Magnetic resonance imaging evidence of hippocampal structural changes in patients with primary biliary cholangitis

Abstract

Introduction: Behavioral symptoms are commonly reported by patients with primary biliary cholangitis (PBC). In other patient populations, symptoms are commonly associated with hippocampal volume reduction linked to neuroinflammation (inferred from regional iron deposition), as demonstrated by magnetic resonance imaging (MRI). We hypothesized that PBC patients would exhibit reduced volume and increased iron deposition of the hippocampus. Methods: Seventeen female non-cirrhotic PBC patients and 17 age/gender-matched controls underwent 3-Tesla T1-weighted MRI and quantitative susceptibility mapping (QSM; an indicator of iron deposition). The hippocampus and its subfields were segmented from T1 images using Freesurfer, and susceptibility of the whole hippocampus was calculated from QSM images. Volume and susceptibility were compared between groups, and associations with PBC-40 score and disease indicators (years since diagnosis, Fibroscan value, alkaline phosphatase level, clinical response to ursodeoxycholic acid (UDCA)) were investigated. Results: PBC patients exhibited significantly reduced hippocampal volume (p = 0.023) and increased susceptibility (p = 0.048). Subfield volumes were reduced for the subiculum, molecular layer, granule cell layer of the dentate gyrus and CA4 (p < 0.05). Fibroscan value was significantly correlated with PBC-40 (Spearman's rho = 0.499; p = 0.041) and disease duration (Spearman's rho = 0.568; p = 0.017). Discussion: Our findings suggest hippocampal changes occur early in the disease course of PBC, similar in magnitude to those observed in major depressive disorder and neurodegenerative diseases. Translational impact: Clinical management of PBC could include early interventional strategies that promote hippocampal neurogenesis that may beneficially impact behavioral symptoms and improve quality of life.