{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:53Z","timestamp":1793121233161,"version":"4.5.0"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"12","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200428"],"award-info":[{"award-number":["32200428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220778"],"award-info":[{"award-number":["BK20220778"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-0357_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The clinical implications of positive anti-mitochondrial antibodies (AMAs) and\/or primary biliary cholangitis (PBC)-specific anti-nuclear antibodies (ANAs) in patients with normal alkaline phosphatase (ALP) remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0357_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients at The Second Hospital of Nanjing with positive AMAs\/PBC-ANAs and normal ALP levels from January 2016 to July 2024 were categorized into three groups based on autoantibody profiles: [AMA\/AMA-M2]\n                      <jats:sup>+<\/jats:sup>\n                      [gp210\/sp100]\n                      <jats:sup>+<\/jats:sup>\n                      , [AMA\/AMA-M2]\n                      <jats:sup>+<\/jats:sup>\n                      [gp210\/sp100]\n                      <jats:sup>\u2212<\/jats:sup>\n                      , and [AMA\/AMA-M2]\n                      <jats:sup>\u2212<\/jats:sup>\n                      [gp210\/sp100]\n                      <jats:sup>+<\/jats:sup>\n                      . The study compared PBC diagnostic rates, clinical symptoms, laboratory results, and pathology across these groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0357_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 53.3\u202f% (88\/165) of the patients showed cholangitis activity diagnosed of PBC. The PBC diagnosis rate in the three groups was 82.1\u202f% (23\/28), 48.4\u202f% (46\/95), and 45.2\u202f% (19\/42) respectively. Multivariate analysis indicated a significant association between the absence of liver disease-related etiology (p&lt;0.001), baseline serum immunoglobulin M (IgM) exceeding 0.796\u00a0times the upper limit of normal (ULN) (p&lt;0.001), and the diagnosis of PBC as determined by liver biopsy. In the three groups of non-PBC patients, the major pathological injury patterns were minor nonspecific reactive changes (40.0\u202f%\/28.6\u202f%\/39.1\u202f%), inflammation (40.0\u202f%\/24.5\u202f%\/47.8\u202f%), and fatty changes (20\u202f%\/20.4\u202f%\/4.3\u202f%). The diagnosis included viral hepatitis, autoimmune hepatitis, fatty liver disease, vascular liver disorders, drug-induced liver injury, congenital hepatic fibrosis, and porphyria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0357_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Over 50\u202f% of patients with positive PBC-specific antibodies and normal ALP have PBC. Liver biopsy is recommended when AMAs and\/or PBC-specific ANAs are positive, especially when baseline serum IgM exceeds 0.796\u00a0\u00d7\u00a0ULN, and when other etiologies related to liver disease are absent. The area under the curve (AUC) for these three indicators reaches\u00a00.84.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-0357","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T18:56:55Z","timestamp":1755629815000},"page":"2501-2512","source":"Crossref","is-referenced-by-count":4,"title":["Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels"],"prefix":"10.1515","volume":"63","author":[{"given":"Shasha","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Clinical Teaching Hospital of Medical School, Nanjing University , Nanjing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Southeast University , Nanjing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3214-0038","authenticated-orcid":false,"given":"Yongfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Liver Disease , The Second Hospital of Nanjing, Clinical Teaching Hospital of Medical School, Nanjing University , Nanjing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"2025110712102416083_j_cclm-2025-0357_ref_001","doi-asserted-by":"crossref","unstructured":"Alvaro, D, Carpino, G, Craxi, A, Floreani, A, Moschetta, A, Invernizzi, P. Primary biliary cholangitis management: controversies, perspectives and daily practice implications from an expert panel. Liver Int 2020;40:2590\u2013601. https:\/\/doi.org\/10.1111\/liv.14627.","DOI":"10.1111\/liv.14627"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_002","doi-asserted-by":"crossref","unstructured":"Zandanell, S, Strasser, M, Feldman, A, Tevini, J, Strebinger, G, Niederseer, D, et al.. Low rate of new-onset primary biliary cholangitis in a cohort of anti-mitochondrial antibody-positive subjects over six years of follow-up. J\u00a0Intern Med 2020;287:395\u2013404. https:\/\/doi.org\/10.1111\/joim.13005.","DOI":"10.1111\/joim.13005"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_003","doi-asserted-by":"crossref","unstructured":"Dahlqvist, G, Gaouar, F, Carrat, F, Meurisse, S, Chazouilleres, O, Poupon, R, et al.. Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis. Hepatology 2017;65:152\u201363. https:\/\/doi.org\/10.1002\/hep.28859.","DOI":"10.1002\/hep.28859"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_004","doi-asserted-by":"crossref","unstructured":"Duan, W, Chen, S, Li, S, Lv, T, Li, B, Wang, X, et al.. The future risk of primary biliary cholangitis (PBC) is low among patients with incidental anti-mitochondrial antibodies but without baseline PBC. Hepatol Commun 2022;6:3112\u20139. https:\/\/doi.org\/10.1002\/hep4.2067.","DOI":"10.1002\/hep4.2067"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_005","doi-asserted-by":"crossref","unstructured":"Mitchison, HC, Bassendine, MF, Hendrick, A, Bennett, MK, Bird, G, Watson, AJ, et al.. Positive antimitochondrial antibody but normal alkaline phosphatase: is this primary biliary cirrhosis? Hepatology 1986;6:1279\u201384. https:\/\/doi.org\/10.1002\/hep.1840060609.","DOI":"10.1002\/hep.1840060609"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_006","doi-asserted-by":"crossref","unstructured":"Sun, C, Xiao, X, Yan, L, Sheng, L, Wang, Q, Jiang, P, et al.. Histologically proven AMA positive primary biliary cholangitis but normal serum alkaline phosphatase: is alkaline phosphatase truly a surrogate marker? J\u00a0Autoimmun 2019;99:33\u20138. https:\/\/doi.org\/10.1016\/j.jaut.2019.01.005.","DOI":"10.1016\/j.jaut.2019.01.005"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_007","doi-asserted-by":"crossref","unstructured":"Lindor, KD, Bowlus, CL, Boyer, J, Levy, C, Mayo, M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2019;69:394\u2013419. https:\/\/doi.org\/10.1002\/hep.30145.","DOI":"10.1002\/hep.30145"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_008","doi-asserted-by":"crossref","unstructured":"Zhang, Y, Jin, Y, Liu, Y, Wang, M, Xu, A. Diagnostic value of quantitative chemiluminescence immunoassay for anti-gp210 and anti-sp100 antibodies in primary biliary cholangitis. Clin Chem Lab Med 2024;62:e193\u20136. https:\/\/doi.org\/10.1515\/cclm-2023-1490.","DOI":"10.1515\/cclm-2023-1490"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_009","doi-asserted-by":"crossref","unstructured":"Burt, AD, Ferrell, LD, H\u00fcbscher, SG. MacSweens pathology of the liver. Histopathology 1996;29:587.","DOI":"10.1046\/j.1365-2559.1996.d01-542.x"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_010","doi-asserted-by":"crossref","unstructured":"Tanaka, A, Ma, X, Takahashi, A, Vierling, JM. Primary biliary cholangitis. Lancet 2024;404:1053\u201366. https:\/\/doi.org\/10.1016\/s0140-6736(24)01303-5.","DOI":"10.1016\/S0140-6736(24)01303-5"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_011","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver. Electronic address EEE, European Association for the Study of the L. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J\u00a0Hepatol 2017;67:145\u201372. https:\/\/doi.org\/10.1016\/j.jhep.2017.03.022.","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_012","doi-asserted-by":"crossref","unstructured":"Nakanuma, Y, Zen, Y, Harada, K, Sasaki, M, Nonomura, A, Uehara, T, et al.. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: interobserver agreement. Pathol Int 2010;60:167\u201374. https:\/\/doi.org\/10.1111\/j.1440-1827.2009.02500.x.","DOI":"10.1111\/j.1440-1827.2009.02500.x"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_013","doi-asserted-by":"crossref","unstructured":"Terziroli Beretta-Piccoli, B, Stirnimann, G, Mertens, J, Semela, D, Zen, Y, Mazzucchelli, L, et al.. Primary biliary cholangitis with normal alkaline phosphatase: a neglected clinical entity challenging current guidelines. J\u00a0Autoimmun 2021;116:102578. https:\/\/doi.org\/10.1016\/j.jaut.2020.102578.","DOI":"10.1016\/j.jaut.2020.102578"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_014","doi-asserted-by":"crossref","unstructured":"Trivedi, PJ, Hirschfield, GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021;70:1989\u20132003. https:\/\/doi.org\/10.1136\/gutjnl-2020-322362.","DOI":"10.1136\/gutjnl-2020-322362"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_015","doi-asserted-by":"crossref","unstructured":"Chang, Y, Guo, C, Guo, G, Yuan, Z, Zhou, X, Wang, J, et al.. Erythrocyte count is associated with prognosis in Chinese patients with primary biliary cholangitis. Exp Ther Med 2020;19:2075\u201382. https:\/\/doi.org\/10.3892\/etm.2020.8446.","DOI":"10.3892\/etm.2020.8446"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_016","doi-asserted-by":"crossref","unstructured":"Wang, LL, Wei, TT, Yin, JR, Qin, BD, Ma, N, Tang, QQ, et al.. Red blood cell distribution width and mean platelet volume are potential prognostic indices for patients with primary biliary cirrhosis. Clin Chem Lab Med 2017;55:e127\u20139. https:\/\/doi.org\/10.1515\/cclm-2016-0680.","DOI":"10.1515\/cclm-2016-0680"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_017","doi-asserted-by":"crossref","unstructured":"Ito, T, Ishigami, M, Morooka, H, Yamamoto, K, Imai, N, Ishizu, Y, et al.. The albumin-bilirubin score as a predictor of outcomes in Japanese patients with PBC: an analysis using time-dependent ROC. Sci Rep 2020;10:17812. https:\/\/doi.org\/10.1038\/s41598-020-74732-3.","DOI":"10.1038\/s41598-020-74732-3"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_018","doi-asserted-by":"crossref","unstructured":"Prince, M, Chetwynd, A, Newman, W, Metcalf, JV, James, OF. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28\u00a0years. Gastroenterology 2002;123:1044\u201351. https:\/\/doi.org\/10.1053\/gast.2002.36027.","DOI":"10.1053\/gast.2002.36027"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_019","doi-asserted-by":"crossref","unstructured":"Ding, D, Xuan, G, Hu, Y, Yu, J, Liu, Y, Guo, G, et al.. Immunoglobulin M: a neglected serum biomarker in treatment-naive primary biliary cholangitis with normal alkaline phosphatase. Hepatol Commun 2022;6:1403\u201312. https:\/\/doi.org\/10.1002\/hep4.1907.","DOI":"10.1002\/hep4.1907"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_020","doi-asserted-by":"crossref","unstructured":"Li, M, Chen, S, Li, S, Lv, T, Li, B, Shan, S, et al.. Add-on immunosuppressive therapy may benefit selected patients with primary biliary cholangitis and autoimmune phenomena. Therap Adv Gastroenterol 2024;17. https:\/\/doi.org\/10.1177\/17562848231224840.","DOI":"10.1177\/17562848231224840"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_021","doi-asserted-by":"crossref","unstructured":"Gerussi, A, Bernasconi, DP, O\u2019Donnell, SE, Lammers, WJ, Van Buuren, H, Hirschfield, G, et al.. Measurement of gamma glutamyl transferase to determine risk of liver transplantation or death in patients with primary\u00a0biliary cholangitis. Clin Gastroenterol Hepatol 2021;19:1688\u201397 e14. https:\/\/doi.org\/10.1016\/j.cgh.2020.08.006.","DOI":"10.1016\/j.cgh.2020.08.006"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_022","doi-asserted-by":"crossref","unstructured":"Zhu, YJ, Li, J, Liu, YG, Jiang, Y, Cheng, XJ, Han, X, et al.. Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis. World J Gastroenterol 2023;29:5075\u201381. https:\/\/doi.org\/10.3748\/wjg.v29.i34.5075.","DOI":"10.3748\/wjg.v29.i34.5075"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_023","doi-asserted-by":"crossref","unstructured":"Corpechot, C, Lemoinne, S, Soret, PA, Hansen, B, Hirschfield, G, Gulamhusein, A, et al.. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: to what extent and\u00a0under what conditions is normal alkaline phosphatase level associated with complication-free survival gain? Hepatology 2024;79:39\u201348. https:\/\/doi.org\/10.1097\/hep.0000000000000529.","DOI":"10.1097\/HEP.0000000000000529"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_024","doi-asserted-by":"crossref","unstructured":"Berdichevski, T, Cohen-Ezra, O, Pappo, O, Ben-Ari, Z. Positive antimitochondrial antibody but normal serum alkaline phosphatase levels: could it be primary biliary cholangitis? Hepatol Res 2017;47:742\u20136. https:\/\/doi.org\/10.1111\/hepr.12809.","DOI":"10.1111\/hepr.12809"},{"key":"2025110712102416083_j_cclm-2025-0357_ref_025","doi-asserted-by":"crossref","unstructured":"Worman, HJ, Courvalin, JC. Antinuclear antibodies specific for primary biliary cirrhosis. Autoimmun Rev 2003;2:211\u20137. https:\/\/doi.org\/10.1016\/s1568-9972(03)00013-2.","DOI":"10.1016\/S1568-9972(03)00013-2"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0357\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:10:40Z","timestamp":1762517440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0357\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,9,16]]},"published-print":{"date-parts":[[2025,11,25]]}},"alternative-id":["10.1515\/cclm-2025-0357"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2025-0357","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}