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However, some HCCs may develop in a non-cirrhotic liver, raising uncertainty about their origin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed a prospectively accrued cohort of 2592 CLD patients (median follow-up\u2009=\u200913 years) with no prior evidence of liver cirrhosis. To track the progression of liver fibrosis prior to HCC diagnosis, we examined serial measurements of Fib-4 (an index of liver fibrosis). We also evaluated fibrosis progression in response to antiviral treatment in patients with hepatitis C (HCV) and hepatitis B (HBV). Recognising the limitations of serologic fibrosis assessment, we correlated Fib-4 and fibrosis histology within this cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among HCC patients, 28% had no indication of cirrhosis prior to HCC diagnosis. Only 31% of HBV-related HCC cases followed the cirrhotic pathway. HCV patients who achieved sustained virological response (SVR) developed cirrhosis approximately 7 years before HCC diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis challenges the notion of cirrhosis as an obligatory stage of HCC development in CLD patients. We affirm HBV\u2019s direct oncogenic potential and find that achieving SVR does not universally prevent HCC development. Our findings have major implications for HCC surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s44276-024-00050-0","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T08:02:14Z","timestamp":1714723334000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Progression of chronic liver disease to hepatocellular carcinoma: implications for surveillance and management"],"prefix":"10.1038","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1404-0209","authenticated-orcid":false,"given":"Philip J.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Kalyuzhnyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Boswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"50_CR1","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","volume":"69","author":"European Association for the Study of the Liver.","year":"2018","unstructured":"European Association for the Study of the Liver. 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