Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance
The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interfe...
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| Veröffentlicht in: | Journal of medical virology 2007-08, Vol.79 (8), p.1055-1063 |
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| creator | Hou, Jinlin Schilling, Ralf Janssen, Harry L. A. Hansen, Bettina E. Heijtink, Rudolf Sablon, Erwin Williams, Roger Lau, George K.K. Schalm, Solko W. Naoumov, Nikolai V. |
| description | The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon‐alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO‐LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16‐weeks interferon‐alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16‐weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P |
| doi_str_mv | 10.1002/jmv.20935 |
| format | Article |
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A. ; Hansen, Bettina E. ; Heijtink, Rudolf ; Sablon, Erwin ; Williams, Roger ; Lau, George K.K. ; Schalm, Solko W. ; Naoumov, Nikolai V.</creator><creatorcontrib>Hou, Jinlin ; Schilling, Ralf ; Janssen, Harry L. A. ; Hansen, Bettina E. ; Heijtink, Rudolf ; Sablon, Erwin ; Williams, Roger ; Lau, George K.K. ; Schalm, Solko W. ; Naoumov, Nikolai V.</creatorcontrib><description>The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon‐alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO‐LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16‐weeks interferon‐alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16‐weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94–19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon‐alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon‐based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055–1063, 2007. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.20935</identifier><identifier>PMID: 17596838</identifier><identifier>CODEN: JMVIDB</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Biological and medical sciences ; chronic hepatitis B ; core promoter mutations ; Female ; Fundamental and applied biological sciences. Psychology ; Genetics ; Genome, Viral ; Genotype ; HBV genotypes ; Hepatitis B e Antigens - blood ; Hepatitis B e Antigens - genetics ; Hepatitis B e Antigens - metabolism ; Hepatitis B virus ; Hepatitis B virus - genetics ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - virology ; Humans ; Interferon-alpha - pharmacology ; Interferon-alpha - therapeutic use ; interferon-alpha treatment ; Male ; Microbiology ; Middle Aged ; Mutation ; precore stop codon ; Promoter Regions, Genetic - genetics ; Viral Core Proteins - genetics ; Virology</subject><ispartof>Journal of medical virology, 2007-08, Vol.79 (8), p.1055-1063</ispartof><rights>Copyright © 2007 Wiley‐Liss, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4885-a1be1c55d498e1d4c96cd056effdd59db102c4507370e95a16925d136c6202e13</citedby><cites>FETCH-LOGICAL-c4885-a1be1c55d498e1d4c96cd056effdd59db102c4507370e95a16925d136c6202e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.20935$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.20935$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18866892$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17596838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Jinlin</creatorcontrib><creatorcontrib>Schilling, Ralf</creatorcontrib><creatorcontrib>Janssen, Harry L. A.</creatorcontrib><creatorcontrib>Hansen, Bettina E.</creatorcontrib><creatorcontrib>Heijtink, Rudolf</creatorcontrib><creatorcontrib>Sablon, Erwin</creatorcontrib><creatorcontrib>Williams, Roger</creatorcontrib><creatorcontrib>Lau, George K.K.</creatorcontrib><creatorcontrib>Schalm, Solko W.</creatorcontrib><creatorcontrib>Naoumov, Nikolai V.</creatorcontrib><title>Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance</title><title>Journal of medical virology</title><addtitle>J. Med. Virol</addtitle><description>The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon‐alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO‐LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16‐weeks interferon‐alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16‐weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94–19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon‐alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon‐based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055–1063, 2007. © 2007 Wiley‐Liss, Inc.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>chronic hepatitis B</subject><subject>core promoter mutations</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. 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A.</creator><creator>Hansen, Bettina E.</creator><creator>Heijtink, Rudolf</creator><creator>Sablon, Erwin</creator><creator>Williams, Roger</creator><creator>Lau, George K.K.</creator><creator>Schalm, Solko W.</creator><creator>Naoumov, Nikolai V.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200708</creationdate><title>Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance</title><author>Hou, Jinlin ; Schilling, Ralf ; Janssen, Harry L. 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A.</au><au>Hansen, Bettina E.</au><au>Heijtink, Rudolf</au><au>Sablon, Erwin</au><au>Williams, Roger</au><au>Lau, George K.K.</au><au>Schalm, Solko W.</au><au>Naoumov, Nikolai V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J. Med. Virol</addtitle><date>2007-08</date><risdate>2007</risdate><volume>79</volume><issue>8</issue><spage>1055</spage><epage>1063</epage><pages>1055-1063</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><coden>JMVIDB</coden><abstract>The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon‐alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO‐LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16‐weeks interferon‐alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16‐weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94–19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon‐alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon‐based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055–1063, 2007. © 2007 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17596838</pmid><doi>10.1002/jmv.20935</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences chronic hepatitis B core promoter mutations Female Fundamental and applied biological sciences. Psychology Genetics Genome, Viral Genotype HBV genotypes Hepatitis B e Antigens - blood Hepatitis B e Antigens - genetics Hepatitis B e Antigens - metabolism Hepatitis B virus Hepatitis B virus - genetics Hepatitis B, Chronic - drug therapy Hepatitis B, Chronic - virology Humans Interferon-alpha - pharmacology Interferon-alpha - therapeutic use interferon-alpha treatment Male Microbiology Middle Aged Mutation precore stop codon Promoter Regions, Genetic - genetics Viral Core Proteins - genetics Virology |
| title | Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance |
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