{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:17:27Z","timestamp":1779293847243,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Hepatitis C virus (HCV) remains a major cause of preventable liver-related mortality in the United States despite highly effective direct-acting antivirals (DAAs). Contemporary assessment of mortality trends and disparities is essential for elimination efforts. Methods: Using CDC WONDER multiple cause-of-death data (1999\u20132023), we identified HCV-related deaths using ICD-10 codes for acute and chronic HCV (B17.1, B18.2) and calculated age-adjusted mortality rates (AAMRs) per 100,000 (2000 US standard). Rates were stratified by sex, race\/ethnicity, census region, and 2013 NCHS urban\u2013rural classification. Joinpoint regression quantified temporal inflection points and annual percent changes (APCs). Results: Overall HCV-related AAMR increased from 1.8 (1999) to a peak of 5.0 (2014), then declined to 2.3 (2023), with a marked post-2014 decrease (APC \u22128.2%). Mortality was consistently higher in males than females (2023 rate ratio 2.57). In 2023, American Indian\/Alaska Native individuals had the highest mortality (AAMR 8.7; rate ratio 3.48 vs. non-Hispanic White), followed by non-Hispanic Black individuals (AAMR 6.2; rate ratio 2.48). Mortality remained highest in the West and was higher in non-metropolitan than metropolitan counties (AAMR 2.8 vs. 2.3; rate ratio 1.22), with a slower post-2014 decline in non-metropolitan areas. Conclusions: Our findings indicate that while the DAA era has been associated with a substantial reduction in HCV-related mortality at the national level, this progress has not been uniform across all populations. Persistent excess mortality among Native American and non-Hispanic Black individuals may reflect inequities in the HCV care cascade, including screening, confirmatory testing, linkage to specialty care, insurance-related restrictions, and the high cost of antiviral therapy. These results highlight the need for policies and public health strategies that improve equitable and affordable access to curative HCV treatment.<\/jats:p>","DOI":"10.3390\/v18050576","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:34Z","timestamp":1779291934000},"page":"576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Discovery to Cure\u2014Where Are We Now? Mortality Trends in Chronic Hepatitis C: An Analysis of CDC WONDER Database (1999\u20132023)"],"prefix":"10.3390","volume":"18","author":[{"given":"Ashraf","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Guthrie Robert Packer Hospital, Sayre, PA 18840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hina","family":"Wazir","sequence":"additional","affiliation":[{"name":"Jamaica Hospital Medical Center, Richmond Hill, New York City, NY 11418, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4146-7787","authenticated-orcid":false,"given":"Abdullah","family":"Sultany","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Guthrie Robert Packer Hospital, Sayre, PA 18840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalil Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Ibrahim","family":"Sultani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, Ankara 06800, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4842-6368","authenticated-orcid":false,"given":"Naeem Ahmed","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, NYC Health + Hospitals\/Woodhull, Brooklyn, NY 11206, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Ghurki Trust Teaching Hospital, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mati Ullah Dad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Oklahoma, Norman, OK 73019, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amlish","family":"Gondal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Guthrie Robert Packer Hospital, Sayre, PA 18840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). Global Progress Report on HIV, Viral Hepatitis and Sexually Transmitted Infections, 2021, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/hep.30297","article-title":"Estimating prevalence of hepatitis C virus infection in the United States, 2013\u20132016","volume":"69","author":"Hofmeister","year":"2019","journal-title":"Hepatology"},{"key":"ref_3","first-page":"1","article-title":"Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945\u20131965","volume":"61","author":"Smith","year":"2012","journal-title":"MMWR Recomm. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/cid\/ciw111","article-title":"Rising mortality associated with hepatitis C virus in the United States, 2003\u20132013","volume":"62","author":"Ly","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hall, E.W., Rosenberg, E.S., and Sullivan, P.S. (2018). Estimates of state-level chronic hepatitis C virus infection stratified by race and sex, United States, 2010. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3133-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.dld.2010.05.006","article-title":"Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States","volume":"43","author":"Rein","year":"2011","journal-title":"Dig. Liver Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"461","DOI":"10.15585\/mmwr.mm6518a2","article-title":"Identification and clinical management of persons with chronic hepatitis C virus infection\u2014Cherokee Nation, 2012\u20132015","volume":"65","author":"Mera","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/hep.22375","article-title":"Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis","volume":"48","author":"Thein","year":"2008","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1056\/NEJMoa1012912","article-title":"Telaprevir for previously untreated chronic hepatitis C virus infection","volume":"364","author":"Jacobson","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1056\/NEJMoa1402454","article-title":"Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection","volume":"370","author":"Afdhal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1056\/NEJMoa1402355","article-title":"Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis","volume":"370","author":"Kowdley","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1001\/jama.2014.7085","article-title":"Treatment of hepatitis C: A systematic review","volume":"312","author":"Kohli","year":"2014","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/hep.28625","article-title":"Real-world effectiveness of ledipasvir\/sofosbuvir in 4,365 treatment-naive, genotype 1 HCV-infected patients","volume":"64","author":"Backus","year":"2016","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(18)32111-1","article-title":"Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: A prospective cohort study","volume":"393","author":"Carrat","year":"2019","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.21037\/tgh.2019.03.04","article-title":"Liver-related mortality in the United States: Hepatitis C declines, NAFLD and alcohol rise","volume":"4","author":"Lee","year":"2019","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/hep.30161","article-title":"Changing trends in etiology-based and ethnicity-based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States","volume":"69","author":"Kim","year":"2019","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/jvh.13218","article-title":"Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment","volume":"27","author":"Daniel","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/apt.15291","article-title":"The impact of direct-acting antivirals on the hepatitis C care cascade","volume":"50","author":"Chhatwal","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/jvh.12506","article-title":"Disparate access to treatment regimens in chronic hepatitis C patients: Data from the TRIO network","volume":"23","author":"Younossi","year":"2016","journal-title":"J. Viral Hepat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/0033354919887748","article-title":"Hepatitis C\u2013related mortality among American Indian\/Alaska Native persons in the Northwestern United States, 2006\u20132012","volume":"135","author":"Hatcher","year":"2020","journal-title":"Public Health Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"775","DOI":"10.7326\/M16-2350","article-title":"Hepatitis C virus infection among reproductive-aged women and children in the United States, 2006\u20132014","volume":"166","author":"Ly","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_22","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":"Alzahrani","year":"2020","journal-title":"J. Gastroenterol. Hepatol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/apt.12200","article-title":"Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: Results from a US database of over 45,000 HCV-infected, evaluated patients","volume":"37","author":"Talal","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_24","first-page":"86","article-title":"Hepatitis C treatment at a rural Navajo health clinic using Project ECHO","volume":"20","author":"Nance","year":"2020","journal-title":"Online J. Rural. Nurs. Health Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1093\/cid\/ciz976","article-title":"Deaths associated with hepatitis C virus infection among residents in 50 states and DC, 2016\u20132017","volume":"71","author":"Ly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2105\/AJPH.2017.304132","article-title":"Increases in acute hepatitis C virus infection related to the opioid epidemic, United States, 2004\u20132014","volume":"108","author":"Zibbell","year":"2018","journal-title":"Am. J. Public Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/cid\/ciu643","article-title":"Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs","volume":"59","author":"Suryaprasad","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/hep.31756","article-title":"County-level variation in hepatitis C virus mortality and trends in the United States, 2005\u20132017","volume":"74","author":"Hall","year":"2021","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70011","DOI":"10.1111\/jvh.70011","article-title":"Enhancing hepatitis C management: Mortality trends and disparities in the US by sex, age group, race\/ethnicity and region (1999\u20132020)","volume":"32","author":"Ahmed","year":"2025","journal-title":"J. Viral Hepat."},{"key":"ref_30","unstructured":"U.S. Department of Health and Human Services (2020). Viral Hepatitis National Strategic Plan for the United States: A Roadmap to Elimination (2021\u20132025)."},{"key":"ref_31","unstructured":"Centers for Disease Control and Prevention (2023). CDC WONDER: Underlying Cause of Death, 1999\u20132023."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1007\/s10620-025-09161-1","article-title":"Trends in Mortality Caused by Hepatitis C Virus in the United States Population: A Retrospective Cross-Sectional Study Using the CDC WONDER Database","volume":"70","author":"Ekpendu","year":"2025","journal-title":"Dig. Dis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106940","DOI":"10.4254\/wjh.v17.i5.106940","article-title":"Trends in viral hepatitis\u2013related mortality in the United States from 1999 to 2022: A retrospective study","volume":"17","author":"Ahlers","year":"2025","journal-title":"World J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/jvh.13436","article-title":"Hepatitis C virus infection mortality trends according to three definitions with special concern for the baby boomer birth cohort","volume":"28","author":"Sheu","year":"2021","journal-title":"J. Viral Hepat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/cid\/ciu077","article-title":"Mortality among persons in care with hepatitis C virus infection","volume":"58","author":"Mahajan","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","unstructured":"Ingram, D.D., and Franco, S.J. (2014). 2013 NCHS Urban-Rural Classification Scheme for Counties."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Klein, R.J., and Schoenborn, C.A. (2001). Age Adjustment Using the 2000 Projected U.S. Population.","DOI":"10.1037\/e583772012-001"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/(SICI)1097-0258(20000215)19:3<335::AID-SIM336>3.0.CO;2-Z","article-title":"Permutation tests for joinpoint regression","volume":"19","author":"Kim","year":"2000","journal-title":"Stat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1002\/sim.3733","article-title":"Estimating average annual percent change in trend analysis","volume":"28","author":"Clegg","year":"2009","journal-title":"Stat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2011055","DOI":"10.1001\/jamanetworkopen.2020.11055","article-title":"Association of DAA treatment with mortality among Medicare beneficiaries with hepatitis C","volume":"3","author":"Kalidindi","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/cid\/civ894","article-title":"The impact of enhanced screening and treatment on hepatitis C in the United States","volume":"62","author":"Durham","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(17)30569-X","article-title":"Structural racism and health inequities in the USA","volume":"389","author":"Bailey","year":"2017","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jama.2016.7186","article-title":"The need to expand access to hepatitis C virus drugs in the Indian Health Service","volume":"316","author":"Leston","year":"2016","journal-title":"JAMA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/jrh.12733","article-title":"Evaluation of treatment access and scope of a multistate hepatitis C virus Extension for Community Healthcare Outcomes telehealth service in the US Indian Health System, 2017\u20132021","volume":"39","author":"Wirth","year":"2023","journal-title":"J. Rural. Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1056\/NEJMoa1009370","article-title":"Outcomes of treatment for hepatitis C virus infection by primary care providers","volume":"364","author":"Arora","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.7326\/M15-0406","article-title":"Restrictions for Medicaid reimbursement of sofosbuvir","volume":"163","author":"Barua","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S2468-1253(17)30404-1","article-title":"Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): An open-label, single-arm, phase 4, multicentre trial","volume":"3","author":"Grebely","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/jvh.70087","article-title":"HCV testing and treatment of adults in the United States: 2014\u20132021","volume":"32","author":"Ghany","year":"2025","journal-title":"J. Viral Hepat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.amepre.2021.03.011","article-title":"Decreases in hepatitis C testing and treatment during the COVID-19 pandemic","volume":"61","author":"Kaufman","year":"2021","journal-title":"Am. J. Prev. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Casey, E., Gala, K., Cohen, G., LeLaurin, M., Dai, X., and Kaplan-Lewis, E. (2025). The Utilization and Impact of Interconnected Electronic Health Record Tools on Hepatitis C Elimination Efforts in a Large Municipal Healthcare System. Viruses, 17.","DOI":"10.3390\/v17101297"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/576\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:47:53Z","timestamp":1779292073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["v18050576"],"URL":"https:\/\/doi.org\/10.3390\/v18050576","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}