Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy

Rose, Christopher F.; Amodio, Piero; Bajaj, Jasmohan S.; Dhiman, Radha K.; Montagnese, Sara; Taylor-Robinson, Simon D; Vilstrup, Hendrik; Jalan, Rajiv

doi:10.1016/j.jhep.2020.07.013

Cited by 270 publications

(268 citation statements)

References 253 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…Ammonia is a neurotoxic molecule that readily crosses the BBB and is central in the pathogenesis of HE [26]. However, the pathogenesis of HE is complex and whilst ammonia holds an irrefutable, key role, it is not solely responsible for the neurocognitive dysfunction [29]. Many studies clearly demonstrate that the cognitive manifestations of hyperammonemia can be exacerbated in an inflammatory environment [79][80][81]; it has been proposed that hyperammonemia is the key that "unlocks" the BBB, making the brain susceptible to systemic inflammatory responses [82].…”

Section: Metabolic Liver Dysfunction and Ammoniamentioning

confidence: 99%

“…Adding to these features, NAFLD exhibits disruption of the gut microbiota and impairment of urea synthesis in the liver, leading to ammonia accumulation even in precirrhotic stages [24,25]. These disturbances, compounded by systemic inflammation, are central elements of the gut-liver-brain axis and acknowledged as significant in the pathogenesis of hepatic encephalopathy (HE), the neuropsychiatric syndrome associated with progressive liver injury [26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Kjærgaard

Mikkelsen

Wernberg

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

show abstract

Section: Metabolic Liver Dysfunction and Ammoniamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Kjærgaard

Mikkelsen

Wernberg

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…the formation of connections between the portal and the systemic circulation because of increased pressure in the portal system) and reaching the systemic circulation and the brain (Rose et al. 2020). HE is classified as a metabolic encephalopathy (i.e.…”

Section: The Astrocyte Circadian Clock In a Model Disorder: Hepatic Ementioning

confidence: 99%

The role of astrocytes in generating circadian rhythmicity in health and disease

Costa

2021

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

Evidence is accumulating that the mammalian circadian clock system is considerably more complex than previously believed, also in terms of the cell types that actually contribute to generating the oscillation within the master clock, in the suprachiasmatic nuclei of the hypothalamus. Here we review the evidence that has lead to the identification of a bona fide astrocytic circadian clock, and that of the potential contribution of such clock to the generation of circadian and seasonal rhythmicity in health and in neurodegenerative disorders. Finally, we speculate on the role of the astrocytic clock in determining some of the clinical features of hepatic encephalopathy, a reversible neuropsychiatric syndrome associated with advanced liver disease, which is characterized by transient, profound morphological and functional astrocytic abnormalities, in the absence of significant, structural neuronal changes.

show abstract

“…No studies exist on the prevalence of cerebral dysfunction linked to subclinical UE in individuals with kidney disease. Minimal hepatic encephalopathy (mHE) occurs in 30-85% of patients with liver cirrhosis [11][12][13] and has been associated with a higher risk of car accidents, impact on the quality of life, and legal implications [10,14]. Two tools have been validated for diagnosing mHE: the Psychometric Hepatic Encephalopathy Score (PHES) [15,16] the Critical flicker frequency (CFF) [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests

et al. 2021

View full text Add to dashboard Cite

Background: Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). Objective: To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. Methods: This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: 39 Hz for CFF and < À4 for PHES. All participants were also screened for cognitive function and depression. Results: Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. Conclusions: It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

show abstract

Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy

Cited by 270 publications

References 253 publications

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

The role of astrocytes in generating circadian rhythmicity in health and disease

Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests

Contact Info

Product

Resources

About