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It primarily targets the liver but also causes systemic complications through inflammation, oxidative stress, and metabolic dysregulation. HCV is a highly variable RNA virus with six major genotypes that are mainly transmitted via blood. Often asymptomatic, the infection progresses silently to chronic hepatitis C (CHC), which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have revolutionized treatment, achieving cure rates above 95%, improving liver function, reversing fibrosis, and normalizing metabolism. HCV disrupts iron metabolism by suppressing hepcidin, causing iron overload and oxidative stress. It also alters lipid metabolism, inducing steatosis, and affects glucose metabolism, contributing to insulin resistance and type 2 diabetes. DAAs improve these metabolic outcomes. HCV promotes oxidative stress via viral proteins, damaging liver cells and DNA and triggering inflammation and fibrogenesis. Even post-cure, oxidative stress and iron overload may continue to drive disease progression. Genetic and epigenetic factors influence fibrosis progression and HCC risk. Despite a sustained virologic response (SVR), patients with advanced liver damage remain at risk for HCC and metabolic diseases, highlighting the need for continued monitoring and personalized post-treatment care.<\/jats:p>","DOI":"10.3390\/ijms27083559","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:05:36Z","timestamp":1776348336000},"page":"3559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatitis C Virus: An Overview of Its Chronic Impact on Liver Function, Metabolic Dysregulation, Inflammatory\u2013Oxidative Pathogenesis and Epigenetic Memory"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-3274","authenticated-orcid":false,"given":"Joana","family":"Ferreira","sequence":"first","affiliation":[{"name":"Institute for Scientific Research Bento Rocha Cabral, 1250-047 Lisbon, Portugal"},{"name":"Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1600-190 Lisbon, Portugal"},{"name":"Environmental Health Institute (ISAMB), Lisbon Medical School, University of Lisbon, Associated Laboratory TERRA, Higher Institute of Agronomy, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3353-9470","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Caldeira","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1600-190 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-5687","authenticated-orcid":false,"given":"Manuel","family":"Bicho","sequence":"additional","affiliation":[{"name":"Institute for Scientific Research Bento Rocha Cabral, 1250-047 Lisbon, Portugal"},{"name":"Environmental Health Institute (ISAMB), Lisbon Medical School, University of Lisbon, Associated Laboratory TERRA, Higher Institute of Agronomy, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-4867","authenticated-orcid":false,"given":"Paula","family":"Faustino","sequence":"additional","affiliation":[{"name":"Environmental Health Institute (ISAMB), Lisbon Medical School, University of Lisbon, Associated Laboratory TERRA, Higher Institute of Agronomy, 1649-028 Lisbon, Portugal"},{"name":"Human Genetics Department, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Serejo","sequence":"additional","affiliation":[{"name":"Environmental Health Institute (ISAMB), Lisbon Medical School, University of Lisbon, Associated Laboratory TERRA, Higher Institute of Agronomy, 1649-028 Lisbon, Portugal"},{"name":"Gastroenterology and Hepatology Department, Hospital de Santa Maria, 1649-028 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, July 25). 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