubDate></JournalIssue><Title>Journal of viral hepatitis</Title><ISOAbbreviation>J. Viral Hepat.</ISOAbbreviation></Journal><ArticleTitle>Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.</ArticleTitle><Pagination><MedlinePgn>387-98</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/jvh.12498</ELocationID><Abstract><AbstractText>For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.</AbstractText><CopyrightInformation>© 2016 John Wiley & Sons Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Velay</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeulin</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eschlimann</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malvé</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goehringer</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bensenane</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frippiat</LastName><ForeName>J-P</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abraham</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ismail</LastName><ForeName>A M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Murray</LastName><ForeName>J M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Combet</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zoulim</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bronowicki</LastName><ForeName>J-P</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schvoerer</LastName><ForeName>E</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>GENBANK</DataBankName><AccessionNumberList><AccessionNumber>AY161150</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Viral Hepat</MedlineTA><NlmUniqueID>9435672</NlmUniqueID><ISSNLinking>1352-0504</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral 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PubStatus="pubmed"><Year>2016</Year><Month>1</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>12</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26742490</ArticleId><ArticleId IdType="doi">10.1111/jvh.12498</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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