Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge, Dominic R.; Tranah, Edward J.; Shawcross, Debbie L.

doi:10.1016/j.jceh.2014.06.004

Cited by 235 publications

(209 citation statements)

References 124 publications

(128 reference statements)

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“…Previous studies have shown that systemic levels of ammonia in MHE do not correlate with the severity of liver disease and the presence of MHE [22,23]. Contrary to that, there is a positive correlation of ammonia blood levels with the stage of HE in overt HE [24].…”

Section: Discussionmentioning

confidence: 72%

Prevalence of Helicobacter pylori Infection in Patients with Minimal Hepatic Encephalopathy

Schulz

Schütte

Reisener

et al. 2016

JGLD

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Background: Ammonia is a critical factor in the pathogenesis of minimal hepatic encephalopathy (MHE). Most of the ammonia is from bacterial production in the intestinal tract. Non-absorbable antibiotics and non-absorbable disaccharides are therefore the therapy of choice. A few studies have addressed the effect of ammonia produced by H. pylori in the pathogenesis of MHE. Methods: In this prospective clinical trial, 84 consecutive patients with liver cirrhosis (LC) underwent laboratory, psychometric und neurophysiological testing to determine serological H. pylori status, MHE and blood ammonia levels. Relevant clinical and demographic characteristics were documented. Results: Out of 84 LC patients (83% male), 29% presented with MHE as assessed by critical flicker frequency analysis (CFF). The prevalence of H. pylori infection in the cohort was 21%; 22% of H. pylori-infected patients presented with MHE according to the criterion of a positive CFF result. If the criterion for MHE was a positive CFF and a positive NCT-A result, then 17% of H. pylori positive patients suffered from MHE. The prevalence of MHE in H. pylori-negative patients, based on CFF alone and on the combination, was 30%. A proportion of 19% of the patients with MHE had increased blood ammonia levels. Conclusion: The amount of ammonia produced by H. pylori does not affect venous ammonia levels. Therefore, an additional benefit of H. pylori eradication in the treatment of hepatic encephalopathy in patients with LC is unlikely to occur. Key words: – – – – – . Abbreviations: CFF: critical flicker frequency analysis; GCP: good clinical practice; GI : gastrointestinal; HE: hepatic encephalopathy; H. pylori: Helicobacter pylori; LC: liver cirrhosis; MHE: minimal hepatic encephalopathy; NASH: non-alcoholic steatohepatitis; NCT-A: number connection test-A; NCT-B: number connection test-B; PHES: Psychometric hepatic encephalopathy score.

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Section: Discussionmentioning

confidence: 72%

Prevalence of Helicobacter pylori Infection in Patients with Minimal Hepatic Encephalopathy

Schulz

Schütte

Reisener

et al. 2016

JGLD

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“…GS is found in the hepatocytes surrounding the hepatic veins, muscle cells and astrocytes. 1,2 Within the CNS, GS is located exclusively within the astrocytes. Thus, these cells bear the brunt of the toxic effects of ammonia, in turn leaving the neurons completely unaffected by the exposure.…”

Section: Correct Answers: B C and Ementioning

confidence: 99%

“…These changes may also be seen in patients with urea cycle defects and experimental models of hyperammonemia. 2,6,7 Within the astrocytes, ammonia combines with glutamate to form glutamine. This leads to reduced levels of glutamate in the cell, a deficiency that is partly compensated by conversion of a-ketoglutarate to glutamate.…”

Section: Correct Answers: B C and Ementioning

confidence: 99%

“…This may be due to earlier recognition of the severity of the disease, leading to better medical care and use of salvage emergency transplant. 2,13,14 The brain lacks an effective urea cycle, thus leaving the removal of ammonia exclusively to the glutamate synthetase in the astrocytes. In ALF, the brain edema is primarily cytotoxic in nature, resulting from astrocyte swelling.…”

Section: Correct Answers: D and Ementioning

confidence: 99%

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Hepatobiliary Quiz (Answers)—15 (2015)

Rathi

Dhiman

2015

Journal of Clinical and Experimental Hepatology

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“…It was shown that vasogenic edema in AHE is likely caused by infectious complications of ALF in the form of spontaneous peritonitis caused by translocation of bacterial intestinal flora, SIRS or septicemia. Under these conditions, the level of bacterial endotoxins (LPS), that are considered a classic factor of BBB integrity damage [64], will increase in blood.…”

Section: Introductionmentioning

confidence: 99%

Modern view on hepatic encephalopathy: basic terms and concepts of pathogenesis

Shulyatnikova

Shavrin

2017

Patologìâ

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Background. The problem of acute and chronic forms of hepatic encephalopathy (HE) is not clearly identified among modern problems of hepatology and neuroscience in Ukraine. Despite the significant contribution to the development of lethal complications in patients with liver pathology and long history of the study of this issue, there is still no unified opinion on the links of HE pathogenesis.The aim of this review is to conduct a comprehensive analysis of current data on the spreading and mechanisms of development of HE.HE is a complex of potentially reversible neurocognitive disorders in patients with chronic or acute hepatic failure (ALF). HE is more often a complication of liver cirrhosis and is the second most frequent cause of hospitalization of such patients after ascites. When decompensating liver failure in acute or chronic hepatic pathology in patients severe forms of HE develop, accompanied by a progressive increase in intracranial pressure and the development of coma, which often ends lethal due to poor corrigibility of intracranial hypertension while maintaining hepatogenic neurointoxication. HE is considered as the end result of the accumulation of a number of neurotoxic substances in the brain, among which are ammonia, mercaptans, short chain fatty acids, false neurotransmitters, gamma-aminobutyric acid, manganese. The most popular among the reasons for the development of HE is the neurotoxic theory of ammonia. Ammonia is subjected to detoxification in the liver, turning into urea, a smaller fraction with the participation of glutamine synthetase is used in the synthesis of glutamine in muscles, liver and astrocytes of brain. In case of hepatic dysfunction and/or portosystemic shunting, the concentration of ammonia in blood increases up to 10 times and the main load for its detoxification is shifted to myocytes and astroglia. In ALF glutamine overload of astrocytes occurs with a change in intracellular osmolarity and subsequent edema of astroglia, which is accompanied by the development of cytotoxic edema of the brain. In this case, in astrocytes damaging of mitochondrial respiratory chain occurs and mitochondrial insufficiency develops, as well as processes of nitrosative-oxidative stress and oxidation of astrocytic and neuronal RNA, disruption of gene expression, synthesis of neuro-and gliotransmitters and synaptic plasticity. The increased influx of aromatic amino acids into brain leads to the synthesis of false neurotransmitters, which worsens serotoninergic, GABA-ergic, dopaminergic and glutamatergic neurotransmission. Damage to the components of the blood-brain barrier leads to aggravation of the water imbalance, penetration of hematogenous cytokines, endotoxins and other products of systemic inflammatory reaction into the cerebral parenchyma and development of neuroinflammation, which makes an important contribution to the further progression of cerebral edema.Conclusions: despite a comprehensive study of the problem, many open questions remain in the pathogenesis of HE. Special attention ...

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Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Cited by 235 publications

References 124 publications

Prevalence of Helicobacter pylori Infection in Patients with Minimal Hepatic Encephalopathy

Prevalence of Helicobacter pylori Infection in Patients with Minimal Hepatic Encephalopathy

Hepatobiliary Quiz (Answers)—15 (2015)

Modern view on hepatic encephalopathy: basic terms and concepts of pathogenesis

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