{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:31:12Z","timestamp":1771273872416,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veneto region","award":["D.G.R. N\u00b0791\/2018"],"award-info":[{"award-number":["D.G.R. N\u00b0791\/2018"]}]},{"name":"Veneto region","award":["DOR 2021 N\u00b021-47470"],"award-info":[{"award-number":["DOR 2021 N\u00b021-47470"]}]},{"name":"Veneto region","award":["DOR 2024 N\u00b000743"],"award-info":[{"award-number":["DOR 2024 N\u00b000743"]}]},{"name":"Department of Medicine-DIMED","award":["D.G.R. N\u00b0791\/2018"],"award-info":[{"award-number":["D.G.R. N\u00b0791\/2018"]}]},{"name":"Department of Medicine-DIMED","award":["DOR 2021 N\u00b021-47470"],"award-info":[{"award-number":["DOR 2021 N\u00b021-47470"]}]},{"name":"Department of Medicine-DIMED","award":["DOR 2024 N\u00b000743"],"award-info":[{"award-number":["DOR 2024 N\u00b000743"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases. Aims: We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years. Methods: In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset. Results: Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or\/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient\u2019s risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU). Conclusions: Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (&gt;25 kPa), showed the lowest reduction of NIT scores, and developed events in 80\/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score \u2265 8 demonstrated a significant incidence of HCC (37\/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU.<\/jats:p>","DOI":"10.3390\/cancers17091528","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T05:10:32Z","timestamp":1746076232000},"page":"1528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long-Term Risk of Hepatic and Extrahepatic-Related Events After Direct Antiviral Therapy for Chronic Hepatitis C: A Prospective Long-Term Study Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-279X","authenticated-orcid":false,"given":"Luisa","family":"Cavalletto","sequence":"first","affiliation":[{"name":"UOC Clinica Medica 5, Regional Center for Liver Disease Outpatient Unit, Department of Medicine\u2014DIMED, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Bertoli","sequence":"additional","affiliation":[{"name":"Unit of Emergency Medicine, Department of Systems Medicine\u2014DIDAS, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Mescoli","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Medicine\u2014DIMED, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camillo","family":"Aliberti","sequence":"additional","affiliation":[{"name":"Unit of Radiology, Pederzoli Hospital Peschiera del Garda, 37019 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-1488","authenticated-orcid":false,"given":"Maria Giovanna","family":"Quaranta","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Global Health Center, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-224X","authenticated-orcid":false,"given":"Loreta","family":"Kondili","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Global Health Center, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6584-4157","authenticated-orcid":false,"given":"Liliana","family":"Chemello","sequence":"additional","affiliation":[{"name":"UOC Clinica Medica 5, Regional Center for Liver Disease Outpatient Unit, Department of Medicine\u2014DIMED, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6380","DOI":"10.3748\/wjg.v28.i45.6380","article-title":"Best therapy for the easiest to treat hepatitis C virus genotype 1b-infected patients","volume":"28","author":"Jaroszewicz","year":"2022","journal-title":"World J. 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