{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:57:16Z","timestamp":1792155436243,"version":"4.4.0"},"reference-count":33,"publisher":"The Korean Association for the Study of the Liver","issue":"4","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["031L0294C"],"award-info":[{"award-number":["031L0294C"]}]},{"name":"German Federal Ministry of Education and Research","award":["031L0294A"],"award-info":[{"award-number":["031L0294A"]}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","award":["TTU 05.708_00"],"award-info":[{"award-number":["TTU 05.708_00"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","award":["TTU-IICH-07-808"],"award-info":[{"award-number":["TTU-IICH-07-808"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390874280"],"award-info":[{"award-number":["390874280"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2020_ EKPK.20"],"award-info":[{"award-number":["2020_ EKPK.20"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:p>Background\/Aims: Hepatitis C virus (HCV) infection remains a global health challenge, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Despite the high efficacy of direct-acting antiviral therapy in achieving sustained virologic response (SVR), concerns persist regarding long-term immune alterations and residual risks, particularly in cirrhotic patients.Methods: This study investigates 75 soluble immune mediator (SIM) profiles in 102 chronic HCV patients, stratified by cirrhosis status, at therapy initiation, end of treatment, and long-term follow-up (median 96 weeks). Findings were compared with 51 matched healthy controls and validated in an independent cohort of 47 cirrhotic patients, 17 of whom developed HCC.Results: We observed significant SIM alterations at baseline, with cirrhotic patients displaying a more profoundly dysregulated inflammatory milieu. Despite an overall decline in inflammatory markers following SVR, persistent alterations were evident, particularly in cirrhotic patients. Notably, those with liver stiffness exceeding 14 kPa exhibited sustained inflammatory dysregulation, correlating with liver elastography values. Key SIM such as interleukin (IL)-6, IL-8, urokinase plasminogen activator, and hepatocellular growth factor remained elevated and were associated with HCC development. Network analysis highlighted their roles in liver fibrosis, regeneration, and carcinogenesis.Conclusions: These findings underscore the importance of early antiviral intervention to prevent cirrhosis-related sequelae. Future studies should explore the mechanistic pathways linking chronic inflammation, fibrosis, and oncogenesis to identify predictive biomarkers and novel therapeutic targets. Addressing persistent immune alterations post-HCV clearance may improve long-term outcomes, particularly in patients with advanced liver disease.<\/jats:p>","DOI":"10.3350\/cmh.2025.0292","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T03:42:15Z","timestamp":1749008535000},"page":"1269-1284","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Distinct inflammatory imprint in non-cirrhotic and cirrhotic patients before and after direct-acting antiviral therapy"],"prefix":"10.3350","volume":"31","author":[{"given":"Moana","family":"Witte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Oltmanns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tauwaldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Schmaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Mischke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Grabert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Bretthauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart M.","family":"Roesner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Werfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Deterding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Maasoumy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Kacprowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke R.M.","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-8001","authenticated-orcid":true,"given":"Markus","family":"Cornberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","volume-title":""},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00759-2"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2033539"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32341"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.11.040"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01845-5"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1177\/13596535211072672"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102324"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04685-9"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.02.038"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1177\/2050640620976991"},{"key":"ref12","first-page":"472","volume-title":"Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment","author":"Du","year":"2022"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.035"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab048"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw457"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11061529"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00811.x"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01299-6"},{"key":"ref19","volume-title":""},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27971"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01388-08"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.02007-13"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.02.006"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/cells7110196"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1097\/qad.0000000000000654"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.10.035"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0342-4"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05289-6"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30774"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.02.004"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.787748"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00055"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.3390\/v14081613","volume-title":"The effect of treatment-induced viral eradication on cytokine and growth factor expression in chronic hepatitis C","author":"Radmani\u0107","year":"2022"}],"container-title":["Clinical and Molecular Hepatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-cmh.org\/upload\/pdf\/cmh-2025-0292.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cmh.org\/journal\/view.php?doi=10.3350\/cmh.2025.0292","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cmh.org\/upload\/pdf\/cmh-2025-0292.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:50:28Z","timestamp":1760601028000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-cmh.org\/journal\/view.php?doi=10.3350\/cmh.2025.0292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"URL":"https:\/\/doi.org\/10.3350\/cmh.2025.0292","relation":{},"ISSN":["2287-2728","2287-285X"],"issn-type":[{"value":"2287-2728","type":"print"},{"value":"2287-285X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}