{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:56:01Z","timestamp":1786978561194,"version":"build-2736575974"},"reference-count":109,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006469","name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia","doi-asserted-by":"publisher","award":["ID 22976"],"award-info":[{"award-number":["ID 22976"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reviews in Medical Virology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Author Contribution<\/jats:title>\n                    <jats:p>FN performed the literature review and wrote the manuscript; STZ coauthored, edited, and reviewed the manuscript.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Treatment response in Hepatitis C virus (HCV) has generated varied effects in patients. Recently, nonresponsive and relapse patients related to host and genotype variabilities have been reported in clinical trials. However, these trials included minimal sample sizes of patients with genotype 4, the most prevalent genotype in Egypt and the Middle East, compared with genotypes 1 and 2. The genetic variabilities that have been detected within the HCV genes, especially the ones associated with genotype 4, and are linked to treatment response, will be the focus of this review with emphasis on direct acting antiviral agents. In addition, the major studies and clinical trials performed globally and their inclusivity of genotype 4 are reported. This review also delineates future study areas and missing data that need further investigation when it comes to genotype 4.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rmv.2120","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T08:26:47Z","timestamp":1591000007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatitis C genotype 4: A report on resistance\u2010associated substitutions in\n                    <scp>\n                      <i>NS3<\/i>\n                    <\/scp>\n                    ,\n                    <scp>\n                      <i>NS5A<\/i>\n                      ,\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>NS5B<\/i>\n                    <\/scp>\n                    genes"],"prefix":"10.1002","volume":"30","author":[{"given":"Nahla","family":"Fadl","sequence":"first","affiliation":[{"name":"Biomedical Sciences Program University of Science and Technology, Zewail City of Science and Technology  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-5037","authenticated-orcid":false,"given":"Tamer Z.","family":"Salem","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Program University of Science and Technology, Zewail City of Science and Technology  Giza Egypt"},{"name":"Department of Microbial Genetics AGERI, ARC  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2523562"},{"key":"e_1_2_9_3_1","volume-title":"HCV 5\u2032 and 3\u2032UTR: when Translation Meets Replication","author":"Shi ST","year":"2006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-27340-7_5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(04)63002-8"},{"key":"e_1_2_9_6_1","unstructured":"World Health Organisation.Hepatitis C fact sheet.https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/hepatitis-cAccessed May 16 2019."},{"key":"e_1_2_9_7_1","unstructured":"International Committee on Taxonomy of Viruses (ICTV).Confirmed HCV genotypes\/subtypes.https:\/\/talk.ictvonline.org\/ictv_wikis\/flaviviridae\/w\/sg_flavi\/634\/table-1-confirmed-hcv-genotypes-subtypes-may-2019. Accessed April 22 2020."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-27340-7_1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i34.7824"},{"issue":"3","key":"e_1_2_9_10_1","first-page":"199","article-title":"Hepatitis C virus infection and risk factors in health\u2010care workers at Ain Shams University Hospitals, Cairo","volume":"21","author":"Okasha O","year":"2015","journal-title":"Egypt East Mediterr Health J"},{"key":"e_1_2_9_11_1","unstructured":"WanisH.HCV treatment in Egypt\u2014why cost remains a challenge? Egyptian Initiative for Personal Rights.https:\/\/eipr.org\/en\/publications\/hepatitis-c-treatment-egypt-why-cost-remains-challengeAccessed June 10 2019."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27259"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24921"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82626-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.26719\/2018.24.7.609"},{"key":"e_1_2_9_16_1","unstructured":"EASL2011.Hep.https:\/\/www.hepmag.com\/tag\/easl-2011. Accessed November 10 2018."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12422"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26371"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21159"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22759"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.631"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.09.011"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.04.003"},{"key":"e_1_2_9_24_1","unstructured":"AASLD.HCV resistance primer|HCV guidance.https:\/\/www.hcvguidelines.org\/evaluate\/resistance. Accessed April 25 2020."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21303-2"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00731"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0395"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.20546\/ijcmas.2017.607.282"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.09.019"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-009-0087-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-009-0126-7"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.6b00110"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13117"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5424.107"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i17.2416"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067254"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00884-09"},{"key":"e_1_2_9_38_1","first-page":"1","article-title":"New insight into HCV E1\/E2 region of genotype 4a","volume":"11","author":"Hussein N","year":"2015","journal-title":"J Virol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i6.831"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.14740\/gr999w"},{"issue":"3","key":"e_1_2_9_41_1","first-page":"103","article-title":"Understanding hepatitis C virus drug resistance: clinical implications for current and future regimens","volume":"25","author":"Wyles DL","year":"2017","journal-title":"Top Antivir Med"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.18683\/germs.2017.1107"},{"key":"e_1_2_9_43_1","unstructured":"Antiviral Resistance Testing in the Management of Hepatitis C Virus Infection.https:\/\/www.gov.uk\/government\/publications\/antiviral-resistance-testing-in-the-management-of-hepatitis-c. Accessed August 5 2019."},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis761"},{"key":"e_1_2_9_45_1","first-page":"S478","article-title":"Daclatasvir, an NS5A replication complex inhibitor, combined with peginterferon Alfa\u20102a and ribavirin in treatmentnaive HCV\u2010genotype 1 or 4 patients: phase 2b COMMAND\u20101 SVR12","volume":"533","author":"Hezode C","year":"2012","journal-title":"J Hepatol"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2985"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.031"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214853"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60159-3"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.044"},{"key":"e_1_2_9_51_1","unstructured":"Sofosbuvir Plus Ribavirin in Treatment\u2010Naive and Treatment\u2010Experienced Egyptian Adults With Chronic Genotype 4 hepatitis C Virus (HCV) Infection\u2014Study Results.ClinicalTrials.gov.https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT01713283?term=Genotype+4+AND+Virologic+Response&recrs=e&rslt=With&cond=Hepatitis+C&draw=2&rank=9. Accessed April 23 2020."},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14509"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62483-1"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00157-7"},{"key":"e_1_2_9_55_1","unstructured":"Sofosbuvir Plus Ribavirin Administered for Either 12 or 24\u2009Weeks in Treatment\u2010Naive and Treatment\u2010Experienced Egyptian Adults With Chronic Genotype 4 HEPATITIS C Virus (HCV) Infection\u2014Full Text View.ClinicalTrials.gov.https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT01838590?term=Genotype+4+AND+Virologic+Response&recrs=e&rslt=With&cond=Hepatitis+C&draw=2&rank=5. Accessed April 23 2020."},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168713"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12801"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00052-9"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3184"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501315"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28706"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00114-9"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-0816"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512610"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3202"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(16)30002-4"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29139"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-1205"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13883"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.039"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01229-15"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.050"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i25.4538"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix260"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315906"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-018-2566-6"},{"issue":"9","key":"e_1_2_9_77_1","first-page":"6","article-title":"New triple therapy for chronic hepatitis C: real life clinical experience in a community setting","volume":"72","author":"Akiyama MJ","year":"2013","journal-title":"Hawaii J Med Public Health"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.03.047"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.09.027"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30496-6"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24971"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704053"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(17)31898-6"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy220"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13132"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix916"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa091"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070666"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.01.011"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01976-13"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.45543"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S127689"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26862-y"},{"key":"e_1_2_9_94_1","unstructured":"Patterns of Resistance\u2010Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct\u2010Acting Antivirals\u2010 ClinicalKey.https:\/\/www.clinicalkey.com\/#!\/content\/playContent\/1-s2.0-S0016508517363539?scrollTo=%23tbl1fnb. Accessed February 20 2020."},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1086\/600893"},{"key":"e_1_2_9_96_1","first-page":"1","article-title":"Baseline quasispecies selection and novel mutations contribute to emerging resistance\u2010associated substitutions in hepatitis C virus after direct\u2010acting antiviral treatment","volume":"2017","author":"Kai Y","year":"2016","journal-title":"Sci Rep"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30225"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.07.038"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.014"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02699.x"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201384j"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12068"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02386-13"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04619-14"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.04024.x"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.12.037"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160668"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04931-y"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.20517\/2394-5079.2017.18"},{"key":"e_1_2_9_110_1","doi-asserted-by":"crossref","first-page":"ofz076","DOI":"10.1093\/ofid\/ofz076","article-title":"Open forum infectious diseases identification of 19 novel hepatitis C virus subtypes\u2010further expanding HCV classification","volume":"6","author":"Hedskog C","year":"2019","journal-title":"Forum Infectious Diseases."}],"container-title":["Reviews in Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Frmv.2120","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.2120","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rmv.2120","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.2120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T07:09:16Z","timestamp":1693897756000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmv.2120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":109,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/rmv.2120"],"URL":"https:\/\/doi.org\/10.1002\/rmv.2120","archive":["Portico"],"relation":{},"ISSN":["1052-9276","1099-1654"],"issn-type":[{"value":"1052-9276","type":"print"},{"value":"1099-1654","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"2020-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2120"}}