{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:56:51Z","timestamp":1790488611687,"version":"4.1.0"},"reference-count":79,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The long\u2010term effects of direct\u2010acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta\u2010analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non\u2010DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random\u2010effects meta\u2010analyses with inverse variance weighting, with sensitivity analyses and meta\u2010regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI\u00a0=\u00a00.44; 0.38\u20100.52), decompensation (HR; CI\u00a0=\u00a00.54; 0.38\u2010 0.76) and HCC occurrence (HR; CI\u00a0=\u00a00.72; 0.61\u2010 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI\u00a0=\u00a00.72; 0.44\u20101.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI\u00a0=\u00a00.33; 0.23\u20100.46), decompensation (HR; CI\u00a0=\u00a00.11; 0.05\u20100.24), HCC occurrence (HR; CI\u00a0=\u00a00.31; 0.27\u20100.37) and HCC recurrence (HR; CI\u00a0=\u00a00.32; 0.20\u20100.51). Meta\u2010regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow\u2010up. In conclusion, our findings show protective effects of DAA treatment and DAA\u2010related SVR on CHC progression and mortality.<\/jats:p>","DOI":"10.1111\/jvh.13482","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T14:33:06Z","timestamp":1612794786000},"page":"739-754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Impact of direct\u2010acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-064X","authenticated-orcid":false,"given":"Yeva","family":"Sahakyan","sequence":"first","affiliation":[{"name":"Toronto Health Economics and Technology Assessment (THETA) Collaborative Toronto General Hospital Research Institute University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lee\u2010Kim","sequence":"additional","affiliation":[{"name":"Toronto Health Economics and Technology Assessment (THETA) Collaborative Toronto General Hospital Research Institute University Health Network Toronto ON Canada"},{"name":"School of Medicine Queens University Kingston ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Bremner","sequence":"additional","affiliation":[{"name":"Toronto Health Economics and Technology Assessment (THETA) Collaborative Toronto General Hospital Research Institute University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M.","family":"Bielecki","sequence":"additional","affiliation":[{"name":"Toronto Health Economics and Technology Assessment (THETA) Collaborative Toronto General Hospital Research Institute University Health Network Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray D.","family":"Krahn","sequence":"additional","affiliation":[{"name":"Toronto Health Economics and Technology Assessment (THETA) Collaborative Toronto General Hospital Research Institute University Health Network Toronto ON Canada"},{"name":"Institute of Health Policy, Management and Evaluation (IHPME) University of Toronto Toronto ON Canada"},{"name":"Department of Medicine University of Toronto and University Health Network Toronto ON Canada"},{"name":"Institute for Clinical Evaluative Sciences (ICES) Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO.Hepatitis C Fact sheet.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/hepatitis\u2010cAccessed November 09 2020."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22759"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.170453"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27950"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512610"},{"key":"e_1_2_10_7_1","first-page":"CD012143","article-title":"Direct\u2010acting antivirals for chronic hepatitis C","volume":"9","author":"Jakobsen JC","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ396"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.11.018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-5-201303050-00005"},{"key":"e_1_2_10_11_1","volume-title":"Modelling the Incidence and Prevalence of Hepatitis C Infection and Its Sequelae in Canada","author":"Remis RS","year":"2007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.161521"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_2_10_14_1","unstructured":"HigginsJPT ThomasJ ChandlerJ et al.Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). 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