{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:28:10Z","timestamp":1793327290092,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"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>Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management, offering high cure rates, favorable safety, and simplified regimens. Management in immunosuppressed patients remains challenging due to drug\u2013drug interactions (DDIs). The objective of this review is to summarize clinical outcomes, safety, and pharmacologic considerations of DAA therapy in immunosuppressed patients, including solid organ transplant recipients and those on biological agents. We reviewed clinical studies, pharmacologic databases, and guidelines to characterize DAA classes, mechanisms, and relevant DDIs in immunosuppressed HCV patients. In transplant recipients, DAAs achieved sustained virological response (SVR) &gt; 90% with minimal graft rejection. Safety profiles were favorable, and immunosuppressant dose adjustments were rarely needed. DDIs, particularly with calcineurin inhibitors (tacrolimus, cyclosporine), require careful monitoring due to variable trough-level effects. Evidence also supports the efficacy and safety of DAAs in patients on biological agents, without compromising SVR. Pharmacokinetic data indicate DAAs maintain antiviral activity across HCV genotypes in the presence of immunosuppressants, though mTOR inhibitors may alter efficacy in certain HCV genotypes. DAAs are highly effective and safe in immunosuppressed patients, achieving high SVR rates and potential graft survival benefits. Prospective studies are needed to assess DAA therapy in patients receiving biological agents and to optimize co-administration strategies with immunosuppressive agents.<\/jats:p>","DOI":"10.3390\/v17111422","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:50:48Z","timestamp":1761533448000},"page":"1422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatitis C Direct-Acting Antivirals in the Immunosuppressed Host: Mechanisms, Interactions, and Clinical Outcomes"],"prefix":"10.3390","volume":"17","author":[{"given":"Hoor","family":"AlKaabi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Internal Medicine, The Medical City for Military and Security Services, Muscat 111, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham","family":"AlSinani","sequence":"additional","affiliation":[{"name":"Department of Child Health, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman"},{"name":"Department of Child Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-6894","authenticated-orcid":false,"given":"Mohamed","family":"El-Kassas","sequence":"additional","affiliation":[{"name":"Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo11795, Egypt"},{"name":"Applied Science Research Center, Applied Science Private University, Amman 11931, Jordan"},{"name":"Steatotic Liver Diseases Study Foundation in the Middle East and North Africa (SLMENA), Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid A.","family":"Alswat","sequence":"additional","affiliation":[{"name":"Steatotic Liver Diseases Study Foundation in the Middle East and North Africa (SLMENA), Cairo 11795, Egypt"},{"name":"Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-266X","authenticated-orcid":false,"given":"Khalid M.","family":"AlNaamani","sequence":"additional","affiliation":[{"name":"Steatotic Liver Diseases Study Foundation in the Middle East and North Africa (SLMENA), Cairo 11795, Egypt"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, The Medical City for Military and Security Services, Muscat 111, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yang, J., Qi, J.L., Wang, X.X., Li, H.H., Jin, R., Liu, B.Y., Liu, H.X., and Rao, H.Y. 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