Anxiety plays a negative role in UDCA treatment efficacy in primary biliary cholangitis

Anxiety is a comorbid condition associated with the adverse effects in patients with primary biliary cholangitis (PBC), whereas the underlying mechanisms remain unclear. We sought to elucidate the influence of anxiety on the therapeutic response to UDCA in PBC patients and mice model. Anxiety was assessed using the Hamilton Anxiety Scale (HAMA). Least absolute shrinkage and selection operator (Lasso)-logistic regression model was employed to explore the effect of anxiety on UDCA efficacy. Further, the role of chronic restraint stress (CRS)-induced anxiety-like behaviors on UDCA efficacy was evaluated in dnTGFβRII mice, a well-recognized model of PBC. In this study, anxiety was observed to be a common phenomenon in patients with PBC who were newly diagnosed (141/284, 49.6%). PBC patients with anxiety were more likely to exhibit an inadequate response to UDCA therapy, as evaluated by the Paris-II criteria (53.9% vs. 78.3%; P < 0.001). The Lasso-logistic regression model identified the pre-treatment HAMA score as a risk predictor for non-response to UDCA therapy. Meanwhile, higher HAMA scores correlated with increased proportions of circulating follicular T helper (Tfh) cells. In line with observations in patients, CRS intervention promoted the infiltration of Tfh cells and played a negative role in UDCA treatment efficacy in dnTGFβRII mice. In conclusion, anxiety is a risk factor for inadequate response to UDCA treatment in PBC. To facilitate early identification of patients at risk for inadequate UDCA efficacy before treatment begins, it is crucial to screen for anxiety in patients with PBC.