Backgrounds/Aims Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals.
Methods A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC.
Results A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917.
Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.
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Reevaluating the clinical course of AMA-positive patients with normal liver enzymes: A large retrospective cohort study Ahmad Yahia, Fadi Abu Baker, Mifleh Tatour, Rawi Hazzan Annals of Hepatology.2026; 31(1): 102147. CrossRef
Pruritus in Chronic Cholestatic Liver Diseases, Especially in Primary Biliary Cholangitis: A Narrative Review Tatsuo Kanda, Reina Sasaki-Tanaka, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai International Journal of Molecular Sciences.2025; 26(5): 1883. CrossRef
Is AMA M2 a useful serologic test for screening high-risk patients for PBC?: Editorial on “Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive” Nae-Yun Heo Clinical and Molecular Hepatology.2025; 31(2): 640. CrossRef
Correspondence to editorial on “Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive” Haolong Li, Song Liu, Xu Wang, Li Wang, Tengda Xu, Yongzhe Li Clinical and Molecular Hepatology.2025; 31(2): e194. CrossRef
Background/Aims Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet.
Methods Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation.
Results In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL.
Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.
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Both liver parenchymal and non-parenchymal cells express JCAD protein under various circumstances Li Xie, Li Zhang, Hui Chen, Yong-Yu Yang, Jian Wu Clinical and Molecular Hepatology.2024; 30(2): 279. CrossRef
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