原発性胆汁性胆管炎

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholangiopathy characterized by inflammation and fibrosis of intrahepatic and/or extrahepatic bile ducts. Its pathogenesis remains incompletely understood, and liver transplantation is currently the only curative treatment available. The diagnosis remains challenging, and no disease-specific biomarkers have been established. Recently, anti-integrin αvβ6 antibodies have emerged as promising serological biomarkers with high specificity for PSC. Advances in imaging modalities, including magnetic resonance cholangiopancreatography and peroral cholangioscopy, have improved diagnostic accuracy for PSC. Although various therapeutic approaches have been investigated, no treatment has been shown to improve the long-term outcomes. Microbiota-targeted therapies represent a promising emerging strategy. The clinical course of PSC, particularly in its early stages, is poorly defined. We propose a definition of early stage PSC consisting of two subtypes: small-duct PSC without liver fibrosis and large-duct PSC without cholestatic enzyme elevation or biliary strictures. Early intervention at this stage may improve the prognosis, thus highlighting the need for further validation.

INTRODUCTION: We sought to evaluate the diagnostic performance of and interassay agreement between a chemiluminescence immunoassay for antimitochondrial antibody subtype M2 (AMA-M2) in patients with primary biliary cholangitis and clinically relevant disease controls with other liver diseases. METHODS: In this retrospective study, 164 patients with primary biliary cholangitis and 403 patients with other liver diseases were enrolled between December 2020 and January 2023. The AMAs were detected using indirect immunofluorescence, line immunoassay (LIA), and chemiluminescence immunoassay. Diagnostic performance was evaluated by sensitivity, specificity, accuracy, and receiver operating characteristic curve analysis. Agreement between methods was assessed using the Cohen κ coefficient and correlation analysis. RESULTS: AMA-M2 detected by chemiluminescence immunoassay had a sensitivity of 84.1%, a specificity of 90.1%, and an accuracy of 88.4%. Our receiver operating characteristic curve analysis showed an area under the curve of 0.927 (95% CI, 0.903-0.951) for AMA-M2 by chemiluminescence immunoassay, which was higher than the area under the curves for AMA-M2 by LIA (0.772) and M2-3E by LIA (0.862) (both P < .001). High concordance was observed between AMA-M2 by chemiluminescence immunoassay and M2-3E by LIA (96.1%, κ = 0.908), with a strong correlation between the 2 assays. DISCUSSION: Chemiluminescence immunoassay-based detection of AMA-M2 showed high diagnostic performance and strong agreement with conventional assays in this cohort, supporting its utility as a reliable quantitative method for clinical diagnosis.

OBJECTIVES: Primary biliary cholangitis (PBC) is an immune-mediated cholangiopathy for which ursodeoxycholic acid (UDCA) improves biochemical outcomes and survival, but its effects on tissue phenotype remain uncertain. We examined whether morphology and marker expression change with UDCA status or primarily reflect disease severity. DESIGN: We studied 109 specimens (biopsies and explants) from 67 patients with PBC: 9 same-episode PRE-POST pairs for the primary paired analysis and all 109 specimens for secondary cross-sectional analysis. Semiquantitative scores were analyzed using exact Wilcoxon signed-rank tests and proportional-odds ordinal regression with patient-clustered robust standard errors and Benjamini-Hochberg correction. RESULTS: Among 9 paired patients, no feature differed PRE-POST (all q = 1.00), including CK7 (P = .125), CK19 (P = .25), and fibrosis (P = .656). However, 80%-power minimum detectable differences were 0.89 (S100) and 1.19 (CD1a) units on a 0-3 scale, limiting inference. In fibrosis-adjusted cross-sectional models, UDCA status was not associated with any marker (all q ≥ .95), whereas fibrosis was associated with CK7 (OR 1.37, 95% CI 1.11-1.69; q = .007), CK19 (OR 1.79, 1.45-2.22; q < .001), and CD1a⁺ density (OR 1.31, 1.09-1.57; q = .007); CP grade was exploratory (OR 1.21; q = .021). After explant adjustment, CK7 and CK19 associations persisted, whereas CD1a⁺ and CP grade did not; S100⁺ was not significant in either model. CONCLUSIONS: Fibrosis stage, not UDCA status, was the principal correlate of biliary epithelial marker expression. No within-patient change was detected, although changes below one-third of the scoring scale could not be excluded. CK7 and CK19 primarily reflect disease stage rather than treatment effect.

PURPOSE: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently accompanied by severe fatigue. This exploratory and feasibility SOMA.LIV substudy examined associations between subjective fatigue, psychological factors, heart rate variability (HRV), and physical performance during a brief stair-climbing task in PBC. Fatigue in this study refers to self-reported fatigue, with a focus on subjective post-exertional and post-recovery fatigue in relation to baseline disease-related fatigue. PATIENTS AND METHODS: The analysis included 42 participants with PBC (93% female; mean age 56 years) who performed a stair-climbing task with continuous heart rate and HRV monitoring. Self-reports assessed fatigue (pre-, post-, post-recovery), anticipated fatigue, and fear of movement. HRV indices were measured at rest and recovery. Correlational and regression analyses identified predictors of fatigue and task performance. RESULTS: Psychological factors and HRV were unrelated to performance. Anticipated fatigue strongly predicted post-task fatigue (β = 0.69, p <0.001), while post-task fatigue predicted fatigue after recovery (β = 0.61, p <0.001). HRV indices showed no association with fatigue. CONCLUSION: Findings suggest that fatigue responses to brief physical exertion in individuals with PBC are driven partly by cognitive-affective expectations, particularly anticipated fatigue, while fear of movement showed only a trend-level association. These results should be interpreted in light of the study's limitations, including sample size and methodological constraints. Future studies should use larger samples and more demanding exertion paradigms to further elucidate mechanisms underlying exertion-related fatigue in PBC.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease lacking noninvasive biomarkers that adequately reflect disease status. CD161 is an immunoregulatory molecule expressed on T and NK cells, but its soluble (sCD161) and membrane-bound (mCD161) forms remain poorly characterized in PBC. We measured serum sCD161 and cellular mCD161 in patients with PBC, patients with post-hepatitis B cirrhosis (PHBC), and healthy controls (HCs), and examined CD161 expression in a PBC mouse model. Serum sCD161 was markedly elevated in patients with PBC compared with both patients with PHBC and HCs. It correlated positively with the Mayo score, total bilirubin, direct bilirubin, and red cell distribution width and negatively with apolipoprotein A1, albumin, and platelet count. ROC analysis yielded an AUC of 0.8851, with 80.88% sensitivity and 86.79% specificity. The AUC for sCD161 was numerically higher than that for GGT but slightly lower than that for ALP. In contrast, mCD161 expression was reduced across multiple peripheral T-cell subsets. CD161 mRNA levels remained unchanged, whereas ADAM10/17 inhibition reduced sCD161 release and increased cell-surface mCD161 expression, supporting a role for proteolytic shedding in these reciprocal alterations. Reduced CD161 expression was also observed in T-cell subsets from the liver and spleen of PBC model mice, and multiplex immunofluorescence showed fewer hepatic CD4⁺CXCR5⁺CD161⁺ cells. These findings support the potential of sCD161 as an adjunctive biomarker for PBC diagnosis and disease assessment.