{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:16:43Z","timestamp":1788337003898,"version":"build-2803163510"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"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":["Hepatology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Autoimmune polyendocrinopathy\u2010candidiasis\u2010ectodermal dystrophy (APECED), caused by autoimmune regulator (<jats:italic toggle=\"yes\">AIRE<\/jats:italic>) mutations, manifests with chronic mucocutaneous candidiasis (CMC) and multisystem autoimmunity, most often hypoparathyroidism (HP) and adrenal insufficiency (AI). European cohorts previously reported a ~10% prevalence of APECED\u2010associated hepatitis (APAH) with presentations ranging from asymptomatic laboratory derangements to fatal fulminant hepatic failure. Herein, we characterized APAH in a large APECED cohort from the Americas.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Forty\u2010five consecutive patients with APECED were evaluated (2013\u20102015) at the National Institutes of Health (NIH; NCT01386437). Hepatology consultation assessed hepatic and autoimmune biomarkers and liver ultrasound in all patients. Liver biopsies evaluated autoimmune features and fibrosis. The 16S ribosomal RNA (rRNA) sequencing was performed in 35 patients\u2019 stools (12 with and 23 without APAH). Among 43 evaluable patients, 18 (42%) had APAH; in 33.3% of those with APAH, APAH occurred before developing classic APECED diagnostic criteria. At APAH diagnosis, the median age was 7.8\u00a0years, and patients manifested with aminotransferase elevation and\/or hyperbilirubinemia. All patients with APAH were in clinical remission during their NIH evaluation while receiving immunomodulatory treatment. We found no difference in age, sex, or prevalence of CMC, AI, or HP between patients with or without APAH. Autoantibody positivity against aromatic L\u2010amino acid decarboxylase, cytochrome P450 family 1 subfamily A member 2, histidine decarboxylase (HDC), bactericidal\/permeability\u2010increasing fold\u2010containing B1, tryptophan hydroxlase, and 21\u2010hydroxylase (21\u2010OH), and the homozygous c.967_979del13 <jats:italic toggle=\"yes\">AIRE<\/jats:italic> mutation were associated with APAH development. Classical serological biomarkers of autoimmune hepatitis (AIH) were only sporadically positive. AIH\u2010like lymphoplasmacytic inflammation with mild fibrosis was the predominant histological feature. Stool microbiome analysis found <jats:italic toggle=\"yes\">Slackia<\/jats:italic> and <jats:italic toggle=\"yes\">Acidaminococcus<\/jats:italic> in greater abundance in patients with APAH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>APAH is more common than previously described, may present early before classic APECED manifestations, and most often manifests with milder, treatment\u2010responsive disease. Several APECED\u2010associated autoantibodies, but not standard AIH\u2010associated biomarkers, correlate with APAH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31421","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T17:05:32Z","timestamp":1592413532000},"page":"1088-1104","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["APECED\u2010Associated Hepatitis: Clinical, Biochemical, Histological and Treatment Data From a Large, Predominantly American Cohort"],"prefix":"10.1097","volume":"73","author":[{"given":"David M.","family":"Chascsa","sequence":"first","affiliation":[{"name":"Translational,Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise M. N.","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section,Laboratory of Clinical Immunology and Microbiology,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis","family":"Hadjiyannis","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section,Laboratory of Clinical Immunology and Microbiology,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawwa","family":"Alao","sequence":"additional","affiliation":[{"name":"Translational,Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-7306","authenticated-orcid":false,"given":"Mukil","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section,Laboratory of Clinical Immunology and Microbiology,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Quinones","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Bioscience Branch,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology,Center for Cancer Research,National Cancer Institute,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Simcox","sequence":"additional","affiliation":[{"name":"Translational,Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Chitsaz","sequence":"additional","affiliation":[{"name":"Translational,Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey R.","family":"Rose","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section,Laboratory of Clinical Immunology and Microbiology,National Institute of Allergy and Infectious Diseases,National Institutes of 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