{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:32:46Z","timestamp":1788535966150,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"am","delay-in-days":344,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000936","name":"Gordon and Betty Moore Foundation","doi-asserted-by":"publisher","award":["Grant No. 2919.01"],"award-info":[{"award-number":["Grant No. 2919.01"]}],"id":[{"id":"10.13039\/100000936","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000076","name":"Directorate for Biological Sciences","doi-asserted-by":"publisher","award":["PHY11\u201025915"],"award-info":[{"award-number":["PHY11\u201025915"]}],"id":[{"id":"10.13039\/100000076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["NIH grants R25GM067110, R01AI028433, R01OD011095,"],"award-info":[{"award-number":["NIH grants R25GM067110, R01AI028433, R01OD011095,"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The decay rate of hepatitis C virus (HCV)\u2010infected cells during therapy has been used to determine the duration of treatment needed to attain a sustained virologic response, but with direct\u2010acting anti\u2010virals (DAA), this rate has been difficult to estimate. Here, we show that it is possible to estimate it, by simultaneously analysing the viral load and alanine aminotransferase (ALT) kinetics during combination DAA therapy. We modelled the HCV RNA and ALT serum kinetics in 26 patients with chronic HCV genotype 1b infection, under four different sofosbuvir\u2010based combination treatments. In all patients, ALT decayed exponentially to a set point in the normal range by 1\u20103\u00a0weeks after initiation of therapy. The model indicates that the ALT decay rate during the first few weeks after initiation of therapy reflects the death rate of infected cells, with an estimated median half\u2010life of 2.5\u00a0days in this patient population. This information allows independent estimation of the rate of loss of intracellular replication complexes during therapy. Our model also predicts that the final ALT set point is not related to the release of ALT by dying HCV\u2010infected cells. Using ALT data, one can separately obtain information about the rate of \u2018cure\u2019 of HCV\u2010infected cells versus their rate of death, something not possible when analysing only HCV RNA data. This information can be used to compare the effects of different DAA combinations and to rationally evaluate their anti\u2010viral effects.<\/jats:p>","DOI":"10.1111\/jvh.13229","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T09:09:22Z","timestamp":1572512962000},"page":"261-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Disentangling the lifespans of hepatitis C virus\u2010infected cells and intracellular vRNA replication\u2010complexes during direct\u2010acting anti\u2010viral therapy"],"prefix":"10.1111","volume":"27","author":[{"given":"Erwing Fabian","family":"Cardozo","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Ji","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center of Chinese PLA General Hospital (302 Hospital)\u2010Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-3769","authenticated-orcid":false,"given":"George","family":"Lau","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center of Chinese PLA General Hospital (302 Hospital)\u2010Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre Beijing China"},{"name":"Humanity and Health Clinical Trial Center Humanity &amp; Health Medical Group Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Center for AIDS Research Emory University School of Medicine Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010feng","family":"Chen","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center of Chinese PLA General Hospital (302 Hospital)\u2010Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruy M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics Group Los Alamos National Laboratory Los Alamos NM USA"},{"name":"Laborat\u00f3rio de Biomatem\u00e1tica Faculdade de Medicina da Universidade de Lisboa Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics Group Los Alamos National Laboratory Los Alamos NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-016-9717-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.026"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy585"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(16)30015-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22109"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1991.00400020036008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50344"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203110110"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002959"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2013.04.012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1201\/b17203","volume-title":"Mixed Effects Models for the Population Approach: Models, Tasks, Methods and Tools","author":"Lavielle M","year":"2014"},{"key":"e_1_2_9_13_1","first-page":"488","volume-title":"Selection and Multimodel Inference: a Practical Information\u2010Theoretic Approach","author":"Burnham KP","year":"2003"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.11.001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520802044210"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177352"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5386.103"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03153"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.35"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir835"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04079"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3447"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.043"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12702"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13594-13605.2005"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13229","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/jvh.13229","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T05:17:34Z","timestamp":1694063854000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,22]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1111\/jvh.13229"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13229","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,22]]},"assertion":[{"value":"2019-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}