Cristina Dondi

Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance

Neuropsychological status, as assessed by trailmaking test; plasma amino acids, and ammonia, were studied in 54 cirrhotics without clinical evidence of encephalopathy to determine the prevalence of subclinical mental dysfunction and its relationship to metabolic abnormalities. Control values for psychometric performance were established in 54 normal subjects matched for age, sex, educational level, and employment status. Of these subjects, 16 were also used as controls for fasting ammonia and plasma amino acids. Eighteen cirrhotics (33%) showed impaired performances of the psychometric test; free tryptophan and the ratio free tryptophan to neutral amino acids were increased in 37% and 62% of cases and correlated with the psychometric scores (r=0.45 andr=0.70, respectively). In eight cirrhotics with mild encephalopathy, psychometric and metabolic evaluations were repeated several times during the infusion of amino acid solutions rich in branched-chain amino acids. Again significant correlations were observed between the psychometric scores and plasma amino acids. We conclude that a considerable proportion of clinically normal cirrhotics have neuropsychological deficits. The severity of impairment may be related to the plasma amino acid imbalance, namely to an increased passage of tryptophan across the blood-brain barrier.

Splanchnic vein measurements in patients with liver cirrhosis: a case-control study.

The portal venous system was evaluated by real‐time ultrasonography in 100 consecutive cirrhotic patients and 100 pair‐matched controls to assess the sensitivity and specificity of ultrasound findings in detecting or excluding cirrhosis. The best discriminant findings were the expiration diameters of the superior mesenteric and the splenic vein and, chiefly, their sum corrected by body surface. In cirrhotics the calibers of the splanchnic veins significantly increase in relation to the extent of esophageal varices, but in individual patients this increase cannot predict the extent of varices, which are the main determinant of the bleeding risk.

Degeneration of the corticospinal tract following portosystelnic shunt associated with spinal cord infarction

The clinicopathological aspects of a case of myelopathy that followed the creation of a surgical porto-caval shunt for hepatic cirrhosis and oesophageal varices are presented. Degeneration of the lateral corticospinal tracts associated with diffuse bilateral ischaemic changes of the spinal gray matter and proliferation of Alzheimer type 2 glia in the brain and brain stem were the most prominent findings. The association of corticospinal tract degeneration and ischaemic lesions of spinal gray matter in absence of any anatomical cause of spinal cord infarction suggests that a modification of the spinal blood flow caused by creation of portosystemic shunts might be the basic pathogenetic mechanism of this complication of severe liver disease

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis.

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r=0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ratio of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.

Plasma Amino Acids as Markers of Liver Dysfunction in Cirrhotics

To determine the role of liver dysfunction in the plasma amino acid profile of cirrhotic patients, we correlated basal plasma amino acids and several biochemical and functional hepatic variables in 29 cirrhotics with normal mental state or mild encephalopathy. Increased levels of aromatic amino acids and free tryptophan correlated positively with the extent of portosystemic shunt, as assessed by the ammonia tolerance test (r = 0.758 and r = 0.589, respectively). There was a negative correlation between these amino acids and liver function, as evaluated by the galactose elimination capacity test (r = -0.657 and r = -0.551), thus suggesting that phenylalanine, tyrosine, and free tryptophan may be considered indexes of liver dysfunction in non-comatose cirrhotics.

The Role of Muscle Protein Catabolism in the Plasma Amino Acid Profile of Cirrhotics

Patients with liver cirrhosis have peculiar abnormalities in plasma amino acid concentrations: increased aromatic amino acids, methionine and free tryptophan, and decreased branched-chain amino acids.1,2 Increased breakdown of lean body mass was suggested as a mechanism by which aromatic amino acids may accumulate in the general circulation.3 A complete evaluation of myofibrillar protein degradation may be achieved by simultaneous assessment of daily 3-methylhistidine and creatinine in urine.4 In previous studies an increased myofibrillar protein catabolic rate was demonstrated in patients with liver cirrhosis with and without muscle wasting.5

Proteins and Amino Acids in Liver Failure

Patients with liver cirrhosis scarcely tolerate protein thus large nitrogen loads are likely to induce hepatic coma. A protein load, either as a protein rich meal or a gastrointestinal bleeding, which increase nitrogen reabsorption, or an intravenous administration of protein hydrolisates, may produce stupor and drowsiness up to deep coma, at the same time increasing blood ammonia. This clinical observation forms the basis of the ‘ammonia’ theory of hepatic encephalopathy.