What Is Hepatic Encephalopathy?

Hepatic encephalopathy (HE), also known as hepatic coma, refers to a syndrome of central nervous system dysfunction based on metabolic disorders caused by severe liver disease. Its main clinical manifestations are disturbance of consciousness, behavioral disorders and coma. There are acute and chronic encephalopathy.

Basic Information

nickname

Hepatic coma

English name

hepatic encephalopathy

Visiting department

Neurology, Gastroenterology

Multiple groups

People with severe liver disease

Common causes

Liver cirrhosis, severe viral hepatitis, post-portal shunt, etc.

Common symptoms

Disorders of consciousness, behavioral disorders, and coma based on liver disease

Causes of hepatic encephalopathy

The primary causes of hepatic encephalopathy include severe viral hepatitis, severe toxic hepatitis, drug-induced liver disease, acute fatty liver during pregnancy, various types of liver cirrhosis, postoperative portal-systemic shunt, primary liver cancer, and other diffuse In the terminal stage of liver disease, hepatic encephalopathy is most common in patients with cirrhosis, accounting for about 70%. There are many factors that induce hepatic encephalopathy, such as upper gastrointestinal bleeding, high protein diet, large amount of potassium diuresis, ascites, use of sleeping, sedation, anesthesia, constipation, uremia, infection or surgical trauma. These factors are generally through: increase neurotoxicity or increase the toxicity of neurotoxicity. Improve the sensitivity of brain tissue to various toxic substances. Increase the permeability of blood-cerebrospinal fluid barrier and induce encephalopathy.

Clinical manifestations of hepatic encephalopathy

It varies according to the type of liver disease, the degree of liver cell damage, the onset of onset, and the causes. Because the underlying diseases that cause hepatic encephalopathy are different, their clinical manifestations are also complicated and changeable. The variability of early symptoms is a characteristic of this disease. But it also has its common characteristics: it is reflected as neuropsychiatric symptoms and signs. It has the manifestations of primary liver diseases and its unique clinical manifestations, which are generally characterized by changes in personality, behavior, intelligence, and disturbance of consciousness.

Onset

Can be urgent and slow. Acute hepatic encephalopathy has a rapid onset, and the prodromal period is extremely short. It can quickly enter a coma. Most of the coma occurs after jaundice, and there are people who are misdiagnosed as mental illness before the jaundice appears. The onset of chronic hepatic encephalopathy is concealed or gradually developed, which is often not easy to find at first, and is easy to be misdiagnosed and missed.

2. Personality change

It is often the earliest symptom of this disease, mainly that those with an original extroverted personality show depression, while those with the original introverted personality show euphoria.

3. Behaviour change

At first, it may be limited to some informal behaviors, such as scribbling, spraying water, spitting, throwing confetti and cigarette butts, searching, drowning, and dragging tables and chairs in the room. Wait for meaningless actions.

4. Changes in sleep habits

Often manifested as sleep inversion, it is also known as imminent coma. This phenomenon has been found to be related to the disorder of the patient's serum melatonin secretion, which indicates that the central nervous system's excitation and inhibition are in a disordered state, which often indicates that hepatic encephalopathy is imminent. advent.

5. The appearance of liver odor

Due to liver failure, the body contains sulfur amino acid metabolism intermediates (such as methyl mercaptan, ethyl mercaptan and dimethyl sulfide, etc.) exhaled through the lungs or a characteristic odor emitted through the skin. This smell has been described by scholars as rotten apple, garlic, and fishy.

6. Flutter-like tremor

It is the most characteristic neurological sign of hepatic encephalopathy and has early diagnostic significance. Unfortunately, flutter-like tremor is not present in all patients. The method is: instruct the patient to stretch out his forearm, spread five fingers, or the wrist is overstretched and fixed, the patient's palm-finger and wrist joints can appear rapid flexion and extension movements, which often occur 1 to 2 times per second There are also 5 to 9 times per second, and often accompanied by side movements of the fingers. At this time, the patient may be accompanied by subtle tremor and ataxia of the entire upper limb, tongue, chin, and jaw. Either on one side or on both sides. This tremor is not characteristic and can also be seen in patients with heart failure, kidney failure, lung failure and other patients. Tremors often disappear after a patient's sleep and coma, and can still occur after waking.

7. Visual impairment

rare. However, in recent years, domestic and foreign literature reports have gradually increased. Patients with hepatic encephalopathy may have visual impairment and blindness as their main clinical manifestations. This kind of visual impairment is transient and functional. It can also resume with the recovery of hepatic encephalopathy. The pathogenesis is unknown, and most are thought to be as complicated as hepatic encephalopathy, which is the result of a combination of factors.

8. Intellectual Disability

With the progress of the disease, the patient's intelligence changes, manifested as unclear concepts of time and space, blurred concepts of characters, unclear words, upside down, difficulty writing, decreased computing and counting ability, wrong digital connection, and early identification of liver disease. Simple and reliable method for encephalopathy.

9. Disorder of Consciousness

After the mental retardation, a more obvious disturbance of consciousness appeared, from drowsiness and lethargy to coma, and all reactions and reflections disappeared. There are also comatoses who gradually move from mania. The main clinical manifestations of hepatic-encephalic degenerative hepatic encephalopathy are: mental retardation, dysphonia, memory loss, mental retardation, ataxia, tremor rigidity, spastic paraplegia (hepatic myelopathy), etc. But there was no obvious disturbance of consciousness.

Liver encephalopathy examination

Blood ammonia

Most patients with chronic hepatic encephalopathy and pse have elevated blood ammonia. However, patients with acute hepatic encephalopathy may have normal blood ammonia.

2. EEG

The electrical activity emitted by brain cells when active, the EEG of a normal person is an alpha wave, 8 to 13 times per second. Electroencephalograms in patients with hepatic encephalopathy show slower rhythms. Stage - patients show delta waves or three-phase waves, 4 to 7 times per second; when in a coma, they show high delta waves, less than 4 times per second. The changes in EEG are not very specific. Similar changes can be seen in uremia, respiratory failure, and hypoglycemia. In addition, EEG has less diagnostic value for subclinical hepatic encephalopathy and stage i hepatic encephalopathy.

3. Evoked potential

It is the potential generated by the cerebral cortex or subcortex after receiving information from various sensory organs, which is different from the spontaneous electrical activity of the brain recorded by EEG. Evoked potentials can be divided into visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP) according to the different parts of the stimulated sensation. Evoked potential tests are mostly used for the diagnosis and research of mild hepatic encephalopathy. . There is still a p300 event-related potential that is not affected by the physiological characteristics of the stimulation site compared to traditional evoked potentials. Patients with mild hepatic encephalopathy have a prolonged incubation period for p300.

4. Psychological Intelligence Test

It is suitable for the diagnosis of hepatic encephalopathy and the screening of mild hepatic encephalopathy. Its disadvantage is affected by age and education. Older people and people with lower education levels are slower in testing and affect results. Other methods that can be used to detect mild hepatic encephalopathy include scribing and series of dot tests.

5. Imaging examination

Brain edema can be found in patients with acute hepatic encephalopathy by CT or MRI of the head. Patients with chronic hepatic encephalopathy can find different degrees of brain atrophy. In addition, MRI examinations revealed an increase in T1-weighted signals in the basal ganglia, which was related to the deposition of manganese there. The developed magnetic resonance spectroscopy (MRS) is a method to determine the content of metabolites in some parts of a living body on a high magnetic field (more than 1.5t) magnetic resonance scanner. The proton (h1) mrs was used to detect the gray matter and apical cortex of the brain of patients with chronic liver disease. It was found that the content of certain organic osmotic substances such as choline, glutamine, and creatine changed. Hepatic encephalopathy, mild hepatic encephalopathy, and even general liver cirrhosis patients have some changes.

6. Critical visual flicker frequency detection

Mild stellate cell swelling is an early pathological change, while stellate cell swelling (alztrimer type II) will change the glial-neuronal signal transmission. The morphological changes of retinal glial cells are similar to aiztrimier type astrocytic cells, so Retinal glial cell disease can be used as a marker of glial astrocytic lesions in the brain. It can be quantitatively diagnosed by measuring the critical visual flash frequency. Preliminary application results suggest that the method is sensitive, simple and reliable, and can be used to find and detect mild hepatic encephalopathy.

Diagnosis of hepatic encephalopathy

1. Early diagnostic test (intelligence test)

For patients with atypical early clinical manifestations of hepatic encephalopathy, in addition to careful examination and close observation of the condition, the following methods need to be performed to help early diagnosis.

(1) Digital connection test Randomly print 25 Arabic numerals on paper, and instruct the patient to connect with a pen in a natural size and a line, record the connection time, and check the frequency of connection errors. The method is simple and can detect early patients, whose abnormalities may even change before the EEG, and can be used as an indicator of efficacy judgment.

(2) The signature test allows patients to sign their own names every day. If the handwriting is not correct, early encephalopathy can be found.

(3) Building blocks such as using a match to build a five-pointed star, or draw a simple diagram, or do simple addition or subtraction.

Clinical diagnosis

Comprehensive analysis combined with laboratory inspection. Based primarily on the patient:

(1) Have a history of severe liver disease and / or extensive portal-systemic shunt (after portal hypertension or portal-systemic shunt), clinical manifestations, and abnormal liver function tests.

(2) A series of neurological and psychiatric symptoms appear.

(3) Often accompanied by an increase in blood ammonia and / or a decrease or inversion of the branched chain amino acid / aromatic amino acid ratio.

(4) Abnormalities of EEG or visual evoked potential and rule out other reasons.

(5) The diagnosis can be made if the cerebrospinal fluid pressure and routine examination are normal.

(6) It is more conducive to diagnosis if the cause of hepatic encephalopathy can be found.

3. Diagnosis of cerebral edema

Cerebral edema is usually judged by signs of elevated intracranial pressure. However, the characteristics of intracranial hypertension are often not obvious when the patient is in stage hepatic encephalopathy (deep coma), and it is easy to attribute all the manifestations in this period to hepatic encephalopathy and ignore the existence of cerebral edema, so that many patients missed during their lifetime Diagnosis of cerebral edema. If patients with hepatic encephalopathy have a deeper coma, increased blood pressure, slow pulses, flooding, deep breathing, and obvious edema of the ball-bound membrane, treatment with dehydrating agents such as mannitol can quickly work, and the diagnosis of cerebral edema can be established. In addition, head CT and magnetic resonance imaging can help diagnose brain edema. Monitoring intracranial pressure with an intracranial pressure monitor is an important technique currently applied.

Hepatic encephalopathy treatment

General treatment

Removing the cause of hepatic encephalopathy is the basic principle of its general treatment and the basis of other drug treatments, including the following measures.

(1) Adjusting the diet structure Patients with liver cirrhosis often have a negative nitrogen balance, so they should be supplemented with sufficient protein. However, a high-protein diet can induce hepatic encephalopathy, so patients with hepatic encephalopathy should limit protein intake and ensure thermal energy supply. Stage III-IV patients should not be supplemented with protein from the gastrointestinal tract. Nasal feeding or intravenous injection of 25% glucose solution should be prohibited. Stage - patients should limit the protein to 20g / day. If the condition improves, 10g protein can be added every 3 to 5 days to gradually increase the patient's tolerance to protein. After the patient has fully recovered, he can consume 0.8 to 1.0 protein per kilogram of body weight per day to maintain basic nitrogen balance. Because plant proteins (such as soy products) are rich in branched chain amino acids and non-absorbent fibers, the latter can promote intestinal peristalsis, and after being broken down by bacteria can also lower the pH of the colon, which can accelerate the excretion of poisons and reduce ammonia absorption. Therefore, patients with hepatic encephalopathy should prefer plant protein. Dairy products are rich in nutrition and can be taken in moderation if the condition is stable.

(2) Use of sedatives such as barbiturates and benzodiazepines with caution can activate GABA / BZ complex receptors. In addition, patients with liver cirrhosis have prolonged drug half-life due to liver function decline. Therefore, the use of these drugs may induce or worsen Hepatic encephalopathy. If you have a mania, you should disable these drugs and try antihistamines such as promethazine and chlorpheniramine (parmin).

(3) Correct electrolyte and acid-base balance disorders. Patients with liver cirrhosis may suffer from low potassium alkalosis due to low food intake, excessive diuresis, and excessive discharge to the abdomen, which may induce or aggravate hepatic encephalopathy. Therefore, the dosage of diuretics should not be too large. When a large amount of ascites is discharged, a sufficient amount of albumin should be input intravenously to maintain effective blood volume and prevent electrolyte disturbances. Patients with hepatic encephalopathy should often detect serum electrolytes and blood gas analysis. If there is hypokalemia or alkalosis, it should be corrected in time.

(4) Hemostasis and clearing of intestinal hemorrhage . Upper gastrointestinal bleeding is an important cause of hepatic encephalopathy. Therefore, those with esophageal varices bleeding should take various emergency measures to stop bleeding and input blood products to supplement blood volume. The following measures can be taken to clear the intestinal hemorrhage: oral or nasal feeding of lactulose, lactitol solution or 25% magnesium sulfate, enema with normal saline or weak acid solution (such as acetic acid), and dilute lactulose to 33.3% for enema.

(5) Other patients should be given oxygen if they are hypoxic, and those with hypoglycemia can be injected with hypertonic glucose intravenously, and if infection should be controlled in time.

2. Drug treatment

Because ammonia poisoning is the main cause of hepatic encephalopathy, reducing the absorption of ammonia and strengthening the excretion of ammonia are the main means of drug treatment.

(1) Reduce the production and absorption of intestinal ammonia Lactulose (-galactose) is a synthetic disaccharide, which will not be broken down in the small intestine after oral administration, and can be digested by lactobacillus and feces after reaching the colon. Bacteria such as cocci break down into lactic acid and acetic acid to lower the pH of the intestine. After intestinal acidification, it is not good for the growth of urease-producing bacteria, but it is beneficial to the growth of urease-producing lactic acid bacteria, which reduces the ammonia produced by the intestinal bacteria. In addition, the acidic intestinal environment can reduce the absorption of ammonia, and Promote the infiltration of ammonia from the blood into the intestines. The effect of lactulose is definite, and it can be used for the treatment of hepatic encephalopathy and mild hepatic encephalopathy in various stages. Adverse reactions mainly include abdominal distension, abdominal pain, nausea, and vomiting. In addition, its sweet taste makes it unacceptable for a few patients. lactitol (-galactose sorbitol) is another synthetic disaccharide, which is broken down by the bacteria of the colon into acetic acid and propionic acid to acidify the intestinal tract. Lactitol has a similar effect to lactulose, but it has low sweetness, good taste and fewer adverse reactions. For those who lack lactase, lactose can also be tried. Due to the lack of lactase in the small intestine of some people, lactose is not broken down and absorbed in the small intestine after oral administration of lactose. After entering the colon, it is decomposed by bacteria to acidify the intestine and generate gas to make the intestines move Increase and promote bowel movements. Oral antibiotics can inhibit intestinal urease-producing bacteria and reduce ammonia production. Commonly used antibiotics are neomycin, metronidazole, rifaximin and the like. Oral neomycin is rarely absorbed. However, long-term use may cause ototoxicity and renal toxicity, and should not exceed 1 month. The efficacy of metronidazole is similar to that of neomycin, but its gastrointestinal side effects are relatively large. Rifaximin is not absorbed orally. Rifaximin is not absorbed orally. The effect is the same as that of neomycin. Oral administration of certain beneficial bacteria that do not produce urease can inhibit the growth of harmful bacteria and reduce ammonia production. The efficacy of Lactobacillus acidophilus is still controversial, but the efficacy of Enterococcus faecalis SF68 used in recent years is relatively accurate. The method of taking SF68 is to stop using it for 2 weeks after taking it for 4 weeks. It can be used repeatedly. Oral beneficial bacteria have no toxic side effects.

(2) Promote the metabolism of ammonia in the body L-Ornithine-L-aspartic acid is a mixed preparation of ornithine and aspartic acid, which can promote the urea cycle (ornithine cycle) in the body and reduce blood ammonia. Intravenous injection of 20 g of OA daily can reduce blood ammonia and improve symptoms. The adverse reactions are nausea and vomiting. Ornithine--ketoglutarate has the same ammonia reduction mechanism as OA, but its efficacy is not as good as OA. Sodium benzoate can be combined with nitrogen-derived substances to form excretion of uric acid from the kidney to reduce blood ammonia. The main adverse reactions are indigestion. Sodium phenylacetate can be combined with glutamine to form phenylacetylglutamine and excreted by the kidneys. The two are basically not used clinically at present. Glutamate and ammonia combine to form glutamine to reduce blood ammonia. There are two types of potassium glutamate and sodium glutamate. The ratio of the two can be adjusted according to blood potassium and blood sodium. Glutamate is alkaline. Vitamin C can be injected before use. It is not suitable for those with alkalemia. Arginine can promote the urea cycle and reduce blood ammonia. The drug is acidic and suitable for alkalosis patients.

(3) Flumazenil, a GABA / BZ (gamma aminobutyric acid / benzodiazepine) complex receptor antagonist, can antagonize neurosuppression caused by endogenous benzodiazepines. For patients with hepatic encephalopathy stage III to IV, it has a wake-up effect. Intravenous flumazenil works quickly, often within a few minutes, but is maintained for a short time, usually intravenously within 4 hours; or continuous intravenous drip. Although the efficacy of flumazenil in the treatment of hepatic encephalopathy is still controversial, the PSE level and NCT score can be significantly changed after selective use.

(4) The preparation for reducing or antagonizing the branched-chain amino acid (BCAA) of pseudo-neurotransmitter is a compound amino acid mainly composed of BCAA such as leucine, isoleucine, valine acid. The mechanism is a competitive BCAA-based complex amino acid. Its mechanism is to competitively inhibit the entry of aromatic amino acids into the brain and reduce the formation of pseudo-neurotransmitters. Its efficacy is still controversial, but for malnourished people who cannot tolerate proteins, BCAA supplementation can help improve their nitrogen balance.

(5) Other drugs Manganese deposition in the basal ganglia of patients with hepatic encephalopathy, and the effectiveness of manganese repellents needs further study. L-carnitine can strengthen energy metabolism. The important mechanism of the ammonia poisoning hypothesis is that ammonia interferes with energy metabolism. The efficacy of L-carnitine remains to be confirmed.

3. Other treatments

(1) Reduce portal shunt For portal shunt refractory hepatic encephalopathy, interventional methods can be used to reduce the shunt by using a steel ring or plugging the portal vein system. Reduction of portal shunt For portal shunt refractory hepatic encephalopathy, interventional methods can be used to reduce the shunt by using steel rings or balloon embolization of the portal vein system.

(2) Molecular sorbent recirculation system (MARS) for artificial liver, hemoperfusion, hemodialysis and other methods can remove blood ammonia and other toxic substances, and have certain effects on acute and chronic hepatic encephalopathy.

(3) Hepatocellular liver transplantation is an effective means of treating various end-stage liver diseases, and is an indication of severe and refractory hepatic encephalopathy.

(4) Hepatocyte transplantation is the transplantation of human hepatocytes through the portal vein or intrahepatic, and it can also be performed in the spleen. The transplanted hepatocytes can survive and have synthetic functions, but they also require a large number of hepatocytes. In clinical.

4. Symptomatic treatment

(1) Correct water and electrolyte disorders and acid-base balance imbalance, and the total daily liquid intake should not exceed 250Oml. The amount of fluid in patients with liver cirrhosis and ascites should be controlled (usually about urinary volume plus 1000ml) to prevent blood dilution and hyponatremia and aggravate coma. Potassium deficiency is supplemented with potassium chloride, and those with alkalosis can be intravenously infused with arginine solution.

(2) Protect brain cell function. Use an ice cap to reduce intracranial temperature to reduce energy consumption and protect cell function.

(3) For deep coma to protect the unobstructed airway, tracheotomy should be performed to expel sputum to give oxygen.

(4) Prevent cerebral edema by intravenously injecting dehydrating drugs such as hypertonic glucose and mannitol to prevent cerebral edema.

Prognosis of hepatic encephalopathy

The prognosis of the disease depends on the cause. Those with clear incentives and easy to eliminate (such as bleeding, potassium deficiency, etc.) have a better prognosis. The prognosis of hepatic encephalopathy caused by acute liver failure (severe viral hepatitis or drug-induced hepatitis) is more severe than that of patients with cirrhosis and portal shunts. Those with ascites, jaundice, and bleeding tend to suggest poor liver function and poor prognosis. Hepatic encephalopathy caused by fulminant liver failure has the worst prognosis.

Actively prevent and treat liver diseases. Patients with liver disease should avoid all factors that induce hepatic encephalopathy. Closely observe the patients with liver disease, timely discover the prodromal and coma manifestations of hepatic encephalopathy, and perform appropriate treatment.