Liver encephalopathy - Diagnosis

In clinical practice, it is important to distinguish between hepatic encephalopathy developing in acute and chronic liver diseases. In general, the symptoms are similar, but in acute liver lesions, all manifestations of hepatic encephalopathy progress much faster than in chronic ones.

Most often it is necessary to differentiate hepatic encephalopathy and hepatic coma from cerebrovascular accidents, uremic, chloropenic, alcoholic and other comas. Usually there are no major differential diagnostic difficulties, since patients with hepatic encephalopathy, as a rule, have jaundice, liver odor from the mouth, corresponding indications in the anamnesis of liver diseases, toxic hepatotropic effects. It is also necessary to take into account the results of laboratory studies.

When using a salt-free diet, diuretics and abdominal paracentesis in patients with liver cirrhosis, hyponatremia may develop. This is accompanied by apathy, headache, nausea, and arterial hypotension. The diagnosis is confirmed by detecting a low sodium level and an increase in the urea concentration in the blood serum. This condition may be combined with impending hepatic coma.

Acute alcoholic excess is a particularly difficult diagnostic problem, as it may be combined with hepatic encephalopathy. Many syndromes characteristic of alcoholism may be caused by portosystemic encephalopathy. Alcoholic delirium (dellirium tremens) differs from hepatic encephalopathy by prolonged motor agitation, increased activity of the autonomic nervous system, insomnia, frightening hallucinations, and a finer and faster tremor. Patients have facial hyperemia, agitation, and superficial and formal answers to questions. The tremor, which disappears during rest, becomes coarse and irregular during periods of activity. Severe anorexia is often observed, often accompanied by retching and vomiting.

Portosystemic encephalopathy in patients with alcoholism has the same characteristic signs as in other patients, but they rarely have muscle rigidity, hyperreflexia, clonus of the feet due to concomitant peripheral neuritis. The differential diagnosis uses EEG data and the dynamics of clinical signs during the use of a protein-free diet, lactulose and neomycin.

Wernicke's encephalopathy is often seen in association with severe malnutrition and alcoholism.

Hepatolenticular degeneration (Wilson's disease) occurs in young patients. The disease often has a familial nature. In this pathology, there is no fluctuation in the severity of symptoms, choreoathetoid hyperkinesis is more characteristic than "flapping" tremor, the Kayser-Fleischer ring is determined around the cornea and, as a rule, a disorder of copper metabolism can be detected.

Latent functional psychoses - depression or paranoia - often manifest against the background of an impending hepatic coma. The nature of the mental disorders that develop depends on the previous personality traits and is associated with the intensification of their characteristic features. The severity of serious mental disorders in such patients often leads to their hospitalization in a psychiatric hospital. Chronic mental disorders may not be associated with liver dysfunction in patients with diagnosed liver disease. In order to prove the presence of chronic hepatic encephalopathy, diagnostic studies are carried out: phlebography or CT with intravenous administration of a radiopaque substance, which allows us to identify pronounced collateral circulation. An assessment of clinical symptoms and EEG changes with an increase or decrease in the amount of protein in food may be useful.

Laboratory data

• Complete blood count: neutrophilic leukocytosis, increased ESR, anemia and thrombocytopenia (especially pronounced with the development of hemorrhagic syndrome).
• General urine analysis: proteinuria, cylindruria, microhematuria, bilirubin, urobilin are determined.
• Blood biochemistry: hyperbilirubinemia (in acute liver encephalopathy, the bilirubin level in the blood may exceed the norm by 5 times or more, in some cases reaching 300 μmol/l or more); a sharp increase in the activity of aminotransferases, especially alanine, organ-specific enzymes (ornitholcarbamoyltransferase, arginase, fructose-1-phosphate aldolase); a decrease in the activity of pseudocholinesterase; hypoalbuminemia; an increase in the level of y-globulins; hypoprothrombinemia; hypocholesterolemia (a drop in cholesterol below 2.6 mmol/l is considered an indicator of critical liver dysfunction); a decrease in the sublimate test to 1.4-1.2 ml; an increase in the ammonia level (in encephalopathy against the background of liver cirrhosis and less often in acute liver damage); an increase in the creatinine content; decreased urea content (however, with concomitant renal failure - an increase); tendency to hypoglycemia; high level of bile acids; hypokalemia; hyponatremia. In the terminal stage of hepatic encephalopathy, bilirubin-enzyme dissociation may develop, i.e. an increase in the level of total bilirubin and a decrease in the previously elevated content of aminotransferases and liver-specific enzymes.

Cerebrospinal fluid examination

The cerebrospinal fluid pressure is normal, its transparency is not impaired. In patients with hepatic coma, an increase in protein concentration can be detected, but the number of cells is unchanged. In some cases, an increase in the level of glutamic acid and glutamine is observed.

Electroencephalography

In hepatic encephalopathy, the electroencephalogram (EEG) reveals a bilaterally synchronous decrease in frequency and increase in amplitude of the normal a-rhythm with a frequency of 8-13 per sec to the 5-rhythm with a frequency of less than 4 per sec. These data can be most accurately assessed using frequency analysis. Stimuli that cause an activation reaction, such as opening the eyes, do not affect the basic rhythm. Changes appear in the frontal and parietal areas and spread to the occipital areas.

This method helps in the diagnosis of hepatic encephalopathy and evaluation of treatment results.

In long-term chronic liver disease with permanent damage to neurons, EEG oscillations may be slow or rapid and flattened (so-called flat EEG). Such changes may become “fixed” and not disappear with diet.

Changes in the EEG are detected very early, even before the onset of mental or biochemical disorders. They are nonspecific and can also be detected in conditions such as uremia, hypercapnia, vitamin B12 deficiency or hypoglycemia. In patients suffering from liver disease and in clear consciousness, the presence of such changes in the EEG is a reliable diagnostic sign.

Evoked potential method

Evoked potentials are electrical potentials obtained by stimulating cortical and subcortical neurons with visual or auditory stimuli or by stimulating somatosensory nerves. This method allows to evaluate the conductivity and functional state of afferent pathways between stimulated peripheral nerve endings in tissues and the cerebral cortex. In patients with clinically evident or subclinical encephalopathy, changes in auditory evoked potentials of the brainstem (ABE), visual (VEP) and somatosensory (SSEP) evoked potentials are detected. However, they have more research than clinical significance. Since the sensitivity of these methods varies from one study to another, VEP and ABE occupy a minor place in the definition of subclinical encephalopathy, especially in comparison with psychometric tests. The significance of SSEP requires further study.

A new method of recording endogenous potentials associated with a reaction to an event is currently being studied. It requires interaction with the patient, so the use of such a study is limited to the early stages of encephalopathy. It may turn out that such visual P-300 evoked potentials are more sensitive in detecting subclinical hepatic encephalopathy in patients with liver cirrhosis than psychometric tests.

Brain scan

Computer tomography and magnetic resonance imaging (CT and MRI, respectively) can detect atrophic changes in the brain even in patients with well-compensated liver cirrhosis. These changes are due to severe liver dysfunction. Atrophy is especially pronounced in patients with long-term persistent chronic encephalopathy and is aggravated by alcoholism. CT can quantitatively assess the severity of cerebral edema and cortical atrophy, including in patients with subclinical portosystemic encephalopathy. Increased signal from the basal ganglia on T1-weighted images in patients with liver cirrhosis is apparently not associated with encephalopathy, but correlates with the concentration of serum bilirubin and manganese in the blood.

Morphological study

Macroscopically, the brain may not be changed, but in about half of the cases, cerebral edema is detected. This is especially characteristic of young patients who died after a prolonged deep coma.

Microscopic examination of patients with liver cirrhosis who died of hepatic coma reveals more characteristic changes in astrocytes than in neurons. Astrocyte proliferation with enlarged nuclei, protruding nucleoli, chromatin margination, and glycogen accumulation is revealed. Such changes are characteristic of type 2 astrocytosis in Alzheimer's disease. They are found mainly in the cerebral cortex and basal ganglia and are associated with hyperammonemia. Neuronal damage is minimal. Probably, at early stages, astrocyte changes are reversible.

With a long course of the disease, structural changes may become irreversible and treatment is ineffective, chronic hepatocerebral degeneration develops. In addition to changes in astrocytes, thinning of the cerebral cortex is observed with a decrease in the number of neurons in the cortex, basal ganglia and cerebellum.

Demyelination of the pyramidal tract fibers is accompanied by the development of spastic paraplegia.

Experimental hepatic coma

In acute liver failure, there is an increase in the permeability of the blood-brain barrier with specific damage to its transport systems. However, in rats with galactosamine-induced liver failure, which are in a precomatose state, there is no generalized increase in barrier permeability. This is associated with obvious difficulties in creating a model of a similar condition in animals.

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