{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T10:49:29Z","timestamp":1792838969511,"version":"4.5.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen\u2010based contraception discontinuation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen\u2010based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen\u2010based contraception for a median of 12\u2009years. Thirty percent of patients had at least one <jats:italic toggle=\"yes\">HNF1A<\/jats:italic>\u2010inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of \u03b2\u2010catenin (bHCA). Twenty\u2010one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages\u2009&lt;\u200937\u2009years old (<jats:italic toggle=\"yes\">p<\/jats:italic> =\u20090.004) and HCA\u2009&gt;\u20095\u2009cm at imaging were independently associated with symptomatic bleeding (<jats:italic toggle=\"yes\">p<\/jats:italic> =\u20090.003), whereas a bHCA was associated with malignant transformation (<jats:italic toggle=\"yes\">p<\/jats:italic> &lt;\u20090.001). After a median follow\u2010up of 5\u2009years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression (<jats:italic toggle=\"yes\">p<\/jats:italic> &lt;\u20090.0001) and weight gain with progression (<jats:italic toggle=\"yes\">p<\/jats:italic> =\u20090.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29\u20134.19; <jats:italic toggle=\"yes\">p<\/jats:italic> =\u20090.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients (<jats:italic toggle=\"yes\">p<\/jats:italic> =\u20090.003).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32734","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T09:03:56Z","timestamp":1660813436000},"page":"430-442","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation"],"prefix":"10.1097","volume":"77","author":[{"given":"Alix","family":"Demory","sequence":"first","affiliation":[{"name":"Service d'h\u00e9patologie, H\u00f4pital Avicenne, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"},{"name":"Unit\u00e9 de Formation et de Recherche Sant\u00e9 M\u00e9decine et Biologie Humaine, Universit\u00e9 Paris Nord, Paris, France"},{"name":"Centre de Recherche des Cordeliers, Inserm, Sorbonne Universit\u00e9, Universit\u00e9 Paris, INSERM, Functional Genomics of Solid Tumors laboratory, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marie","family":"P\u00e9ron","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9patogastroent\u00e9rologie, h\u00f4pital Rangueil, CHU Toulouse Assistance, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Calderaro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Publique\u2010H\u00f4pitaux de Paris, Henri Mondor\u2010Albert Chenevier University Hospital, Cr\u00e9teil, France"},{"name":"Universit\u00e9 Paris Est Cr\u00e9teil, INSERM, IMRB, Cr\u00e9teil, France"},{"name":"INSERM, Unit U955, Team 18, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janick","family":"Selves","sequence":"additional","affiliation":[{"name":"Service d'anatomopathologie, h\u00f4pital Rangueil, CHU Toulouse Assistance, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima\u2010Zohra","family":"Mokrane","sequence":"additional","affiliation":[{"name":"Service de radiologie, h\u00f4pital Rangueil, CHU Toulouse Assistance, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Amaddeo","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Henri Mondor, Service d'H\u00e9patologie, Cr\u00e9teil, France"},{"name":"Universit\u00e9 Paris Est Cr\u00e9teil, INSERM, IMRB, Cr\u00e9teil, France"},{"name":"INSERM, U955, Equipe 18 \"Physiopathologie et Th\u00e9rapeutiques des H\u00e9patites Virales Chroniques et des cancers li\u00e9s\", Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Paradis","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Beaujon, Service d'anatomopathologie, Clichy, France"},{"name":"Universit\u00e9 de Paris Cit\u00e9, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Ziol","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Formation et de Recherche Sant\u00e9 M\u00e9decine et Biologie Humaine, Universit\u00e9 Paris Nord, Paris, France"},{"name":"Centre de Recherche des Cordeliers, Inserm, Sorbonne Universit\u00e9, Universit\u00e9 Paris, INSERM, Functional Genomics of Solid Tumors laboratory, Paris, France"},{"name":"Service d'anatomopathologie, H\u00f4pital Avicenne, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2802-9652","authenticated-orcid":false,"given":"Olivier","family":"Sutter","sequence":"additional","affiliation":[{"name":"Service de radiologie, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Blaise","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9patologie, H\u00f4pital Avicenne, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Ganne\u2010Carri\u00e9","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9patologie, H\u00f4pital Avicenne, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"},{"name":"Unit\u00e9 de Formation et de Recherche Sant\u00e9 M\u00e9decine et Biologie Humaine, Universit\u00e9 Paris Nord, Paris, France"},{"name":"Centre de Recherche des Cordeliers, Inserm, Sorbonne Universit\u00e9, Universit\u00e9 Paris, INSERM, Functional Genomics of Solid Tumors laboratory, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Vilgrain","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Beaujon, Service de radiologie, Clichy, France"},{"name":"INSERM U1149 \"Centre de Recherche Sur L'inflammation\", CRI, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Cauchy","sequence":"additional","affiliation":[{"name":"INSERM U1149 \"Centre de Recherche Sur L'inflammation\", CRI, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Beaujon, Service de chirurgie h\u00e9pato\u2010biliaire, Clichy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-0334","authenticated-orcid":false,"given":"Jessica","family":"Zucman\u2010Rossi","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Inserm, Sorbonne Universit\u00e9, Universit\u00e9 Paris, INSERM, Functional Genomics of Solid Tumors laboratory, Paris, France"},{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, Service d'Oncologie M\u00e9dicale, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7464-3939","authenticated-orcid":false,"given":"Maxime","family":"Ronot","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Beaujon, Service de radiologie, Clichy, France"},{"name":"INSERM U1149 \"Centre de Recherche Sur L'inflammation\", CRI, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Charles","family":"Nault","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9patologie, H\u00f4pital Avicenne, H\u00f4pitaux Universitaires Paris\u2010Seine\u2010Saint\u2010Denis, Assistance\u2010Publique\u2010H\u00f4pitaux de Paris, Bobigny, France"},{"name":"Unit\u00e9 de Formation et de Recherche Sant\u00e9 M\u00e9decine et Biologie Humaine, Universit\u00e9 Paris Nord, Paris, France"},{"name":"Centre de Recherche des Cordeliers, Inserm, Sorbonne 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retrospective experience of 261 patients","volume":"274","year":"2021","journal-title":"Ann Surg"},{"key":"hep32734-bib-0004-20250824","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1053\/j.gastro.2016.11.042","article-title":"Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation","volume":"152","year":"2017","journal-title":"Gastroenterology"},{"key":"hep32734-bib-0005-20250824","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.hpb.2016.06.011","article-title":"European experience of 573 liver resections for hepatocellular adenoma: a cross\u2010sectional study by the AFC\u2010HCA\u20102013 study group","volume":"18","year":"2016","journal-title":"HPB (Oxford)"},{"key":"hep32734-bib-0006-20250824","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/bjs.8762","article-title":"Systematic review of haemorrhage and rupture of hepatocellular adenomas","volume":"99","year":"2012","journal-title":"Br J Surg"},{"key":"hep32734-bib-0007-20250824","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1053\/j.gastro.2009.07.061","article-title":"A single\u2010center surgical experience of 122 patients with single and multiple hepatocellular adenomas","volume":"137","year":"2009","journal-title":"Gastroenterology"},{"key":"hep32734-bib-0008-20250824","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1478-3231.2011.02667.x","article-title":"Can a decision\u2010making model be justified in the management of hepatocellular adenoma?","volume":"32","year":"2012","journal-title":"Liver Int"},{"key":"hep32734-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jhep.2016.04.001","article-title":"EASL Clinical Practice Guidelines on the management of benign liver tumours","volume":"65","year":"2016","journal-title":"J Hepatol"},{"key":"hep32734-bib-0010-20250824","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/hep.21068","article-title":"Genotype\u2010phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC","volume":"43","year":"2006","journal-title":"Hepatology"},{"key":"hep32734-bib-0011-20250824","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ccr.2014.03.005","article-title":"Genomic profiling of hepatocellular adenomas reveals recurrent FRK\u2010activating mutations and the mechanisms of malignant transformation","volume":"25","year":"2014","journal-title":"Cancer Cell"},{"key":"hep32734-bib-0012-20250824","first-page":"361","article-title":"Long\u2010term evolution of hepatocellular adenomas at MRI follow\u2010up","volume":"292","year":"2020","journal-title":"Radiology"},{"key":"hep32734-bib-0013-20250824","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.14309\/ajg.0000000000000182","article-title":"Development and validation of a model to predict regression of large size hepatocellular adenoma","volume":"114","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"hep32734-bib-0014-20250824","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1111\/liv.14467","article-title":"A multicentre retrospective analysis on growth of residual hepatocellular adenoma after resection","volume":"40","year":"2020","journal-title":"Liver Int"},{"key":"hep32734-bib-0015-20250824","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1002\/bjs.10594","article-title":"Retrospective study on timing of resection of hepatocellular adenoma","volume":"104","year":"2017","journal-title":"Br J Surg"},{"key":"hep32734-bib-0016-20250824","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/hep.21743","article-title":"Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry","volume":"46","year":"2007","journal-title":"Hepatology"},{"key":"hep32734-bib-0017-20250824","article-title":"Long\u2010term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas","volume":"3","year":"2021","journal-title":"JHEP Rep"},{"key":"hep32734-bib-0018-20250824","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/00325481.2022.2051366","article-title":"What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review","volume":"134","year":"2022","journal-title":"Postgrad Med"},{"key":"hep32734-bib-0019-20250824","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1016\/j.jacc.2013.11.004","article-title":"2013 AHA\/ACC\/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines and The Obesity Society","volume":"63","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"hep32734-bib-0020-20250824","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1055\/s-0035-1552581","article-title":"Estrogens, obesity, inflammation, and breast cancer\u2013what is the link?","volume":"33","year":"2015","journal-title":"Semin Reprod Med"},{"key":"hep32734-bib-0021-20250824","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10911-014-9321-0","article-title":"Impact of obesity on mammary gland inflammation and local estrogen production","volume":"19","year":"2014","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"hep32734-bib-0022-20250824","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/j.1365-2559.2007.02862.x","article-title":"Nuclear beta\u2010catenin staining and absence of steatosis are indicators of hepatocellular adenomas with an increased risk of malignancy","volume":"51","year":"2007","journal-title":"Histopathology"},{"key":"hep32734-bib-0023-20250824","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.humpath.2016.10.004","article-title":"Malignant transformation of a \u03b2\u2010catenin inflammatory adenoma due to an S45 \u03b2\u2010catenin\u2010activating mutation present 12\u2009years before","volume":"62","year":"2017","journal-title":"Hum Pathol"},{"key":"hep32734-bib-0024-20250824","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/hep.22995","article-title":"Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience","volume":"50","year":"2009","journal-title":"Hepatology"},{"key":"hep32734-bib-0025-20250824","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1111\/liv.13934","article-title":"Regression of hepatocellular adenoma after bariatric surgery in severe obese patients","volume":"38","year":"2018","journal-title":"Liver Int"},{"key":"hep32734-bib-0026-20250824","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1111\/liv.12925","article-title":"Will weight loss become a future treatment of hepatocellular adenoma in obese patients?","volume":"35","year":"2015","journal-title":"Liver Int"},{"key":"hep32734-bib-0027-20250824","article-title":"KETOgenic diet therapy in patients with HEPatocellular adenoma: study protocol of a matched interventional cohort study","volume":"12","year":"2022","journal-title":"BMJ Open"},{"key":"hep32734-bib-0028-20250824","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1002\/hep.28638","article-title":"Genotype\u2010phenotype correlation of CTNNB1 mutations reveals different \u00df\u2010catenin activity associated with liver tumor progression","volume":"64","year":"2016","journal-title":"Hepatology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.32734","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.32734","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.32734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T22:12:12Z","timestamp":1756073532000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.32734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,11]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.32734","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9,11]]},"assertion":[{"value":"2022-06-01","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-05","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}