Elevated Plasma BDNF in Early Primary Biliary Cholangitis: Associations with Liver Fibrosis, IL-6, IL-18, Fatigue, and Cognitive Impairment.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations.

METHODS

In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years; 96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated.

RESULTS

Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68-38.07) vs. 5.80 ng/mL (IQR: 4.58-7.54); p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = -0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = -0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity.

CONCLUSIONS

Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further studies are needed to clarify its significance in PBC.