{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:54:49Z","timestamp":1787237689405,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005719","name":"Dicle University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005719","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Rheumatol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Liver involvement, particularly autoimmune hepatitis (AIH) overlap, is a rare but clinically important manifestation of systemic sclerosis (SSc). This study aimed to assess the prevalence, clinical characteristics, and diagnostic utility of laboratory parameters for identifying AIH in a cohort of patients with SSc.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We retrospectively analyzed 111 patients with SSc. Clinical characteristics, autoantibody profiles, and laboratory parameters were compared between patients with and without AIH. AIH diagnosis was confirmed by liver biopsy in all cases. Given the small number of events, Firth\u2019s penalized likelihood logistic regression was applied to identify independent risk factors. The diagnostic performance of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum IgG levels was evaluated using receiver operating characteristic (ROC) curve analysis. Prior methotrexate (MTX) exposure was recorded, and the potential confounding effect of MTX-induced liver enzyme elevations was assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Autoimmune hepatitis (AIH) was identified in 8 of 111 patients (7.2%). All AIH-positive patients showed interface hepatitis on liver biopsy. There were no significant differences between AIH-positive and AIH-negative patients regarding age, systemic sclerosis subtype, or presence of interstitial lung disease (all\n p<\/jats:italic>\n \u2009>\u20090.05). Firth\u2019s penalized logistic regression indicated that diffuse cutaneous SSc, anti\u2013Scl-70 positivity, and interstitial lung disease were not independent predictors of AIH overlap. In receiver operating characteristic analysis, alanine aminotransferase (ALT) demonstrated the highest diagnostic performance (AUC 0.88, 95% CI 0.76\u20130.99;\n p<\/jats:italic>\n \u2009<\u20090.001), with a sensitivity of 87.5% and specificity of 85.4% at a cut-off\u2009>\u200934.5 U\/L. Aspartate aminotransferase (AST) (AUC 0.86) and serum IgG (AUC 0.74) also showed significant but lower discriminatory ability. ALT retained high specificity for AIH even among patients with prior MTX exposure, supporting its utility as a non-invasive screening tool in SSc.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Autoimmune hepatitis is a rare overlap syndrome in systemic sclerosis that occurs independently of clinical phenotype. Routine monitoring of liver transaminases, particularly ALT, provides a reliable non-invasive screening tool. Clinicians should consider ALT elevations\u2009>\u200934.5 U\/L as a trigger for further AIH evaluation, even in patients with prior MTX exposure.\n \n \n \n \n \n Key Points<\/jats:bold>\n \u2022\u00a0\n Autoimmune hepatitis (AIH) represents a clinically significant overlap in systemic sclerosis (SSc), with a prevalence of 7.2% in this cohort, indicating that it may be more common than previously reported when systematic screening is implemented. Biochemical screening rather than biopsy-only evaluation improves detection.<\/jats:italic>\n \u2022\u00a0\n The development of AIH in SSc patients appears to be independent of disease subtype (limited vs. diffuse), specific autoantibody profiles (Anti-Scl70, ACA), or major organ involvement, such as interstitial lung disease.<\/jats:italic>\n \u2022\u00a0\n An ALT threshold of > 34.5 U\/L provides a practical \u201cred flag\u201d for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. This threshold should be interpreted cautiously in patients with prior methotrexate (MTX) exposure, as mild ALT elevations may also reflect drug-related hepatotoxicity.<\/jats:italic>\n \u2022\u00a0\n An ALT threshold of > 34.5 U\/L provides a practical \u201cred flag\u201d for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated.<\/jats:italic>\n \u2022\u00a0\n Because AIH can develop across the full spectrum of SSc regardless of systemic disease severity, routine monitoring of transaminases is essential for early detection and timely initiation of immunosuppressive therapy.<\/jats:italic>\n <\/jats:td>\n <\/jats:tr>\n <\/jats:tbody>\n <\/jats:table>\n <\/jats:table-wrap>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s10067-026-08014-0","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:01:05Z","timestamp":1772791265000},"page":"2749-2757","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence, clinical features, and laboratory predictors of autoimmune hepatitis in systemic sclerosis: A retrospective single-center cohort study"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2684-165X","authenticated-orcid":false,"given":"Zeynel Abidin","family":"Akar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilan","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"8014_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241814287","author":"J Ko","year":"2023","unstructured":"Ko J, Noviani M, Chellamuthu VR, Albani S, Low AHL (2023) The pathogenesis of systemic sclerosis: the origin of fibrosis and \u0131nterlink with vasculopathy and autoimmunity. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms241814287","journal-title":"Int J Mol Sci"},{"key":"8014_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45100490","author":"G Di Maggio","year":"2023","unstructured":"Di Maggio G, Confalonieri P, Salton F, Trotta L, Ruggero L, Kodric M, Geri P, Hughes M, Bellan M, Gilio M, Lerda S, Baratella E, Confalonieri M, Mondini L, Ruaro B (2023) Biomarkers in systemic sclerosis: an overview. Curr Issues Mol Biol. https:\/\/doi.org\/10.3390\/cimb45100490","journal-title":"Curr Issues Mol Biol"},{"issue":"1","key":"8014_CR3","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1093\/rheumatology\/40.1.102","volume":"40","author":"I Marie","year":"2001","unstructured":"Marie I, Levesque H, Tranvouez JL, Fran\u00e7ois A, Riachi G, Cailleux N, Courtois H (2001) Autoimmune hepatitis and systemic sclerosis: a new overlap syndrome? Rheumatology (Oxford) 40(1):102\u2013106. https:\/\/doi.org\/10.1093\/rheumatology\/40.1.102","journal-title":"Rheumatology (Oxford)"},{"key":"8014_CR4","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i1.60","author":"NK Gatselis","year":"2015","unstructured":"Gatselis NK, Zachou K, Koukoulis GK, Dalekos GN (2015) Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics. World J Gastroenterol. https:\/\/doi.org\/10.3748\/wjg.v21.i1.60","journal-title":"World J Gastroenterol"},{"key":"8014_CR5","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i23.2527","author":"CR Wang","year":"2022","unstructured":"Wang CR, Tsai HW (2022) Autoimmune liver diseases in systemic rheumatic diseases. World J Gastroenterol. https:\/\/doi.org\/10.3748\/wjg.v28.i23.2527","journal-title":"World J Gastroenterol"},{"issue":"8","key":"8014_CR6","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1111\/apt.12470","volume":"38","author":"K Zachou","year":"2013","unstructured":"Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, Fabbri A, Dalekos GN, Muratori L (2013) Review article: autoimmune hepatitis -- current management and challenges. Aliment Pharmacol Ther 38(8):887\u2013913. https:\/\/doi.org\/10.1111\/apt.12470","journal-title":"Aliment Pharmacol Ther"},{"issue":"1-2","key":"8014_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s10354-007-0451-5","volume":"158","author":"A Grassegger","year":"2008","unstructured":"Grassegger A, Pohla-Gubo G, Frauscher M, Hintner H (2008) Autoantibodies in systemic sclerosis (scleroderma): clues for clinical evaluation, prognosis and pathogenesis. Wien Med Wochenschr 158(1\u20132):19\u201328. https:\/\/doi.org\/10.1007\/s10354-007-0451-5","journal-title":"Wien Med Wochenschr"},{"key":"8014_CR8","doi-asserted-by":"crossref","unstructured":"Santos CS, Morales CM, Castro C\u00c1, \u00c1lvarez ED (2023) Clinical phenotype in scleroderma patients based on autoantibodies. Rheumatol Adv Pract. https:\/\/doi.org\/10.1093\/rap\/rkad010","DOI":"10.1093\/rap\/rkad010"},{"issue":"1","key":"8014_CR9","doi-asserted-by":"publisher","first-page":"48","DOI":"10.4166\/kjg.2012.59.1.48","volume":"59","author":"BC You","year":"2012","unstructured":"You BC, Jeong SW, Jang JY, Goo SM, Kim SG, Kim YS, Jeon CH, Jeen YM (2012) Liver cirrhosis due to autoimmune hepatitis combined with systemic sclerosis. Korean J Gastroenterol 59(1):48\u201352. https:\/\/doi.org\/10.4166\/kjg.2012.59.1.48","journal-title":"Korean J Gastroenterol"},{"issue":"8","key":"8014_CR10","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1007\/s10620-009-0996-9","volume":"55","author":"C Efe","year":"2010","unstructured":"Efe C, Ozaslan E, Nasiroglu N, Tunca H, Purnak T, Altiparmak E (2010) The development of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome during the course of connective tissue diseases: report of three cases and review of the literature. Dig Dis Sci 55(8):2417\u20132421. https:\/\/doi.org\/10.1007\/s10620-009-0996-9","journal-title":"Dig Dis Sci"},{"issue":"8","key":"8014_CR11","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1097\/MCG.0b013e318154af74","volume":"42","author":"S L\u00fcth","year":"2008","unstructured":"L\u00fcth S, Herkel J, Kanzler S, Frenzel C, Galle PR, Dienes HP, Schramm C, Lohse AW (2008) Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis. J Clin Gastroenterol 42(8):926\u2013930. https:\/\/doi.org\/10.1097\/MCG.0b013e318154af74","journal-title":"J Clin Gastroenterol"},{"issue":"11","key":"8014_CR12","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","volume":"72","author":"F van den Hoogen","year":"2013","unstructured":"van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American college of rheumatology\/European league against rheumatism collaborative initiative. Ann Rheum Dis 72(11):1747\u201355. https:\/\/doi.org\/10.1136\/annrheumdis-2013-204424","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"8014_CR13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/biomet\/80.1.27","volume":"80","author":"D Firth","year":"1993","unstructured":"Firth D (1993) Bias reduction of maximum likelihood estimates. Biometrika 80(1):27\u201338. https:\/\/doi.org\/10.1093\/biomet\/80.1.27","journal-title":"Biometrika"},{"issue":"2","key":"8014_CR14","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1177\/2397198318802763","volume":"4","author":"G Lepri","year":"2019","unstructured":"Lepri G, Bellando Randone S, Matucci Cerinic M, Allanore Y (2019) Systemic sclerosis and primary biliary cholangitis: an overlapping entity? J Scleroderma Relat Disord 4(2):111\u2013117. https:\/\/doi.org\/10.1177\/2397198318802763","journal-title":"J Scleroderma Relat Disord"},{"issue":"10","key":"8014_CR15","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.3899\/jrheum.090340","volume":"36","author":"S Assassi","year":"2009","unstructured":"Assassi S, Fritzler MJ, Arnett FC, Norman GL, Shah KR, Gourh P, Manek N, Perry M, Ganesh D, Rahbar MH, Mayes MD (2009) Primary biliary cirrhosis (PBC), PBC autoantibodies, and hepatic parameter abnormalities in a large population of systemic sclerosis patients. J Rheumatol 36(10):2250\u20132256. https:\/\/doi.org\/10.3899\/jrheum.090340","journal-title":"J Rheumatol"},{"issue":"3","key":"8014_CR16","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1515\/cclm-2019-0655","volume":"58","author":"L Florin","year":"2020","unstructured":"Florin L, Rubben K, Vanhaecke A, Devreese K, De Keyser F, Smith V, Bonroy C (2020) Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients. Clin Chem Lab Med 58(3):416\u2013423. https:\/\/doi.org\/10.1515\/cclm-2019-0655","journal-title":"Clin Chem Lab Med"},{"issue":"1","key":"8014_CR17","doi-asserted-by":"publisher","first-page":"69","DOI":"10.5021\/ad.2020.32.1.69","volume":"32","author":"HS Han","year":"2020","unstructured":"Han HS, Ahn GR, Kim HJ, Park KY, Li K, Seo SJ (2020) Diffuse systemic sclerosis in a patient with primary biliary cirrhosis and autoimmune hepatitis overlap syndrome: a case report. Ann Dermatol 32(1):69\u201373. https:\/\/doi.org\/10.5021\/ad.2020.32.1.69","journal-title":"Ann Dermatol"},{"issue":"6","key":"8014_CR18","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1111\/j.1365-2036.2012.05223.x","volume":"36","author":"PJ Trivedi","year":"2012","unstructured":"Trivedi PJ, Hirschfield GM (2012) Review article: overlap syndromes and autoimmune liver disease. Aliment Pharmacol Ther 36(6):517\u2013533. https:\/\/doi.org\/10.1111\/j.1365-2036.2012.05223.x","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"8014_CR19","first-page":"108","volume":"6","author":"N Chandok","year":"2010","unstructured":"Chandok N, Silveira MG, Lindor KD (2010) Comparing the simplified and international autoimmune hepatitis group criteria in primary sclerosing cholangitis. Gastroenterol Hepatol N Y 6(2):108\u2013112","journal-title":"Gastroenterol Hepatol N Y"},{"issue":"3","key":"8014_CR20","doi-asserted-by":"publisher","first-page":"100","DOI":"10.14744\/hf.2023.2023.0061","volume":"5","author":"K Moral","year":"2024","unstructured":"Moral K, Simsek B, Tomar VB, Albayrak C, Ergin M, Kilic G, Karatas A, Ekmen N, Kekilli M, Ibis M, Karakan T, Cindoruk M, Esendagli G, Akyol G (2024) Comparison of the recommendation of international autoimmune hepatitis pathology group 2022 and the simplified criteria for autoimmune hepatitis 2008: a preliminary study. Hepatol Forum 5(3):100\u2013105. https:\/\/doi.org\/10.14744\/hf.2023.2023.0061","journal-title":"Hepatol Forum"},{"issue":"1","key":"8014_CR21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/cld.304","volume":"3","author":"MR Lucey","year":"2014","unstructured":"Lucey MR, Vierling JM (2014) Clinical presentation and natural history of autoimmune hepatitis. Clin Liver Dis (Hoboken) 3(1):9\u201311. https:\/\/doi.org\/10.1002\/cld.304","journal-title":"Clin Liver Dis (Hoboken)"},{"issue":"6","key":"8014_CR22","doi-asserted-by":"publisher","first-page":"342","DOI":"10.4103\/1319-3767.145316","volume":"20","author":"P Dhiman","year":"2014","unstructured":"Dhiman P, Malhotra S (2014) Overlap syndromes: an emerging diagnostic and therapeutic challenge. Saudi J Gastroenterol 20(6):342\u2013349. https:\/\/doi.org\/10.4103\/1319-3767.145316","journal-title":"Saudi J Gastroenterol"}],"container-title":["Clinical Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10067-026-08014-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10067-026-08014-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10067-026-08014-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T03:49:42Z","timestamp":1775792982000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10067-026-08014-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["8014"],"URL":"https:\/\/doi.org\/10.1007\/s10067-026-08014-0","relation":{},"ISSN":["0770-3198","1434-9949"],"issn-type":[{"value":"0770-3198","type":"print"},{"value":"1434-9949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"assertion":[{"value":"5 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The study protocol was approved by the Dicle University Medical Faculty Ethics Committee for Non-Interventional Studies (Date: 24.12.2025, Approval Number: 5). The study was based on a retrospective review of anonymized medical records and did not involve direct interventions with human participants. Informed consent was waived by the ethics committee due to the retrospective and anonymized nature of the data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All authors have reviewed and approved the final version of the manuscript, confirming the accuracy and integrity of the work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}