Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype1b and high viral load
Patients with high viral load (≥1.0 × 105 IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core regio...
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| Veröffentlicht in: | Journal of medical virology 2006-01, Vol.78 (1), p.83-90 |
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| creator | Akuta, Norio Suzuki, Fumitaka Sezaki, Hitomi Suzuki, Yoshiyuki Hosaka, Tetsuya Someya, Takashi Kobayashi, Masahiro Saitoh, Satoshi Watahiki, Sachiyo Sato, Junko Kobayashi, Mariko Arase, Yasuji Ikeda, Kenji Kumada, Hiromitsu |
| description | Patients with high viral load (≥1.0 × 105 IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non‐response especially in patients who could not achieve HCV‐RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for ≥24 weeks. A case‐control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non‐response, especially absolute virological non‐response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non‐response was identified in 26.3% of patients, and 45.5% of these were absolute virological non‐responders. Multivariate analysis identified ribavirin dose |
| doi_str_mv | 10.1002/jmv.20507 |
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Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non‐response especially in patients who could not achieve HCV‐RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for ≥24 weeks. A case‐control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non‐response, especially absolute virological non‐response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non‐response was identified in 26.3% of patients, and 45.5% of these were absolute virological non‐responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate‐to‐severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non‐response. The majority of absolute virological non‐responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non‐responders. The results suggest that viral, host, and treatment‐related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non‐response. J. Med. Virol. 78:83–90, 2006. © 2005 Wiley‐Liss, inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.20507</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>case- control study ; core region ; HCV ; Hepatitis C virus ; hepatocyte steatosis ; interferon ; ribavirin ; virological non-response</subject><ispartof>Journal of medical virology, 2006-01, Vol.78 (1), p.83-90</ispartof><rights>Copyright © 2005 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3737-f9dd32e6a8ce3ac67797fd8b232c1ec1b27b601052720a1daf064fc17d5353c43</citedby><cites>FETCH-LOGICAL-c3737-f9dd32e6a8ce3ac67797fd8b232c1ec1b27b601052720a1daf064fc17d5353c43</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.20507$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.20507$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Akuta, Norio</creatorcontrib><creatorcontrib>Suzuki, Fumitaka</creatorcontrib><creatorcontrib>Sezaki, Hitomi</creatorcontrib><creatorcontrib>Suzuki, Yoshiyuki</creatorcontrib><creatorcontrib>Hosaka, Tetsuya</creatorcontrib><creatorcontrib>Someya, Takashi</creatorcontrib><creatorcontrib>Kobayashi, Masahiro</creatorcontrib><creatorcontrib>Saitoh, Satoshi</creatorcontrib><creatorcontrib>Watahiki, Sachiyo</creatorcontrib><creatorcontrib>Sato, Junko</creatorcontrib><creatorcontrib>Kobayashi, Mariko</creatorcontrib><creatorcontrib>Arase, Yasuji</creatorcontrib><creatorcontrib>Ikeda, Kenji</creatorcontrib><creatorcontrib>Kumada, Hiromitsu</creatorcontrib><title>Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype1b and high viral load</title><title>Journal of medical virology</title><addtitle>J. Med. Virol</addtitle><description>Patients with high viral load (≥1.0 × 105 IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non‐response especially in patients who could not achieve HCV‐RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for ≥24 weeks. A case‐control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non‐response, especially absolute virological non‐response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non‐response was identified in 26.3% of patients, and 45.5% of these were absolute virological non‐responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate‐to‐severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non‐response. The majority of absolute virological non‐responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non‐responders. The results suggest that viral, host, and treatment‐related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non‐response. J. Med. Virol. 78:83–90, 2006. © 2005 Wiley‐Liss, inc.</description><subject>case- control study</subject><subject>core region</subject><subject>HCV</subject><subject>Hepatitis C virus</subject><subject>hepatocyte steatosis</subject><subject>interferon</subject><subject>ribavirin</subject><subject>virological non-response</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNp1kctuEzEUhi0EEqGw4A28QmIxrS8zdmaJAgSqEkAqsLQ89nHGZWJPbSclj8RbdqYBdqyOdM73n9uP0EtKzikh7OJmdzhnpCHyEVpQ0oqqJZI-RgtCa1EJQZun6FnON4SQZcvYAv3-ksB6U_wBsNOmxJRxdPjgUxzi1hs94BBDlSCPMWTAJWIfCiQHaU77Tk-oD9jEXeeDLj4GXHpIejxiFxMepxSEkieVA1PA4jtfetzDXCg-49U8a_8wdAshluMItMM6WNz7bT8XpxWGqO1z9MTpIcOLP_EMfXv_7nr1obr6vP64enNVGS65rFxrLWcg9NIA10ZI2Upnlx3jzFAwtGOyE4SShklGNLXaEVE7Q6VteMNNzc_Qq1PfMcXbPeSidj4bGAYdIO6zmr7LWl7P4OsTaFLMOYFTY_I7nY6KEjWboSYz1IMZE3txYu_8AMf_g-ry0_e_iuqk8LnAr38KnX4qMd3ZqB-btaoJ__p2s96oa34PasCfhA</recordid><startdate>200601</startdate><enddate>200601</enddate><creator>Akuta, Norio</creator><creator>Suzuki, Fumitaka</creator><creator>Sezaki, Hitomi</creator><creator>Suzuki, Yoshiyuki</creator><creator>Hosaka, Tetsuya</creator><creator>Someya, Takashi</creator><creator>Kobayashi, Masahiro</creator><creator>Saitoh, Satoshi</creator><creator>Watahiki, Sachiyo</creator><creator>Sato, Junko</creator><creator>Kobayashi, Mariko</creator><creator>Arase, Yasuji</creator><creator>Ikeda, Kenji</creator><creator>Kumada, Hiromitsu</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>200601</creationdate><title>Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype1b and high viral load</title><author>Akuta, Norio ; Suzuki, Fumitaka ; Sezaki, Hitomi ; Suzuki, Yoshiyuki ; Hosaka, Tetsuya ; Someya, Takashi ; Kobayashi, Masahiro ; Saitoh, Satoshi ; Watahiki, Sachiyo ; Sato, Junko ; Kobayashi, Mariko ; Arase, Yasuji ; Ikeda, Kenji ; Kumada, Hiromitsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3737-f9dd32e6a8ce3ac67797fd8b232c1ec1b27b601052720a1daf064fc17d5353c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>case- control study</topic><topic>core region</topic><topic>HCV</topic><topic>Hepatitis C virus</topic><topic>hepatocyte steatosis</topic><topic>interferon</topic><topic>ribavirin</topic><topic>virological non-response</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akuta, Norio</creatorcontrib><creatorcontrib>Suzuki, Fumitaka</creatorcontrib><creatorcontrib>Sezaki, Hitomi</creatorcontrib><creatorcontrib>Suzuki, Yoshiyuki</creatorcontrib><creatorcontrib>Hosaka, Tetsuya</creatorcontrib><creatorcontrib>Someya, Takashi</creatorcontrib><creatorcontrib>Kobayashi, Masahiro</creatorcontrib><creatorcontrib>Saitoh, Satoshi</creatorcontrib><creatorcontrib>Watahiki, Sachiyo</creatorcontrib><creatorcontrib>Sato, Junko</creatorcontrib><creatorcontrib>Kobayashi, Mariko</creatorcontrib><creatorcontrib>Arase, Yasuji</creatorcontrib><creatorcontrib>Ikeda, Kenji</creatorcontrib><creatorcontrib>Kumada, Hiromitsu</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akuta, Norio</au><au>Suzuki, Fumitaka</au><au>Sezaki, Hitomi</au><au>Suzuki, Yoshiyuki</au><au>Hosaka, Tetsuya</au><au>Someya, Takashi</au><au>Kobayashi, Masahiro</au><au>Saitoh, Satoshi</au><au>Watahiki, Sachiyo</au><au>Sato, Junko</au><au>Kobayashi, Mariko</au><au>Arase, Yasuji</au><au>Ikeda, Kenji</au><au>Kumada, Hiromitsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype1b and high viral load</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J. Med. Virol</addtitle><date>2006-01</date><risdate>2006</risdate><volume>78</volume><issue>1</issue><spage>83</spage><epage>90</epage><pages>83-90</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>Patients with high viral load (≥1.0 × 105 IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non‐response especially in patients who could not achieve HCV‐RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for ≥24 weeks. A case‐control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non‐response, especially absolute virological non‐response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non‐response was identified in 26.3% of patients, and 45.5% of these were absolute virological non‐responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate‐to‐severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non‐response. The majority of absolute virological non‐responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non‐responders. The results suggest that viral, host, and treatment‐related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non‐response. J. Med. Virol. 78:83–90, 2006. © 2005 Wiley‐Liss, inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><doi>10.1002/jmv.20507</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | case- control study core region HCV Hepatitis C virus hepatocyte steatosis interferon ribavirin virological non-response |
| title | Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype1b and high viral load |
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