{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T03:28:44Z","timestamp":1769743724947,"version":"3.49.0"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Hepatitis C virus (HCV) has high global prevalence and can lead to liver complications and death. Access to direct-acting antivirals (DAAs) in Canada increased following several policy changes, however the real-world impact of expanded DAA access and increased use of these drugs is unknown.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>We aimed to determine the early change in rates of HCV-related hospitalizations overall and HCV-related hospitalizations with hepatocellular carcinoma (HCC) after expanded DAA access.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a population-based time series analysis using national administrative health databases in Canada. Rates of HCV-related hospitalizations and HCV-related hospitalizations with HCC were enumerated monthly between April 2006 and March 2020. We used Autoregressive Integrated Moving Average (ARIMA) models with ramp functions in October 2014 and January 2017 to evaluate the impact of policies to expand DAA access on hospitalization outcomes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Rates of HCV-related hospitalizations in Canada increased between 2006 and 2014, and gradually declined thereafter. The decrease after October 2014, or the first policy change, was significant (p = 0.0355), but no further change was found after the second policy change in 2017 (p = 0.2567). HCV-related hospitalizations with HCC increased until end of 2013, followed by a plateau, before declining in 2016. No significant shifts were found after the first policy change in 2014 (p = 0.1291) nor the second policy change in 2017 (p = 0.6324). Subgroup analyses revealed that those aged 50\u201364 and males had observable declines in rates of HCV-related hospitalizations in the year prior to the first policy change.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Expanding DAA access was associated with a drop in HCV-related hospitalizations in the overall Canadian population coinciding with the 2014 policy change. In light of the time required for HCV-related complications to manifest, continued ongoing research examining the real-world effectiveness of DAAs is required.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0284914","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T17:27:12Z","timestamp":1691515632000},"page":"e0284914","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["The impact of expanded access to direct acting antivirals for Hepatitis C virus on patient outcomes in Canada"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4072-0083","authenticated-orcid":true,"given":"Cherry","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Antoniou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-0052","authenticated-orcid":true,"given":"William W. L.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Janjua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-5307","authenticated-orcid":true,"given":"Jason Robert","family":"Guertin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin L.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Feld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1911-6129","authenticated-orcid":true,"given":"Mina","family":"Tadrous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"pone.0284914.ref001","author":"World Health Organization","year":"2021","journal-title":"Hepatitis C"},{"key":"pone.0284914.ref002","article-title":"Hepatitis C virus infection in liver transplant candidates and recipients2022 April 20, 2022","author":"EC Verna"},{"issue":"2","key":"pone.0284914.ref003","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s40471-017-0108-x","article-title":"Hepatitis C: Review of the Epidemiology, Clinical Care, and Continued Challenges in the Direct Acting Antiviral Era","volume":"4","author":"AJ Millman","year":"2017","journal-title":"Curr Epidemiol Rep"},{"key":"pone.0284914.ref004","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2147\/IJGM.S127689","article-title":"Hepatitis C treatment: where are we now?","volume":"10","author":"NJ Burstow","year":"2017","journal-title":"Int J Gen Med"},{"issue":"4","key":"pone.0284914.ref005","doi-asserted-by":"crossref","first-page":"ofaa095","DOI":"10.1093\/ofid\/ofaa095","article-title":"Re-treatment of Hepatitis C Infection After Multiple Failures of Direct-Acting Antiviral Therapy","volume":"7","author":"DS Fierer","year":"2020","journal-title":"Open Forum Infect Dis"},{"issue":"7","key":"pone.0284914.ref006","doi-asserted-by":"crossref","first-page":"e2011055","DOI":"10.1001\/jamanetworkopen.2020.11055","article-title":"Association of Direct-Acting Antiviral Treatment With Mortality Among Medicare Beneficiaries With Hepatitis C","volume":"3","author":"Y Kalidindi","year":"2020","journal-title":"JAMA Network Open"},{"issue":"1","key":"pone.0284914.ref007","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13027-016-0071-z","article-title":"Price and affordability of direct-acting antiviral regimens for hepatitis C virus in the United States","volume":"11","author":"ES Rosenthal","year":"2016","journal-title":"Infectious Agents and Cancer"},{"issue":"4","key":"pone.0284914.ref008","doi-asserted-by":"crossref","first-page":"E605","DOI":"10.9778\/cmajo.20160008","article-title":"Restrictions for reimbursement of direct-acting antiviral treatment for hepatitis C virus infection in Canada: a descriptive study","volume":"4","author":"AD Marshall","year":"2016","journal-title":"CMAJ Open"},{"key":"pone.0284914.ref009","unstructured":"Gilead Sciences Inc. Health Canada issues notice of compliance for Gilead\u2019s Harvoni\u2122 (ledipasvir\/sofosbuvir), the first once-daily single tablet regimen for the treatment of genotype 1 chronic hepatitis C: Cision,; 2014 [cited 2022 December 13]. Available from: https:\/\/www.newswire.ca\/news-releases\/health-canada-issues-notice-of-compliance-for-gileads-harvoni-ledipasvirsofosbuvir-the-first-once-daily-single-tablet-regimen-for-the-treatment-of-genotype-1-chronic-hepatitis-c-515909211.html."},{"key":"pone.0284914.ref010","first-page":"e20200025","article-title":"Prescribing trends in direct-acting antivirals for the treatment of hepatitis C in Ontario, Canada.","volume":"4","author":"M Tadrous","year":"2020","journal-title":"Canadian Liver Journal"},{"key":"pone.0284914.ref011","doi-asserted-by":"crossref","first-page":"e20200041","DOI":"10.3138\/canlivj-2020-0041","article-title":"Comparison of public and private payments for direct-acting antivirals (DAAs) across Canada","volume":"4","author":"A Shakeri","year":"2021","journal-title":"Canadian Liver Journal"},{"issue":"7\u20138","key":"pone.0284914.ref012","doi-asserted-by":"crossref","first-page":"150","DOI":"10.14745\/ccdr.v44i78a01","article-title":"Impact of availability of direct-acting antivirals for hepatitis C on Canadian hospitalization rates, 2012\u20132016","volume":"44","author":"D Schanzer","year":"2018","journal-title":"Can Commun Dis Rep"},{"issue":"6","key":"pone.0284914.ref013","first-page":"30","article-title":"Hospitalization related to chronic hepatitis B and C in recent immigrants in Canada: An immigration administrative data-linked, population-based cohort study.","volume":"33","author":"E Ng","year":"2022","journal-title":"Health Rep"},{"key":"pone.0284914.ref014","unstructured":"Statistics Canada. Population estimates, quarterly 2022 [cited 2023 February 17]. Available from: https:\/\/www150.statcan.gc.ca\/t1\/tbl1\/en\/tv.action?pid=1710000901."},{"key":"pone.0284914.ref015","first-page":"181","article-title":"The impact of new DAA therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection in Ontario: A model-based analysis.","volume":"5","author":"F Forouzannia","year":"2022","journal-title":"Canadian Liver Journal"},{"key":"pone.0284914.ref016","article-title":"Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C.","author":"E Ogawa","year":"2022","journal-title":"JAMA Internal Medicine"},{"issue":"11","key":"pone.0284914.ref017","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1097\/MEG.0000000000001195","article-title":"Treatment of hepatitis C with direct-acting antivirals significantly reduces liver-related hospitalizations in patients with cirrhosis","volume":"30","author":"LA Hill","year":"2018","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"6","key":"pone.0284914.ref018","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.jhep.2020.07.018","article-title":"Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions by 2025","volume":"73","author":"S Rodr\u00edguez-Tajes","year":"2020","journal-title":"Journal of Hepatology"},{"issue":"8","key":"pone.0284914.ref019","first-page":"1453","article-title":"Lower Rates of Emergency Department Visits and Hospitalizations Among Patients With Chronic Hepatitis C With Sustained Virological Response to Interferon-Free Direct-Acting Antiviral Therapy (2014\u20132018) Clinical Infectious Diseases","volume":"75","author":"SC Gordon","year":"2022"},{"issue":"8","key":"pone.0284914.ref020","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/jvh.12684","article-title":"Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study","volume":"24","author":"NZ Janjua","year":"2017","journal-title":"Journal of Viral Hepatitis"},{"issue":"2","key":"pone.0284914.ref021","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jhep.2019.04.014","article-title":"Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia","volume":"71","author":"M Alavi","year":"2019","journal-title":"Journal of Hepatology"},{"issue":"3","key":"pone.0284914.ref022","first-page":"3169","article-title":"Patterns of Hepatitis C-Related Inpatient Mortality in the United States in the Era of Direct-Acting Antivirals","volume":"9","author":"MS Alzahrani","year":"2020","journal-title":"J Gastroenterol Hepatol Res"},{"issue":"8","key":"pone.0284914.ref023","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.7326\/M21-3846","article-title":"Impact of Hepatitis C Treatment Uptake on Cirrhosis and Mortality in Persons Who Inject Drugs","volume":"175","author":"JA Cepeda","year":"2022","journal-title":"Annals of Internal Medicine"},{"key":"pone.0284914.ref024","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jpeds.2017.09.016","article-title":"Increasing Prevalence of Hepatitis C among Hospitalized Children Is Associated with an Increase in Substance Abuse.","volume":"192","author":"AS Barritt","year":"2018","journal-title":"The Journal of Pediatrics"},{"issue":"8","key":"pone.0284914.ref025","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/apt.14271","article-title":"Systematic review: cost-effectiveness of direct-acting antivirals for treatment of hepatitis C genotypes 2\u20136.","volume":"46","author":"T He","year":"2017","journal-title":"Alimentary Pharmacology & Therapeutics"},{"issue":"2","key":"pone.0284914.ref026","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/cid\/civ220","article-title":"The Cost-effectiveness, Health Benefits, and Financial Costs of New Antiviral Treatments for Hepatitis C Virus","volume":"61","author":"DB Rein","year":"2015","journal-title":"Clinical Infectious Diseases"},{"issue":"5","key":"pone.0284914.ref027","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/hep.32237","article-title":"Favorable impact in hepatitis C-related mortality following free access to direct-acting antivirals in Spain","volume":"75","author":"J Politi","year":"2022","journal-title":"Hepatology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284914","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T17:27:40Z","timestamp":1691515660000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284914"}},"subtitle":[],"editor":[{"given":"Yury E.","family":"Khudyakov","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0284914","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}