{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:40Z","timestamp":1786115620185,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15\u201330% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders.<\/jats:p>","DOI":"10.3390\/cancers18152501","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:08:09Z","timestamp":1785856089000},"page":"2501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Direct-Acting Antivirals (DAAs) in Hepatitis C Virus-Associated Lymphoproliferative Disorders"],"prefix":"10.3390","volume":"18","author":[{"given":"Cesare","family":"Mazzaro","sequence":"first","affiliation":[{"name":"Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8746-9404","authenticated-orcid":false,"given":"Riccardo","family":"Bomben","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-9149","authenticated-orcid":false,"given":"Laura","family":"Gragnani","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Visentini","sequence":"additional","affiliation":[{"name":"Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Translational and Precision Medicine, Sapienza University of Rome,  00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Agostinis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital of Tolmezzo, 33028 Tolmezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6745-8786","authenticated-orcid":false,"given":"Silvia","family":"Marri","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-4166","authenticated-orcid":false,"given":"Anna Linda","family":"Zignego","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter","family":"Gattei","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S2468-1253(25)00375-9","article-title":"The burden of chronic hepatitis B and C in 2022 and progress towards elimination: A global report","volume":"11","author":"Cui","year":"2026","journal-title":"Lancet Gastroenterol. 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