Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy

Douglass, A. E.; Mardini, Hanan Al; Record, C. O.

doi:10.1016/s0168-8278(01)00004-6

Cited by 40 publications

(28 citation statements)

References 23 publications

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“…The safety of administering an aa solution to patients with cirrhosis has been extensively studied 8,11,12 without any complication such as development of overt HE. Similar studies have used aa 13 and glutamine challenge [14][15][16] which produces ammoniagenesis and again no adverse effects were reported using this strategy.…”

Section: Ethical Considerationsmentioning

confidence: 63%

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Shawcross

Davies

Williams

et al. 2004

Journal of Hepatology

472

318

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Section: Ethical Considerationsmentioning

confidence: 63%

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Shawcross

Davies

Williams

et al. 2004

Journal of Hepatology

472

318

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“…10 Similarly, they showed that the administration of an amino acid solution similar in composition to ours was also followed by deterioration in neuropsychological test results. 39 We cannot explain the differences in these observations but suggest that differences may be due to different populations under study and bias due to the lack of a blinded control group.…”

Section: Discussionmentioning

confidence: 85%

Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis

et al. 2003

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Hyperammonemia is a universal finding after gastrointestinal hemorrhage in cirrhosis. We administered an oral amino acid solution mimicking the hemoglobin molecule to examine neuropsychological changes, brain glutamine levels, and brain magnetization transfer ratio (MTR). Forty-eight metabolically stable patients with cirrhosis and no evidence of "overt" hepatic encephalopathy (HE) were randomized to receive 75 g of amino acid solution or placebo; measurements were performed before and 4 hours after administration. Neuropsychological tests included the Trails B Test, Digit Symbol Substitution Test, memory subtest of the Randt battery, and reaction time. Plasma was collected for ammonia and amino acid measurements, and brain metabolism was studied using proton magnetic resonance (MR) spectroscopy in the first 16 randomized patients. In 7 other patients, MTR was measured. A significant increase in ammonia levels was observed in the amino acid group (amino acid group, 76 ؎ 7.3 to 121 ؎ 6.4 mol/L; placebo, 83 ؎ 3.3 to 78 ؎ 2.9 mol/L; P < .001). Neuropsychological function improved significantly in the placebo group, but no significant change in neuropsychological function was observed in the amino acid group. Brain glutamate/glutamine (Glx)/creatine (Cr) ratio increased significantly in the amino acid group. MTR decreased significantly from 30 ؎2.9 to 23 ؎ 4 (P < .01) after administration of the amino acid solution. In conclusion, an improvement in neuropsychological test results followed placebo, which was not observed in patients administered the amino acid solution. Induced hyperammonemia resulted in an increase in brain Glx/Cr ratio and a decrease in MTR, which may indicate an increase in brain water as the operative mechanism. A mmonia is believed to be central in the pathogenesis of hepatic encephalopathy (HE). [1][2][3][4] It is well known that upper gastrointestinal bleeding in cirrhotic patients produces hyperammonemia and precipitates HE. [1][2][3][4][5][6] Simulating the metabolic effects of upper gastrointestinal bleeding by oral administration of erythrocytes has been shown to induce hyperammonemia and behavioral disturbance in portacaval-shunted rats. 7 In an uncontrolled study, we showed that oral administration of an amino acid solution that is identical to the amino acid profile of hemoglobin results in deterioration in memory test results, suggesting that this may be a clinically valid model to study the pathogenesis of HE. 8 Although the data relating arterial ammonia concentration to the severity of HE are controversial, there is growing evidence that greater arterial ammonia concentrations are observed in more severe states of HE. 3,4,9 In a recent study in patients with acute liver failure, an arterial concentration of ammonia greater

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“…Since gastrointestinal bleeding is a known precipitant of HE, we have also used an amino acid mixture resembling the composition of haemoglobin and have shown that EEG slowing correlated with the dose of amino acid administered [29], while competition for cerebral uptake between branch chain and aromatic amino acids is of little importance in the development of induced EEG abnormalities [30]. In the present study, we used a mixture of serine, threonine, and glycine in order to maximise the hyperammonaemia from each gram of amino acid administered [19].…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia

Mardini

Smith

Record

et al. 2011

Journal of Hepatology

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Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy

Cited by 40 publications

References 23 publications

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis

Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia

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