{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:07:03Z","timestamp":1793387223524,"version":"4.5.0"},"reference-count":96,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery.<\/jats:p>","DOI":"10.3390\/diseases13120393","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chronic Hepatitis C in the Direct-Acting Antivirals Era: Carcinogenesis and Clinical Implications"],"prefix":"10.3390","volume":"13","author":[{"given":"Yucel","family":"Aydin","sequence":"first","affiliation":[{"name":"Section of Gastroenterology, Department of Internal Medicine, School of Medicine, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Kurt","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Department of Internal Medicine, School of Medicine, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-9359","authenticated-orcid":false,"given":"Veysel","family":"Tahan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebubekir","family":"Daglilar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41575-020-0332-6","article-title":"Progress towards elimination goals for viral hepatitis","volume":"17","author":"Cox","year":"2020","journal-title":"Nat. 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