Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy

et al. 2022

Front. Hum. Neurosci.

BackgroundPrevious studies on voxel-based morphometry (VBM) have found that there were gray matter alterations in patients with hepatic encephalopathy (HE). However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE.MethodsThe studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping (SDM) method was applied to quantitatively estimate the regional gray matter abnormalities in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration.ResultsThere were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume (GMV) in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum.ConclusionGray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE.

Section: Discussionsupporting

confidence: 92%

Brain Gray Matter Alterations in Hepatic Encephalopathy: A Voxel-Based Meta-Analysis of Whole-Brain Studies

Zhu

Zhang

et al. 2022

Front. Hum. Neurosci.

“…These results suggest that whole-brain dynamic functional connectivity undergoes a progressive disruption in patients with HBV-RC. Progressive impairment of the static network system in HBV-RC patients has been widely verified, 8,9 and our results extend those findings to dynamic network integration.…”

Section: Discussionsupporting

confidence: 85%

“…4 Weaker FC has been detected within multiple brain networks related to MHE, which include the visual network (VIS), default mode network (DMN), salience network, central executive network, and thalamocortical circuits, 5,6 and impairment of network connectivity in the whole brain has also been reported. 7 Alteration of FC in the NHME stage 8 and the progressive deterioration of FC along with progression from NHME to MHE have also detected in patients with HBV-RC. [9][10][11] However, these studies evaluated brain activity averaged over the entire scanning period and, thus, the results [9][10][11] do not reflect the highly dynamic organization of the brain which exhibits time-varying neural activity and quickly changing neural integration.…”

mentioning

confidence: 92%

Progressive Disruption of Dynamic Functional Network Connectivity in Patients With Hepatitis B Virus‐related cirrhosis

Lin

Magnetic Resonance Imaging

et al. 2021

Background: The diseased-related dynamic functional network connectivity (dFNC) disruption and its relationship with cognitive impairment in hepatitis B virus-related cirrhosis (HBV-RC) patients with minimal hepatic encephalopathy (MHE) and no MHE (NMHE) remain unknown. This knowledge would help identify MHE pathophysiology and monitor disease progression in HBV-RC patients. Purpose: To investigate the dFNC in patients with NMHE and MHE and the relationship between dFNC indices with the psychometric hepatic encephalopathy score (PHES). Study type: Prospective. Population: Thirty HBV-RC patients (including 17 NMHE and 13 MHE) and 38 healthy controls (HC). Field strength/sequence: A 1.5 T MRI and gradient-echo echo-planar imaging and fast field echo three-dimensional T1weighted imaging. Assessment: The independent components, dFNC matrix and dFNC indices (mean dwell times [DT], number of states, number of transitions, and fraction time in each state), were obtained through GIFT package. Cognitive measurement and patients grouping were based on PHES tests. Statistical Tests: One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, spearman's correlation analysis and the false discovery rate. Significance level: P < 0.05. Results: Compared to HC (21.1 AE 4.02), the DT of state 1 decreased in NMHE (9.0 AE 3.04, P = 0.062, 95% confidence interval [CI] is À0.65 to 24.88) and significantly in MHE stage (1.2 AE 1.01) and was significantly correlated with PHES (r = 0.5) for all patients. The DT of state 2 increased gradually in NMHE (75.2 AE 13.10, P = 0.052, 95% CI, À54.23 to 0.28) and significantly in MHE stage (94.6 AE 15.61) when compared to HC (48.2 AE 6.97). Moreover, the connectivity between cognitive control network (CCN) and visual network (VIS) in state 1 (0.7 AE 0.79) and between default mode (DMN) and VIS in state 2 (À0.2 AE 0.29) decreased significantly in MHE when compared to HC (0.1 AE 0.68 for CCN-VIS in state 1 and 0.1 AE 0.17 for DMN-VIS for state 2). Data Conclusion: dFNC exhibited progressive impairment as the disease advances in patients with HBV-RC.

“…Hippocampal volume is decreased in cirrhosis patients. Neuroinflammation affects the expression of hippocampal glutamate receptors and GABAergic tone in the cerebellum, inducing spatial memory or movement disorder (Hassan et al, 2019;Lin et al, 2019).…”

Section: Neuroinflammation and Immune Regulationmentioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Front. Cell. Infect. Microbiol.

Ruan

et al. 2021

Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.