{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:40:55Z","timestamp":1789656055495,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: A protein called \u2018apoptosis inhibitor of macrophage (AIM)\u2019 is involved in the pathogenesis of obesity-associated disease. Although it is widely recognized that concurrent obesity affects the disease progression of chronic liver disease, as does concurrent type 2 diabetes mellitus (T2DM), the involvement of AIM in the pathogenesis of obesity or insulin resistance is not yet understood in patients with primary biliary cholangitis (PBC). Methods: Obesity was defined as a body mass index (BMI) exceeding 25, and insulin resistance was defined as a homeostasis model assessment for insulin resistance (HOMA-IR) value exceeding 2.0, respectively. Hepatic steatosis was estimated based on the classification proposed by Brunt and colleagues. The histological stage was determined by Scheuer\u2019s classification. Results: Twelve (25.0%) of the forty-eight PBC patients had concurrent obesity, and seven (14.6%) had concurrent T2DM. The PBC patients with obesity had significantly higher frequency of hepatic steatosis. Compared to the patients without T2DM, those with concurrent T2DM had significantly higher serum ALT levels and more advanced histological stages. The patients\u2019 serum AIM levels were not associated with concurrent obesity or concurrent T2DM. Our analyses identified the following as the factors that significantly affected the patients\u2019 AIM levels: serum immunoglobulin G, albumin, tumor necrosis factor-\u03b1 levels, and the histological stages. Conclusions: These results indicate that AIM may not be involved in obesity or insulin resistance, but it may be associated with the disease severity of PBC.<\/jats:p>","DOI":"10.3390\/jcm15031169","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:38:12Z","timestamp":1770046692000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Involvement of Apoptosis Inhibitor of Macrophage in the Disease Severity of Primary Biliary Cholangitis"],"prefix":"10.3390","volume":"15","author":[{"given":"Takashi","family":"Himoto","sequence":"first","affiliation":[{"name":"Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9390-7565","authenticated-orcid":false,"given":"Koji","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-0479","authenticated-orcid":false,"given":"Shima","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-386X","authenticated-orcid":false,"given":"Tomoko","family":"Tadokoro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-7240","authenticated-orcid":false,"given":"Kyoko","family":"Oura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-3045","authenticated-orcid":false,"given":"Asahiro","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Kobara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1007\/s10620-015-3760-3","article-title":"Concurrent obesity, diabetes, and steatosis increase risk of advanced fibrosis among HCV patients: A systemic review","volume":"60","author":"Dyal","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/apt.14273","article-title":"The higher prevalence of truncal obesity and diabetes in American than Chinese patients with chronic hepatitis C might contribute to more rapid progression to advanced liver disease","volume":"46","author":"Rao","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yu, S.J., Kim, W., Kim, D., Yoon, J.-H., Lee, K., Kim, J.H., Cho, E.J., Lee, J.-H., Kim, H.Y., and Kim, Y.J. (2015). Visceral obesity predicts significant fibrosis in patients with nonalcoholic fatty liver disease. Medicine, 94.","DOI":"10.1097\/MD.0000000000002159"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.cgh.2018.07.006","article-title":"Obesity and weight gain are associated with progression of fibrosis in patients with nonalcoholic fatty liver disease","volume":"17","author":"Kim","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s00535-010-0249-x","article-title":"Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis","volume":"45","author":"Sorrentino","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MCG.0b013e318261e659","article-title":"Primary biliary cirrhosis is more severe in overweight patients","volume":"47","author":"Hindi","year":"2013","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1055\/s-0039-1697617","article-title":"The pathogenesis of primary biliary cholangitis: A comprehensive review","volume":"40","author":"Lleo","year":"2020","journal-title":"Semin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/apt.14327","article-title":"Significant burden of nonalcoholic fatty liver disease with advanced fibrosis in the US: A cross-sectional analysis of 2011\u20132014 National Health and Nutrition Examination Survey","volume":"46","author":"Wong","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.4254\/wjh.v12.i9.533","article-title":"Clinical implications, diagnosis, and management of diabetes in patients with liver diseases","volume":"12","author":"Chung","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gremese, E., Tolusso, B., Gigante, M.R., and Ferraccioli, G. (2014). Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammatory diseases). Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00576"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.autrev.2014.07.001","article-title":"Obesity in autoimmune diseases:not a passive bystander","volume":"13","author":"Versini","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1002\/art.23600","article-title":"Inflammation-associated insulin resistance: Differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms","volume":"58","author":"Chung","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_13","first-page":"885","article-title":"Insulin resistance in systemic lupus erythematosus patients: Contributing factors and relationship with subclinical atherosclerosis","volume":"35","author":"Delgado","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.189.2.413","article-title":"Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily","volume":"189","author":"Miyazaki","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12072","DOI":"10.1073\/pnas.1101841108","article-title":"Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue","volume":"109","author":"Kurokawa","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1007\/s00535-017-1398-y","article-title":"Activation of apoptosis inhibitor of macrophage is a sensitive diagnostic marker for NASH-associated hepatocellular carcinoma","volume":"53","author":"Koyama","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.celrep.2013.03.006","article-title":"Obesity-associated autoantibody production requires AIM to retain immunoglobulin M immune complex on follicular dendritic cells","volume":"3","author":"Arai","year":"2013","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/hep.30145","article-title":"Primary biliary cholangitis: 2018 practice guideline from American Association for the Study of Liver Diseases","volume":"69","author":"Lindor","year":"2019","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S0168-8278(99)80297-9","article-title":"International Autoimmune Hepatitis Group Report: Review of criteria for a diagnosis of autoimmune hepatitis","volume":"31","author":"Alvarez","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Committee of the Japan Diabetes Society on the Diagnosis Criteria of Diabetes Mellitus, Seino, Y., Nanjo, K., Tajima, N., Kadowaki, T., Kashiwagi, A., Araki, E., Ito, C., Inagaki, N., and Iwamoto, Y. (2010). Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J. Diabetes Investig., 1, 212\u2013228.","DOI":"10.1111\/j.2040-1124.2010.00074.x"},{"key":"ref_21","first-page":"987","article-title":"Examination Committee of Criteria for \u2018Obesity Disease\u2019 in Japan: Japan Society for the Study of Obesity. New criteria for \u2018obesity disease\u2019 in Japan","volume":"66","author":"Yuji","year":"2002","journal-title":"Circ. J."},{"key":"ref_22","first-page":"1257","article-title":"Primary biliary cirrhosis","volume":"60","author":"Scheuer","year":"1967","journal-title":"Proc. R Soc. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1097\/MEG.0000000000002785","article-title":"Coexistence of metabolic-associated fatty liver disease and autoimmune or toxic liver disease","volume":"36","author":"Danielsson","year":"2024","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Steinmann, S., Hartl, J., Weidemann, S., F\u00fcssel, K., Kroll, C., Sebode, M., Lohse, A.W., and Schramm, C. (2023). Accuracy of controlled attenuation of parameter measurement for the detection of steatosis in autoimmune liver diseases. JHEP Rep., 5.","DOI":"10.1016\/j.jhepr.2023.100898"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1111\/jgh.15936","article-title":"The impact of body mass index on clinicopathological features of nonalcoholic fatty liver disease in Taiwan","volume":"37","author":"Lin","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1046\/j.1463-1326.2003.00256.x","article-title":"The impact of diabetes and obesity on liver histology in patients with hepatitis C","volume":"5","author":"Friedenberg","year":"2003","journal-title":"Diabetes Obes. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1073\/pnas.1220180110","article-title":"Intestinal alkaline phosphatase prevents metabolic syndrome in mice","volume":"110","author":"Kaliannan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1177\/0961203310375439","article-title":"Characteristics and risk factors for hyperglycemia in Chinese female patients with systemic lupus erythematosus","volume":"19","author":"Zeng","year":"2010","journal-title":"Lupus"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1053\/j.gastro.2003.08.032","article-title":"Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression","volume":"125","author":"Hui","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yamazaki, T., Mori, M., Arai, S., Tateishi, R., Abe, M., Ban, M., Nishijima, A., Maeda, M., Asano, T., and Kai, T. (2014). Circulating AIM as an indicator of liver damage and hepatocellular carcinoma in humans. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109123"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mera, K., Uto, H., Mawatani, S., Ido, A., Yoshimine, Y., Nosaki, T., Oda, K., Tabu, K., Kumagai, K., and Tamai, T. (2014). Serum levels of apoptosis inhibitor of macrophage are associated with hepatic fibrosis in patients with chronic hepatitis C. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-14-27"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Z., Li, Y., Ren, L., Li, Y., Xu, T., Li, W., Gao, W., Sun, G., and Liu, M. (2024). Clinical performance of AMA-M2, anti-gp210 and anti-Sp100 antibody levels in primary biliary cholangitis: When detected by multiplex bead-based flow fluorescent immunoassay. Immun. Inflamm. Dis., 12.","DOI":"10.1002\/iid3.1161"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.intimp.2018.07.022","article-title":"Elevation of serum CD5L concentration is correlated with disease activity in patients with systemic lupus erythematosus","volume":"63","author":"Lai","year":"2018","journal-title":"Int. Immunopharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:54:17Z","timestamp":1770047657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031169"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031169","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]}}}