Low blood zinc exacerbates minimal hepatic encephalopathy via altered functional brain activity

BACKGROUND: Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome that significantly affects quality of life. It is associated with neural activity changes, reflected by the amplitude of low-frequency fluctuation (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI). Zinc deficiency compromises cognition; however, its relationship with the neural activity changes in MHE remains unclear. AIMS: To investigate blood zinc variations in MHE and their associations with ALFF. METHODS: Blood zinc levels were compared in 150 patients with cirrhosis. Among them, 49 underwent rs-fMRI to evaluate associations between zinc levels and ALFF, after adjusting for confounders. RESULTS: Blood zinc levels were significantly lower in patients with MHE than in those with no hepatic encephalopathy (4.63 vs. 5.06 mg/L; P = 0.022). MHE prevalence was higher in females than in males (35.2% vs. 19.0%; P = 0.025). ALFFs in the bilateral angular gyrus and precuneus were positively correlated with blood zinc levels, whereas those in the bilateral fusiform gyrus were negatively correlated (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Low blood zinc levels in patients with MHE are associated with altered neural activity in the bilateral angular gyrus, precuneus, and bilateral fusiform gyrus, representing a neural basis for cognitive impairment in MHE.