Role of IL28B for chronic hepatitis C treatment toward personalized medicine
Genome‐wide association studies recently revealed that certain interleukin‐28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG‐IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1, as well as with spontane...
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Veröffentlicht in: | Journal of gastroenterology and hepatology 2014-02, Vol.29 (2), p.241-249 |
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description | Genome‐wide association studies recently revealed that certain interleukin‐28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG‐IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1, as well as with spontaneous clearance of HCV. Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC). Therapy of CHC recently entered a new era with the deployment of direct‐acting antivirals. These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG‐IFN/RBV in several clinical trials. IFN‐free therapy is expected to be useful especially in IFN‐resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy or IFN‐free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the polymorphism of IFN‐lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B, and more strongly associated with spontaneous or treatment‐induced HCV clearance than IL28B genotypes, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of direct‐acting antivirals. |
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Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC). Therapy of CHC recently entered a new era with the deployment of direct‐acting antivirals. These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG‐IFN/RBV in several clinical trials. IFN‐free therapy is expected to be useful especially in IFN‐resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy or IFN‐free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the polymorphism of IFN‐lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B, and more strongly associated with spontaneous or treatment‐induced HCV clearance than IL28B genotypes, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of direct‐acting antivirals.</description><identifier>ISSN: 0815-9319</identifier><identifier>EISSN: 1440-1746</identifier><identifier>DOI: 10.1111/jgh.12475</identifier><identifier>PMID: 24325405</identifier><language>eng</language><publisher>Australia: Blackwell Publishing Ltd</publisher><subject>Antiviral Agents - therapeutic use ; direct-acting antiviral (DAA) ; Genome-Wide Association Study ; genome-wide association study (GWAS) ; Genotype ; Hepacivirus - genetics ; Hepatitis C virus ; hepatitis C virus (HCV) ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - genetics ; Hepatitis C, Chronic - virology ; Humans ; Interferon alpha-2 ; Interferon-alpha - therapeutic use ; Interferons ; interleukin 28B (IL28B) ; Interleukins - genetics ; Polyethylene Glycols - therapeutic use ; Polymorphism, Genetic ; Precision Medicine ; Recombinant Proteins - therapeutic use ; Ribavirin - therapeutic use ; Treatment Outcome</subject><ispartof>Journal of gastroenterology and hepatology, 2014-02, Vol.29 (2), p.241-249</ispartof><rights>2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd</rights><rights>2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4625-37c37ec15fab1f0eabc6b91f60971af98b90f3ac4f60bcb771b752a98edd46d73</citedby><cites>FETCH-LOGICAL-c4625-37c37ec15fab1f0eabc6b91f60971af98b90f3ac4f60bcb771b752a98edd46d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjgh.12475$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjgh.12475$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24325405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsuura, Kentaro</creatorcontrib><creatorcontrib>Watanabe, Tsunamasa</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><title>Role of IL28B for chronic hepatitis C treatment toward personalized medicine</title><title>Journal of gastroenterology and hepatology</title><addtitle>J Gastroenterol Hepatol</addtitle><description>Genome‐wide association studies recently revealed that certain interleukin‐28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG‐IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1, as well as with spontaneous clearance of HCV. Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC). Therapy of CHC recently entered a new era with the deployment of direct‐acting antivirals. These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG‐IFN/RBV in several clinical trials. IFN‐free therapy is expected to be useful especially in IFN‐resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy or IFN‐free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the polymorphism of IFN‐lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B, and more strongly associated with spontaneous or treatment‐induced HCV clearance than IL28B genotypes, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of direct‐acting antivirals.</description><subject>Antiviral Agents - therapeutic use</subject><subject>direct-acting antiviral (DAA)</subject><subject>Genome-Wide Association Study</subject><subject>genome-wide association study (GWAS)</subject><subject>Genotype</subject><subject>Hepacivirus - genetics</subject><subject>Hepatitis C virus</subject><subject>hepatitis C virus (HCV)</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - genetics</subject><subject>Hepatitis C, Chronic - virology</subject><subject>Humans</subject><subject>Interferon alpha-2</subject><subject>Interferon-alpha - therapeutic use</subject><subject>Interferons</subject><subject>interleukin 28B (IL28B)</subject><subject>Interleukins - genetics</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Polymorphism, Genetic</subject><subject>Precision Medicine</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Ribavirin - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0815-9319</issn><issn>1440-1746</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOwzAQRS0EoqWw4AeQl7AI2LEdN0taQSmqQLyXluOMqUsaFzsVj68nUMqO2Yw0OvdKcxDap-SYtnMye54e05RLsYG6lHOSUMmzTdQlfSqSnNG8g3ZinBFCOJFiG3VSzlLBieiiya2vAHuLx5O0P8DWB2ymwdfO4CksdOMaF_EQNwF0M4e6wY1_06HECwjR17pyn1DiOZTOuBp20ZbVVYS9391DD-dn98OLZHI9Gg9PJ4nhWSoSJg2TYKiwuqCWgC5MVuTUZiSXVNu8X-TEMm14eylMISUtpEh13oey5FkpWQ8drnoXwb8uITZq7qKBqtI1-GVUVBDBUikz0qJHK9QEH2MAqxbBzXX4UJSob3mqlad-5LXswW_tsmhf-iPXtlrgZAW8uQo-_m9Sl6OLdWWySrjYwPtfQocXlUnWkk9XI3X7yAbs7makBPsCzrKHiw</recordid><startdate>201402</startdate><enddate>201402</enddate><creator>Matsuura, Kentaro</creator><creator>Watanabe, Tsunamasa</creator><creator>Tanaka, Yasuhito</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7U9</scope><scope>H94</scope></search><sort><creationdate>201402</creationdate><title>Role of IL28B for chronic hepatitis C treatment toward personalized medicine</title><author>Matsuura, Kentaro ; Watanabe, Tsunamasa ; Tanaka, Yasuhito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4625-37c37ec15fab1f0eabc6b91f60971af98b90f3ac4f60bcb771b752a98edd46d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antiviral Agents - therapeutic use</topic><topic>direct-acting antiviral (DAA)</topic><topic>Genome-Wide Association Study</topic><topic>genome-wide association study (GWAS)</topic><topic>Genotype</topic><topic>Hepacivirus - genetics</topic><topic>Hepatitis C virus</topic><topic>hepatitis C virus (HCV)</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - genetics</topic><topic>Hepatitis C, Chronic - virology</topic><topic>Humans</topic><topic>Interferon alpha-2</topic><topic>Interferon-alpha - therapeutic use</topic><topic>Interferons</topic><topic>interleukin 28B (IL28B)</topic><topic>Interleukins - genetics</topic><topic>Polyethylene Glycols - therapeutic use</topic><topic>Polymorphism, Genetic</topic><topic>Precision Medicine</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Ribavirin - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsuura, Kentaro</creatorcontrib><creatorcontrib>Watanabe, Tsunamasa</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsuura, Kentaro</au><au>Watanabe, Tsunamasa</au><au>Tanaka, Yasuhito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of IL28B for chronic hepatitis C treatment toward personalized medicine</atitle><jtitle>Journal of gastroenterology and hepatology</jtitle><addtitle>J Gastroenterol Hepatol</addtitle><date>2014-02</date><risdate>2014</risdate><volume>29</volume><issue>2</issue><spage>241</spage><epage>249</epage><pages>241-249</pages><issn>0815-9319</issn><eissn>1440-1746</eissn><abstract>Genome‐wide association studies recently revealed that certain interleukin‐28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG‐IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1, as well as with spontaneous clearance of HCV. Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC). Therapy of CHC recently entered a new era with the deployment of direct‐acting antivirals. These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG‐IFN/RBV in several clinical trials. IFN‐free therapy is expected to be useful especially in IFN‐resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy or IFN‐free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the polymorphism of IFN‐lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B, and more strongly associated with spontaneous or treatment‐induced HCV clearance than IL28B genotypes, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of direct‐acting antivirals.</abstract><cop>Australia</cop><pub>Blackwell Publishing Ltd</pub><pmid>24325405</pmid><doi>10.1111/jgh.12475</doi><tpages>9</tpages></addata></record> |
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subjects | Antiviral Agents - therapeutic use direct-acting antiviral (DAA) Genome-Wide Association Study genome-wide association study (GWAS) Genotype Hepacivirus - genetics Hepatitis C virus hepatitis C virus (HCV) Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - genetics Hepatitis C, Chronic - virology Humans Interferon alpha-2 Interferon-alpha - therapeutic use Interferons interleukin 28B (IL28B) Interleukins - genetics Polyethylene Glycols - therapeutic use Polymorphism, Genetic Precision Medicine Recombinant Proteins - therapeutic use Ribavirin - therapeutic use Treatment Outcome |
title | Role of IL28B for chronic hepatitis C treatment toward personalized medicine |
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