Liver Encephalopathy - Causes

Acute liver diseases and lesions.

1. Acute viral hepatitis A, B, C, D, E, G.
2. Acute viral hepatitis caused by herpes viruses, infectious mononucleosis, Coxsackie, measles, cytomegalovirus.
3. Icteric leptospirosis (Vasiliev-Weil disease).
4. Liver damage due to rickettsiosis, mycoplasma, fungal infections (in severe cases with generalized damage to all organs).
5. Septicemia with liver abscesses and purulent cholangitis.
6. Reye's syndrome is a liver disorder with the development of liver failure in children aged 6 weeks to 16 years 3-7 days after a viral upper respiratory tract infection.
7. Alcohol intoxication.
8. Drug-induced hepatitis.
9. Liver damage caused by industrial and production toxins, mixed toxins, aflatoxins.
10. Acute hepatic circulatory disorder (acute hepatic vein thrombosis).
11. Acute fatty liver of pregnancy (Sheehan's syndrome).
12. Heart failure.
13. Poisoning by poisonous mushrooms.

Chronic liver diseases.

1. Chronic hepatitis (with a high degree of activity).
2. Liver cirrhosis (late stages of the disease).
3. Hereditary disorders of bile acid metabolism (progressive intrahepatic cholestasis - Bieler's disease; hereditary lymphedema with recurrent cholestasis; cerebrohepatorenal syndrome; Zellweger syndrome).
4. Hemochromatosis.
5. Hepatolenticular degeneration (Wilson-Konovalov disease).

Malignant liver tumors.

Factors that provoke the development of hepatic encephalopathy include:

• consumption of alcohol and drugs that have a hepatotoxic and cerebrotoxic effect (hypnotics, sedatives, tuberculostatic, cytostatic, analgesic, etc.);
• anesthesia;
• surgical operations;
• formation of a portocaval anastomosis - in this case, ammonia and other cerebrotoxic substances enter from the intestines directly into the bloodstream, bypassing the liver;
• exogenous and endogenous infection - in this case, there is an increase in catabolic reactions, which leads to the accumulation of endogenous nitrogen, increased synthesis of ammonia; in addition, hyperthermia and hypoxia, which are manifestations of infection, contribute to intoxication;
• gastrointestinal bleeding - the spilled blood is a substrate for the formation of ammonia and other cerebrotoxins; in addition, hypovolemia, shock, hypoxia impair the nitrogen-excreting function of the kidneys and, thus, contribute to an increase in the content of ammonia in the blood;
• intake of excess protein with food, which is a substrate for the synthesis of ammonia and other cerebrotoxins;
• paracentesis with evacuation of a large amount of ascitic fluid - loss of electrolytes and proteins provokes and aggravates hepatic encephalopathy;
• excessive use of diuretics, profuse diuresis are accompanied by decreased blood circulation in vital organs, hypovolemia, hypokalemia, alkalosis, prerenal azotemia; spontaneous azotemia occurs due to increased enterohepatic circulation of urea;
• renal failure;
• metabolic alkalosis, in which the active diffusion of unionized ammonia across the blood-brain barrier increases;
• constipation - the synthesis and absorption of ammonia and other cerebrotoxins in the intestine increases due to the development of dysbacteriosis and digestive disorders;
• development of portal vein thrombosis in patients with liver cirrhosis, the addition of peritonitis, significant activation of the pathological process in the liver.

Other factors contributing to the development of encephalopathy

Patients with hepatic encephalopathy are extremely sensitive to sedatives, so their use should be avoided if possible. If the patient is suspected of having overdosed on such drugs, an appropriate antagonist should be administered. If the patient cannot be kept in bed and needs to be calmed, small doses of temazepam or oxazepam are prescribed. Morphine and paraldehyde are absolutely contraindicated. Chlordiazepoxide and hemineurin are recommended for patients suffering from alcoholism with impending hepatic coma. Patients with encephalopathy are contraindicated in drugs that are known to cause hepatic coma (e.g. amino acids and diuretics for oral use).

Potassium deficiency can be compensated for with fruit juices and effervescent or slowly dissolving potassium chloride. In emergency therapy, potassium chloride can be added to intravenous solutions.

Levodopa and bromocriptine

If portosystemic encephalopathy is associated with a disorder in dopaminergic structures, then replenishing dopamine reserves in the brain should improve the condition of patients. Dopamine does not pass through the blood-brain barrier, but its precursor, levodopa, can do so. In acute liver encephalopathy, this drug can have a temporary activating effect, but it is effective only in a small number of patients.

Bromocriptine is a specific dopamine receptor agonist with prolonged action. When given in addition to a low-protein diet and lactulose, it improves the clinical status and psychometric and electroencephalographic data in patients with chronic portosystemic encephalopathy. Bromocriptine may be a valuable drug for selected patients with poorly treatable chronic portal encephalopathy resistant to dietary protein restriction and lactulose, which has developed against the background of stable compensation of liver function.

Flumazenil

This drug is a benzodiazepine receptor antagonist and produces a temporary, variable, but clear improvement in approximately 70% of patients with hepatic encephalopathy associated with liver failure or cirrhosis. Randomized trials have confirmed this effect and have shown that flumazenil can interfere with the action of benzodiazepine receptor agonist ligands that are formed in situ in the brain in liver failure. The role of this group of drugs in clinical practice is currently under study.

Branched chain amino acids

The development of hepatic encephalopathy is accompanied by a change in the ratio between branched-chain amino acids and aromatic amino acids. Infusions of solutions containing a high concentration of branched-chain amino acids are used to treat acute and chronic hepatic encephalopathy. The results obtained are extremely contradictory. This is probably due to the use of different types of amino acid solutions in such studies, different routes of administration, and differences in patient groups. Analysis of controlled studies does not allow us to speak unequivocally about the effectiveness of intravenous administration of branched-chain amino acids in hepatic encephalopathy.

Given the high cost of intravenous amino acid solutions, it is difficult to justify their use in hepatic encephalopathy when blood levels of branched-chain amino acids are high.

Despite some studies showing that orally administered branched-chain amino acids are successful in treating hepatic encephalopathy, the effectiveness of this expensive treatment remains controversial.

Shunt occlusion

Surgical removal of the portocaval shunt may result in regression of severe portosystemic encephalopathy that developed after its placement. In order to avoid recurrent bleeding, the esophageal mucosa may be transected before performing this operation. Alternatively, the shunt may be closed using X-ray surgical techniques with the introduction of a balloon or steel coil. These techniques may also be used to close spontaneous splenorenal shunts.

Application of artificial liver

In patients with cirrhosis of the liver who are in a coma, complex treatments using an artificial liver are not used. These patients are either in a terminal state or come out of a coma without these methods. Treatment with an artificial liver is discussed in the section on acute liver failure.

Liver transplantation

This method may become a final solution to the problem of hepatic encephalopathy. One patient who suffered from encephalopathy for 3 years showed a marked improvement within 9 months after transplantation. Another patient with chronic hepatocerebral degeneration and spastic paraplegia showed a significant improvement after orthotopic liver transplantation.

Factors contributing to the development of acute hepatic encephalopathy in patients with liver cirrhosis

Electrolyte imbalances

• Diuretics
• Vomit
• Diarrhea

Bleeding

• Varicose veins of the esophagus and stomach
• Gastroduodenal ulcers
• Ruptures in Mallory-Weiss syndrome

Preparations

• Stopping drinking alcohol

Infections

• Spontaneous bacterial peritonitis
• Urinary tract infections
• Bronchopulmonary infection

Constipation

Protein rich foods

Gastrointestinal bleeding, mainly from dilated esophageal veins, is another common factor. Protein-rich foods (or blood in gastrointestinal bleeding) and the suppression of liver cell function caused by anemia and decreased hepatic blood flow contribute to the development of coma.

Patients with acute encephalopathy do not tolerate surgical operations well. Liver dysfunction worsens due to blood loss, anesthesia, and shock.

Acute alcoholic excess contributes to the development of coma due to the suppression of brain function and the addition of acute alcoholic hepatitis. Opiates, benzodiazepines and barbiturates suppress brain activity, the duration of their action is extended due to the slowing down of detoxification processes in the liver.

The development of hepatic encephalopathy can be facilitated by infectious diseases, especially in cases where they are complicated by bacteremia and spontaneous bacterial peritonitis.

Coma can occur due to eating high-protein foods or prolonged constipation.

Transjugular intrahepatic portosystemic shunting with stents (TIPS) promotes or worsens hepatic encephalopathy in 20-30% of patients. These data vary depending on the patient groups and selection principles. As for the effect of the shunts themselves, the probability of encephalopathy development is higher, the larger their diameter.

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