{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:45:03Z","timestamp":1761101103317},"reference-count":41,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hepatitis C virus genotype 4 (HCV-4) is the cause of approximately 20% of the 180 million cases of chronic hepatitis C in the world. HCV-4 infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. Viral genetic polymorphisms, especially within core and NS5A regions, have been implicated in influencing the response to pegylated-interferon and ribavirin (PEG-IFN\/RBV) combination therapy in HCV-1 infection. However, this has not been confirmed in HCV-4 infection. Here, we investigated the impact of heterogeneity of NS5A and core proteins of HCV-4, mostly subtype HCV-4a, on the clinical outcomes of 43 Egyptian patients treated with PEG-IFN\/RBV. Sliding window analysis over the carboxy terminus of NS5A protein identified the IFN\/RBV resistance-determining region (IRRDR) as the most prominent region associated with sustained virological response (SVR). Indeed, 21 (84%) of 25 patients with SVR, but only 5 (28%) of 18 patients with non-SVR, were infected with HCV having IRRDR with 4 or more mutations (IRRDR \u2265 4) (\n            <jats:italic>P<\/jats:italic>\n            = 0.0004). Multivariate analysis identified IRRDR \u2265 4 as an independent SVR predictor. The positive predictive value of IRRDR \u2265 4 for SVR was 81% (21\/26;\n            <jats:italic>P<\/jats:italic>\n            = 0.002), while its negative predictive value for non-SVR was 76% (13\/17;\n            <jats:italic>P<\/jats:italic>\n            = 0.02). On the other hand, there was no significant correlation between core protein polymorphisms, either at residue 70 or at residue 91, and treatment outcome. In conclusion, the present results demonstrate for the first time that IRRDR \u2265 4, a viral genetic heterogeneity, would be a useful predictive marker for SVR in HCV-4 infection when treated with PEG-IFN\/RBV.\n          <\/jats:p>","DOI":"10.1128\/jcm.02109-12","type":"journal-article","created":{"date-parts":[[2012,9,20]],"date-time":"2012-09-20T01:34:44Z","timestamp":1348104884000},"page":"3886-3892","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["NS5A Sequence Heterogeneity of Hepatitis C Virus Genotype 4a Predicts Clinical Outcome of Pegylated-Interferon\u2013Ribavirin Therapy in Egyptian Patients"],"prefix":"10.1128","volume":"50","author":[{"given":"Ahmed","family":"El-Shamy","sequence":"first","affiliation":[{"name":"Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan"},{"name":"Department of Virology, Suez Canal University Faculty of Veterinary Medicine, Ismalia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuo","family":"Shoji","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wafaa","family":"El-Akel","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shymaa E.","family":"Bilasy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Suez Canal University Faculty of Pharmacy, Ismalia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maissa","family":"El-Raziky","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-peng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gamal","family":"Esmat","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hak","family":"Hotta","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.8438"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82626-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000235909"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jhep.2006.09.019","article-title":"Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels","volume":"46","author":"Akuta N","year":"2007","unstructured":"AkutaN. 2007. Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J. Hepatol. 46:403\u2013410.","journal-title":"J. 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Hepatocellular carcinoma in Egypt: a single center study over a decade. World J. Gastroenterol. 11:5193\u20135198.","journal-title":"World J. 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Interferon therapy of hepatitis C: molecular insights into success and failure. Swiss Med. Wkly. 140:3\u201311.","journal-title":"Swiss Med. Wkly."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014463"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20819"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-11-2391"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.447"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2000.02112.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.449"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00792.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2009.01169.x"}],"container-title":["Journal of Clinical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.02109-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.02109-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T11:05:11Z","timestamp":1646478311000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JCM.02109-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1128\/JCM.02109-12"],"URL":"https:\/\/doi.org\/10.1128\/jcm.02109-12","relation":{},"ISSN":["0095-1137","1098-660X"],"issn-type":[{"value":"0095-1137","type":"print"},{"value":"1098-660X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12]]},"assertion":[{"value":"2012-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}