{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:05:31Z","timestamp":1780031131966,"version":"3.53.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Langerhans cell histiocytosis (LCH) is a clonal myeloid neoplasm with variable outcomes; hepatic involvement is uniformly classified as high-risk. However, liver disease includes distinct structural and biochemical phenotypes with unclear prognostic significance. This study aimed to identify prognostic determinants in pediatric hepatic LCH, define phenotype-specific risk, and assess whether Z-score\u2013standardized liver size independently predicts disease course and treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 453 children with LCH treated at Children\u2019s Cancer Hospital, Egypt, between 2007 and 2021. Patients received the LCH-III protocol before 2012 and the LCH-IV protocol thereafter. Liver involvement was evaluated using baseline biochemical tests and ultrasonography, and liver span Z-scores were calculated to standardize hepatomegaly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty patients had hepatic involvement: 27 presented with hepatomegaly and preserved liver function, while 53 had hepatic dysfunction. Hepatic dysfunction independently predicted initial treatment failure (OR 9.28; 95% CI, 2.21\u201364.3; p = 0.001) and was associated with markedly inferior 5-year overall survival (OS) (39.4% vs 92.6%) and event-free survival (EFS) (12.9% vs 70.4%) compared with those with hepatomegaly and preserved function (all p&amp;lt; 0.0001). In addition, hypoalbuminemia emerged as an adverse biochemical prognostic factor (HR 4.40; 95% CI, 1.52\u201312.7; p = 0.003). Multivariable analysis demonstrated that week 6 non-response was the only independent predictor of both OS (HR 3.17; 95% CI, 1.37\u20137.31; p = 0.007) and EFS (HR 9.26; 95% CI, 4.12\u201320.84; p&amp;lt; 0.001). Conversely, outcomes were not affected by the extent of hepatomegaly, suggesting that liver size alone does not confer prognostic significance in the absence of functional hepatic impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In pediatric LCH, hepatic dysfunction, rather than hepatomegaly, emerges as the true determinant of high-risk liver involvement. Lake of early response at week 6 independently predicts inferior outcomes. Children with preserved liver function demonstrate excellent outcomes irrespective of liver size. These findings suggest potential refinement of current risk definitions and support a shift toward function-based risk stratification, pending validation in larger, multicenter prospective studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1813004","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:54:17Z","timestamp":1780030457000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and functional hepatic factors as prognostic indicators in children with Langerhans cell histiocytosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Seham","family":"Hassan","sequence":"first","affiliation":[{"name":"Pediatric Oncology Department, Children\u2019s Cancer Hospital Egypt","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Sedky M","family":"Sedky","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Department, National Research Institute, Children\u2019s Cancer Hospital Egypt","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Salama","sequence":"additional","affiliation":[{"name":"Pathology Department, National Cancer Institute, Children\u2019s Cancer Hospital Egypt, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Zaky","sequence":"additional","affiliation":[{"name":"Radiology Department, National Cancer Institute, Children\u2019s Cancer Hospital Egypt, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany","family":"Girguis","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Children\u2019s Cancer Hospital Egypt","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Abd ELKarim","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Children\u2019s Cancer Hospital Egypt","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"ELHaddad","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Department, National Cancer Institute, Children\u2019s Cancer Hospital Egypt, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1607548","article-title":"Langerhans-cell histiocytosis","volume":"379","author":"Allen","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-690636","article-title":"Revised classification of histiocytosis and 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