New technologies – new insights into the pathogenesis of hepatic encephalopathy

Longitudinal neurometabolic changes in the hippocampus of a rat model of chronic hepatic encephalopathy

“…In support of this hypothesis, no significant changes in the Glu-Gln cycle between astrocytes and neurons were measured in a recent in vivo 13 C-MRS study performed in the same animal model. 73 The decline in Glu concentration may in turn induce the decrease in Asp, since the 2 metabolites are linked by transamination. Although not measurable by 1 H-MRS, this finding also raises the question of whether this change influences alpha-ketoglutarate.…”

Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy

“…The diverse neurological manifestations of CLD present a diagnostic challenge for modern hepatologists, with magnetic resonance techniques representing a highly profitable avenue to investigate structural and functional aspects of brain dysfunction in an objective way (Table 2). 151,152 While there is widespread acceptance of its importance, there is little consensus on how best to diagnose and monitor HE. Of note, modern clinical MRI scanners with multinuclear MR spectroscopy capabilities and brain mapping software can objectively demonstrate structural and functional cellular changes (such as brain size and astrocyte swelling) using volumetric MRI, magnetization transfer MRI, diffusion-weighting MRI, functional MRI with oxygenation measurements and in vivo 1 H and 31 P MR spectroscopy, with the option of performing many sequences at a single sitting to maximise information gathering and cohort characterisation.…”

“…[153][154][155][156][157][158] PET studies have provided clear evidence of increased ammonia uptake in the brain and alterations in regional cerebral blood flow, as well as evidence of neuroinflammation, microglial activation and altered benzodiazepine receptors, confirming the role of these putative mechanisms in the pathogenesis of HE. 152,156 Investigations using MRI have shown evidence of hyperintensity of the basal ganglia, possibly related to the deposition of manganese, which correlated with the severity of extrapyramidal symptoms. 154 Other studies showed altered magnetization transfer ratio suggesting regional brain swelling, which in the early stages was also evident in the white matter.…”

The Neurobiology of Hepatic Encephalopathy

“…In cirrhotics, its serum concentration increases two to three times, an increase that is also exacerbated by the induction of glutaminase expression by enterocytes, which hydrolyzes the amino acid glutamine into glutamate and ammonia to obtain energy [9]. At least one haplotype of the glutaminase gene appears to be related to a higher propensity to develop clinically symptomatic encephalopathy, demonstrating that the constitutive activity of this enzyme undergoes genetic variations [13].…”