Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis
The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver‐related death in patients of hepatitis C virus (HCV) genotype 1b (HCV‐1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, a...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2012-12, Vol.56 (6), p.2134-2141 |
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| creator | Akuta, Norio Suzuki, Fumitaka Seko, Yuya Kawamura, Yusuke Sezaki, Hitomi Suzuki, Yoshiyuki Hosaka, Tetsuya Kobayashi, Masahiro Hara, Tasuku Kobayashi, Mariko Saitoh, Satoshi Arase, Yasuji Ikeda, Kenji Kumada, Hiromitsu |
| description | The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver‐related death in patients of hepatitis C virus (HCV) genotype 1b (HCV‐1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV‐infected patients, who had not received antiviral therapy, were included in a follow‐up study to determine predictive factors of hepatocarcinogenesis and survival for liver‐related death. The cumulative hepatocarcinogenesis rates in HCV‐1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV‐1b of Arg70 (arginine at aa 70) and HCV‐2a/2b. The cumulative survival rates for liver‐related death in HCV‐1b of Gln70(His70) were significantly lower than those in HCV‐1b of Arg70 and HCV‐2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin ( |
| doi_str_mv | 10.1002/hep.25949 |
| format | Article |
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The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV‐infected patients, who had not received antiviral therapy, were included in a follow‐up study to determine predictive factors of hepatocarcinogenesis and survival for liver‐related death. The cumulative hepatocarcinogenesis rates in HCV‐1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV‐1b of Arg70 (arginine at aa 70) and HCV‐2a/2b. The cumulative survival rates for liver‐related death in HCV‐1b of Gln70(His70) were significantly lower than those in HCV‐1b of Arg70 and HCV‐2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 104/mm3), aspartate aminotransferase (≥67 IU/L), and HCV subgroup (HCV‐1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver‐related death. In HCV‐1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non‐TT genotype were significantly higher than those in the TT genotype. Conclusion: Substitution of aa 70 in the core region of HCV‐1b is an important predictor of hepatocarcinogenesis and survival for liver‐related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV‐1b. (HEPATOLOGY 2012;56:2134–2141)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.25949</identifier><identifier>PMID: 22806754</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - virology ; Cell Transformation, Neoplastic - genetics ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Genotype ; Hepacivirus - genetics ; Hepacivirus - metabolism ; Hepatitis ; Hepatitis C ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - genetics ; Hepatitis C, Chronic - metabolism ; Hepatology ; Humans ; Interferons ; Interleukins - genetics ; Kaplan-Meier Estimate ; Liver Neoplasms - pathology ; Liver Neoplasms - virology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Survival Rate ; Tumors ; Viral Core Proteins - metabolism ; Young Adult</subject><ispartof>Hepatology (Baltimore, Md.), 2012-12, Vol.56 (6), p.2134-2141</ispartof><rights>Copyright © 2012 American Association for the Study of Liver Diseases</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3879-d5a60cdcc2fe3ac823cc9ad77ed10c2e6d081b373c26b7952a4c5508bfcd623</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.25949$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.25949$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26853024$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22806754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akuta, Norio</creatorcontrib><creatorcontrib>Suzuki, Fumitaka</creatorcontrib><creatorcontrib>Seko, Yuya</creatorcontrib><creatorcontrib>Kawamura, Yusuke</creatorcontrib><creatorcontrib>Sezaki, Hitomi</creatorcontrib><creatorcontrib>Suzuki, Yoshiyuki</creatorcontrib><creatorcontrib>Hosaka, Tetsuya</creatorcontrib><creatorcontrib>Kobayashi, Masahiro</creatorcontrib><creatorcontrib>Hara, Tasuku</creatorcontrib><creatorcontrib>Kobayashi, Mariko</creatorcontrib><creatorcontrib>Saitoh, Satoshi</creatorcontrib><creatorcontrib>Arase, Yasuji</creatorcontrib><creatorcontrib>Ikeda, Kenji</creatorcontrib><creatorcontrib>Kumada, Hiromitsu</creatorcontrib><title>Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver‐related death in patients of hepatitis C virus (HCV) genotype 1b (HCV‐1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV‐infected patients, who had not received antiviral therapy, were included in a follow‐up study to determine predictive factors of hepatocarcinogenesis and survival for liver‐related death. The cumulative hepatocarcinogenesis rates in HCV‐1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV‐1b of Arg70 (arginine at aa 70) and HCV‐2a/2b. The cumulative survival rates for liver‐related death in HCV‐1b of Gln70(His70) were significantly lower than those in HCV‐1b of Arg70 and HCV‐2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 104/mm3), aspartate aminotransferase (≥67 IU/L), and HCV subgroup (HCV‐1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver‐related death. In HCV‐1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non‐TT genotype were significantly higher than those in the TT genotype. Conclusion: Substitution of aa 70 in the core region of HCV‐1b is an important predictor of hepatocarcinogenesis and survival for liver‐related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV‐1b. (HEPATOLOGY 2012;56:2134–2141)</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amino Acid Substitution</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genotype</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - metabolism</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - genetics</subject><subject>Hepatitis C, Chronic - metabolism</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Interferons</subject><subject>Interleukins - genetics</subject><subject>Kaplan-Meier Estimate</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - virology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Proportional Hazards Models</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Viral Core Proteins - metabolism</subject><subject>Young Adult</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkdtuEzEQQC0EomnhgR9AlhCP2_qyvj22oTcpAiRQeLS8tjd1u1kv9i5tPqF_XadJy9N4NOfMyDMAfMLoGCNETm78cEyYqtUbMMOMiIpSht6CGSICVQpTdQAOc75FCKmayPfggBCJuGD1DDzO43rogjWjdzD5zowh9vkmDBnGFpp16CM0NjiYpyaPYZy2dRh6WGYWdgwZzuG_kKYMbUy-tFhtAdM7eL0g8gyufB_HzeCL03aT723oVzs5WpNKFgvhc8gfwLvWdNl_3Mcj8Ovi_Pf8qlr8uLyeny4qS6VQlWOGI-usJa2nxkpCrVXGCeEdRpZ47pDEDRXUEt4IxYipLWNINq11nNAj8GXXdUjx7-TzqG_jlPoyUGNCMOOslqpQn_fU1Ky900MKa5M2-mVvBfi6B0y2pmuTKR_L_zkuGUVky53suPvQ-c1rHSO9PZwue9DPh9NX5z-fH8WodkbIo394NUy601xQwfSf75f6m8BLsVhyvaRPK8-cNA</recordid><startdate>201212</startdate><enddate>201212</enddate><creator>Akuta, Norio</creator><creator>Suzuki, Fumitaka</creator><creator>Seko, Yuya</creator><creator>Kawamura, Yusuke</creator><creator>Sezaki, Hitomi</creator><creator>Suzuki, Yoshiyuki</creator><creator>Hosaka, Tetsuya</creator><creator>Kobayashi, Masahiro</creator><creator>Hara, Tasuku</creator><creator>Kobayashi, Mariko</creator><creator>Saitoh, Satoshi</creator><creator>Arase, Yasuji</creator><creator>Ikeda, Kenji</creator><creator>Kumada, Hiromitsu</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wolters Kluwer Health, Inc</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201212</creationdate><title>Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis</title><author>Akuta, Norio ; Suzuki, Fumitaka ; Seko, Yuya ; Kawamura, Yusuke ; Sezaki, Hitomi ; Suzuki, Yoshiyuki ; Hosaka, Tetsuya ; Kobayashi, Masahiro ; Hara, Tasuku ; Kobayashi, Mariko ; Saitoh, Satoshi ; Arase, Yasuji ; Ikeda, Kenji ; Kumada, Hiromitsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3879-d5a60cdcc2fe3ac823cc9ad77ed10c2e6d081b373c26b7952a4c5508bfcd623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amino Acid Substitution</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genotype</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - metabolism</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - genetics</topic><topic>Hepatitis C, Chronic - metabolism</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Interferons</topic><topic>Interleukins - genetics</topic><topic>Kaplan-Meier Estimate</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - virology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Proportional Hazards Models</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Viral Core Proteins - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akuta, Norio</creatorcontrib><creatorcontrib>Suzuki, Fumitaka</creatorcontrib><creatorcontrib>Seko, Yuya</creatorcontrib><creatorcontrib>Kawamura, Yusuke</creatorcontrib><creatorcontrib>Sezaki, Hitomi</creatorcontrib><creatorcontrib>Suzuki, Yoshiyuki</creatorcontrib><creatorcontrib>Hosaka, Tetsuya</creatorcontrib><creatorcontrib>Kobayashi, Masahiro</creatorcontrib><creatorcontrib>Hara, Tasuku</creatorcontrib><creatorcontrib>Kobayashi, Mariko</creatorcontrib><creatorcontrib>Saitoh, Satoshi</creatorcontrib><creatorcontrib>Arase, Yasuji</creatorcontrib><creatorcontrib>Ikeda, Kenji</creatorcontrib><creatorcontrib>Kumada, Hiromitsu</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akuta, Norio</au><au>Suzuki, Fumitaka</au><au>Seko, Yuya</au><au>Kawamura, Yusuke</au><au>Sezaki, Hitomi</au><au>Suzuki, Yoshiyuki</au><au>Hosaka, Tetsuya</au><au>Kobayashi, Masahiro</au><au>Hara, Tasuku</au><au>Kobayashi, Mariko</au><au>Saitoh, Satoshi</au><au>Arase, Yasuji</au><au>Ikeda, Kenji</au><au>Kumada, Hiromitsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2012-12</date><risdate>2012</risdate><volume>56</volume><issue>6</issue><spage>2134</spage><epage>2141</epage><pages>2134-2141</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver‐related death in patients of hepatitis C virus (HCV) genotype 1b (HCV‐1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV‐infected patients, who had not received antiviral therapy, were included in a follow‐up study to determine predictive factors of hepatocarcinogenesis and survival for liver‐related death. The cumulative hepatocarcinogenesis rates in HCV‐1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV‐1b of Arg70 (arginine at aa 70) and HCV‐2a/2b. The cumulative survival rates for liver‐related death in HCV‐1b of Gln70(His70) were significantly lower than those in HCV‐1b of Arg70 and HCV‐2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 104/mm3), aspartate aminotransferase (≥67 IU/L), and HCV subgroup (HCV‐1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver‐related death. In HCV‐1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non‐TT genotype were significantly higher than those in the TT genotype. Conclusion: Substitution of aa 70 in the core region of HCV‐1b is an important predictor of hepatocarcinogenesis and survival for liver‐related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV‐1b. (HEPATOLOGY 2012;56:2134–2141)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22806754</pmid><doi>10.1002/hep.25949</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Amino Acid Substitution Antiviral Agents - therapeutic use Biological and medical sciences Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - virology Cell Transformation, Neoplastic - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Genotype Hepacivirus - genetics Hepacivirus - metabolism Hepatitis Hepatitis C Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - genetics Hepatitis C, Chronic - metabolism Hepatology Humans Interferons Interleukins - genetics Kaplan-Meier Estimate Liver Neoplasms - pathology Liver Neoplasms - virology Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Multivariate Analysis Proportional Hazards Models Survival Rate Tumors Viral Core Proteins - metabolism Young Adult |
| title | Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis |
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