Brain metabolic and microstructural alterations associated with hepatitis C virus infection, autoimmune hepatitis and primary biliary cholangitis

Abstract

Background and Aims Neuropsychiatric symptoms in hepatitis C (HCV) patients resemble those of patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), whilst the mechanisms behind them are unknown. Here we looked for cerebral metabolic and/or microstructural alterations in patients with HCV, AIH or PBC as possible causes behind these symptoms. Methods Patients with HCV infection (n = 17), AIH (n = 14) or PBC (n = 11) and age‐adjusted healthy controls (n = 18) underwent brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and psychometric assessment of memory and attention. Brain relative proton density (PD) and T2 relaxation time (T2) were determined in 17 regions of interest (ROIs), as were the concentrations of N‐acetyl‐aspartate, choline, creatine, myo‐inositol and glutamine + glutamate in frontal‐ (fWM) and parietal white matter (pWM). One‐way analysis of variance and Kruskal‐Wallis tests were used for group comparison. Correlations between altered neuropsychological findings and MRI/MRS observations were estimated with the Spearman ρ test. Results HCV, AIH and PBC patients revealed similar alterations in brain PD and metabolites compared to controls: significantly decreased PD in 7/17 ROIs in the HCV group, 16/17 ROIs in the PBC group and 14/17 ROIs in the AIH group, significantly increased N‐acetyl‐aspartate in fWM in all patients, significantly increased choline in the PBC group in both fWM and pWM, in the AIH group only in pWM and with a trend in the HCV group in pWM. Correlation analysis did not reveal significant associations between MRI/MRS alterations and neuropsychological dysfunction. Conclusion The findings suggest similar pathophysiological mechanisms behind neuropsychiatric symptoms associated with HCV infection, AIH and PBC.

WITHDRAWN: Serum biomarkers of liver fibrosis identify changes in striatal metabolite levels

“…Here we demonstrate that in people with APRI or FIB4 identi ed brosis relative to those without serum biomarkers of brosis, levels of striatal Cho and tCr and pontine mI are high. These ndings are consistent with the literature demonstrating higher than control levels of Cho, tCr, and mI in various ROIs, including basal ganglia, in individuals with HCV (Forton et al 2001;Forton et al 2002;McAndrews et al 2005;Reichardt et al 2022). The current study, however, extends the literature by suggesting that liver brosis and not HCV per se is responsible for the elevation in striatal Cho, whereas elevations in mI and tCr may be better explained by the presence of HCV (cf., Table 5).…”

Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms

“…Another study utilizing brain MRI testing and MR spectroscopy have found similar perturbations in brain photon density and increase in metabolites including N-acetyl-aspartate, and choline in regional white matter regions in patients with either AIH, HCV or PBC, raising the possibility of shared pathophysiological mechanisms across these conditions. However in this study, there were no correlations between MRI/MR spectroscopy findings with neuropsychological dysfunction ( Reichardt et al, 2022 ).…”