Hepatic encephalopathy: diagnosis

In clinical practice, it is important to distinguish between hepatic encephalopathy, which develops in acute and chronic liver diseases. In general, the symptomatology is similar, but with acute liver damage 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 disorders of cerebral circulation, uremic, chloropenic, alcoholic and other coma. Usually, there are no major differential diagnostic difficulties, as patients with hepatic encephalopathy usually have jaundice, liver odor from the mouth, appropriate indications in the history of liver disease, toxic hepatotropic effects. It is also necessary to take into account the results of laboratory studies.

With the use of a salt-free diet, diuretics and abdominal paracentesis, patients with cirrhosis may develop hyponatremia. At the same time there is apathy, headache, nausea, arterial hypotension. The diagnosis is confirmed when a low level of sodium in the serum is detected and the urea concentration is increased. Such a condition can be combined with an impending hepatic coma.

Acute alcoholic kurtosis is a particularly complex diagnostic problem, as it can be combined with hepatic encephalopathy. Many syndromes, characteristic of alcoholism, can be caused by portosystemic encephalopathy. Alcoholic delirium (dellirium tremens) differs from hepatic encephalopathy with prolonged motor excitation, increased activity of the autonomic nervous system, insomnia, intimidating hallucinations and a smaller and faster tremor. In patients, face hyperemia, agitation, superficial and formal answers to questions are noted. Tremor disappearing during rest, becomes rough and irregular during periods of activity. Often observed pronounced anorexia, often accompanied by calls for vomiting and vomiting.

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

Encephalopathy Wernicke is often observed with severe malnutrition and alcoholism.

Hepatolenticular degeneration (Wilson's disease) occurs in young patients. The disease is often of a family nature. With this pathology there is no fluctuation in the severity of symptoms, choreoathetoid hyperkinesis is more common than a "clapping" tremor, the Kaiser-Fleischer ring is determined around the cornea and, as a rule, it is possible to detect a violation of copper metabolism.

Latently occurring functional psychoses - depression or paranoia - often appear against the background of an impending hepatic coma. The nature of developed mental disorders depends on the preceding characteristics of the personality and is associated with the enhancement of its characteristic features. The severity of serious mental disorders in these patients often leads to their hospitalization in a psychiatric hospital. Chronic mental disorders may not be associated with impaired liver function in patients with diagnosed hepatic disease. In order to prove the presence of chronic hepatic encephalopathy, diagnostic studies are conducted: phlebography or CT with intravenous radiocontrast, which allows to reveal the expressed collateral circulation. It may be useful to evaluate the clinical symptoms and changes in the EEG with increasing or decreasing the amount of protein in the food.

Laboratory data

• The general analysis of the blood: neutrophilic leukocytosis, an increase in ESR, anemia and thrombocytopenia (especially pronounced with the development of hemorrhagic syndrome).
• The general analysis of urine: proteinuria, cylindruria, microhematuria, bilirubin, urobilin are determined.
• Biochemical blood test: hyperbilirubinemia (with acute hepatic encephalopathy, the level of bilirubin in the blood can exceed the norm by 5 times or more, reaching 300 μmol / l and more in some cases); a sharp increase in the activity of aminotransferases, especially alanine, organ-specific enzymes (ornithylcarbomoyltransferase, arginase, fructose-1-phosphate aldolase); a decrease in the activity of pseudocholinesterase; hypoalbuminemia; increase in the level of y-globulin; hypoprothrombinemia; hypocholesterolemia (a drop in cholesterol below 2.6 mmol / l is considered an indicator of a critical violation of liver function); reduction of the sulem test to 1.4-1.2 ml; increase in the level of ammonia (with encephalopathy in the background of cirrhosis of the liver and less often with acute liver damage); increased creatinine content; decrease in urea (however, with concomitant renal failure - an increase); tendency to hypoglycemia; high levels 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 increased content of aminotransferases and hepatic-specific enzymes.

Spinal fluid examination

The pressure of cerebrospinal fluid is normal, its transparency is not violated. Patients in the hepatic coma can detect an increase in protein concentration, but the number of cells is not changed. In some cases, there is an increase in the levels of glutamic acid and glutamine.

Electroencephalography

In hepatic encephalopathy, an electroencephalogram (EEG) reveals a bilateral-synchronous decrease in frequency and an increase in the amplitude of normal a-rhythm with a frequency of 8-13 in 1 s to a 5-rhythm with a frequency of less than 4 in 1 s. These data can be most accurately estimated using frequency analysis. Incentives that cause an activation reaction, such as opening the eyes, do not affect the main rhythm. Changes appear in the frontal and parietal areas and extend to the occipital.

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

With a prolonged course of chronic liver disease with permanent damage to neurons, oscillations on the EEG can be delayed or more frequent and flattened (so-called flat EEGs). Such changes can "fix up" and not disappear on the background of a diet.

Changes in the EEG are detected very early, even before the appearance of mental or biochemical disorders. They are non-specific and can also be found in conditions such as uremia, hypercapnia, vitamin B12 deficiency, or hypoglycaemia. In patients with liver disease and in a clear consciousness, the presence of such changes on the EEG is a reliable diagnostic feature.

Method of evoked potentials

The evoked potentials are electrical potentials obtained by stimulation of cortical and subcortical neurons with visual or auditory stimuli or with stimulation of somatosensory nerves. This method allows to evaluate the conductivity and functional state of the afferent pathways between stimulated peripheral nerve endings in the tissues and the cortex of the brain. Changes in auditory evoked potentials of the cerebral trunk (SVPMS), visual (PVP) and somatosensory (SSVP) evoked potentials are detected in patients with clinically expressed or subclinical encephalopathy. However, they have more research than clinical significance. Since the sensitivity of these methods varies from one study to another, VEP and SVMSS occupy little place in the definition of subclinical encephalopathy, especially when compared to psychometric tests. The value 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 initial stages of encephalopathy. It may be that such visual P-300 evoked potentials are more sensitive when subclinical hepatic encephalopathy is detected in patients with cirrhosis than psychometric tests.

Scanning of the brain

Computer and magnetic resonance imaging (CT and MRI, respectively) can detect atrophic changes in the brain, even in patients with well-compensated cirrhosis of the liver. These changes are caused by a serious impairment of liver function. Atrophy is especially pronounced in patients with persistently persistent chronic encephalopathy and is aggravated with alcoholism. With the help of CT it is possible to quantify the severity of cerebral edema and atrophy of the cortex, including in patients with subclinical portosystemic encephalopathy. The amplification of the signal from basal ganglia on T1-weighted images in patients with liver cirrhosis does not appear to be associated with encephalopathy, but correlates with the serum bilirubin and manganese concentration in the blood.

Morphological study

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

In a microscopic study, patients with liver cirrhosis and those who died from the hepatic coma have more characteristic changes in astrocytes than in neurons. The proliferation of astrocytes with an increase in nuclei, bulging nucleoli, marginalization of chromatin and accumulation of glycogen is revealed. Similar changes are characteristic for astrocytosis of the second type in Alzheimer's disease. They are found mainly in the cerebral cortex and in the basal ganglia and are associated with hyperammonemia. Damage to neurons is minimal. Probably, in the early stages of the change, astrocytes are reversible.

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

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

Experimental hepatic coma

In acute liver failure, an increase in the permeability of the blood-brain barrier with specific damage to its transport systems is observed. However, in rats with galactosamin-induced liver failure present in the precomatous state, there is no generalized increase in barrier permeability. With this, there are obvious difficulties in creating a model of a similar state in animals.

[1], [2], [3], [4], [5], [6]