RU2462251C1 - Method of treating patients with chronic liver diseases in stage of latency and degree i manifested stage of hepatic encephalopathy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and aims at treating the patients with chronic liver diseases (CLD) in the stage of latency and degree I manifested stage of hepatic encephalopathy. The preparation Essentiale forte N is used. It is combined with prescribing the preparation Mucofalk. The course is 28-30 days.

EFFECT: method enables reducing dyspepsia events and encephalopathy manifestations.

5 ex, 3 tbl, 1 dwg

Description

The invention relates to medicine, namely to hepatology, and can be used in the treatment of patients with chronic liver diseases (CKD) with a latent stage and stage I clinically pronounced stage of hepatic encephalopathy.

In modern medical practice, to date, the problem of correction of hepatic encephalopathy in patients with CKD is one of the most relevant, as it is often caused by damage to people of the most working age. It is the damage to the nervous system that has a disadaptive effect on patients, determines the clinical picture, the severity of the course of the disease, and often leads to disability. In this regard, the restoration of the physical, mental and social status of patients with hepatic encephalopathy and the improvement of their quality of life takes on a national level [1, 2, 3, 4, 5].

“Hepatic encephalopathy” (PE) is a potentially reversible disorder of the central nervous system caused by metabolic disorders resulting from hepatic cell failure and / or portosystemic blood shunting [6].

According to the modern classification of portosystemic (hepatic) encephalopathy - Herber and Schomerus (2000) [7], two stages are distinguished: latent (subclinical) and clinically expressed. The significance of the secretion of latent hepatic encephalopathy (PE-L) is due to two reasons: 1. encephalopathy may precede the development of clinically severe liver failure; 2. psychomotor disturbances arising from PE-L have a negative impact on the quality of life of the patient, leading to reduced performance.

The stage of clinically pronounced PE, in turn, is divided into 4 degrees of development:

I - light (PE-1);

II - moderate;

III - severe;

IV - coma (lack of consciousness).

Considering that the pathogenesis of PE currently seems to be a multi-factorial multi-organ process that proceeds in parallel at 2 levels — the level of the liver and the level of the brain [8, 9], where the main role among neurotoxins is increased ammonia formation associated with a decrease in urea synthesis in the liver and glutamine, as well as with portosystemic blood shunting. Urease, a positive microflora of the gastrointestinal tract (decomposing urea and protein), serves as additional sources of increased ammonia formation [9, 10, 11, 12, 13]. Disorders of intestinal microflora are found in 90% of patients with CKD. The decreased detoxification function of microflora in intestinal dysbiosis increases the load on the enzymatic systems of the liver, which contributes to the occurrence of metabolic and structural changes in it [9].

In patients with PE, there is an intensive growth of the proteolytic flora, which, metabolizing protein residues (putrefactive flora), forms a large amount of gaseous ammonia, end products of protein metabolism, mercaptan, short-chain fatty acids, phenols, etc., entering the bloodstream and contributing to an increase in manifestation PE.

With an increase in the degree of PE, a change in the microbiocinosis of the colon is observed: there is a decrease in the number of lacto- and bifidobacteria, a steady increase in the number of urease-producing and proteolytic bacteria — clostridia, enterobacter, bacteroids, etc. It has been proven that putrefactive and pathogenic bacteria produce toxic products in the intestine, in particular E. Coli and clostridia - ammonia, amines, nitrosoamines, phenols, cresols, indoles, secondary acids, aglycines, bacteroids and streptococci - nitrosoamines, secondary bile acids, protei - ammonia, amines, indole [14].

Ammonia, in conditions of hyperammonium, in a non-ionized form (1-3% of the total amount of blood ammonia) easily penetrates the blood-brain barrier (BBB), disrupting the amino acid imbalance, leading to a decrease in the content of branched-chain amino acids (valine, leucine, isoleucine) and facilitating the transport of aromatic amino acids (tyrosine, phenylalanine, tryptophan) to the brain, as a result of which the synthesis of false neurotransmitters and serotonin is enhanced, leading to the development of a neurotoxic effect [6, 12, 15, 16]. Excessive intake of g-aminobutyric acid (GABA) in the brain also contributes to the development of PE, which also leads to an increase in the neuropsychiatric disorders characteristic of PE [16, 17].

Currently, given the multifactorial nature of the pathogenesis of PE, pathogenetic therapy includes three main groups of measures [9, 13]:

- Search for the causes of the development of PE, treatment of the underlying disease and elimination of the resolving factors of encephalopathy.

- A diet with a limited intake of animal protein with food, replacing it with vegetable; ensuring sufficient caloric intake to prevent a negative nitrogen balance, reduce the degree of hyperammonium.

- Drug therapy using several classes of drugs:

I) Drugs that reduce the concentration of blood ammonia:

1. - Reducing the flow of ammonia from the colon:

A) Nonabsorbable antibiotics (neomycin, rifaximin, paromomycin, ciprofloxacin) suppress the "ammonia" microflora in the colon, reduce the risk of developing spontaneous bacterial peritonitis and, possibly, other infections, as resolving factors of PE [18, 19, 20, 21].

B) Osmotic laxatives based on lactulose (duphalac), lactitol (export). The following mechanisms of action are considered: an increase in the growth of the number of lactobacilli, suppression of the growth of urea-positive bacteria, modification of bacterial metabolism (increased metabolism of carbohydrates and a decrease in protein decomposition), a decrease in the glutamine-dependent formation of ammonia in the ileum and in the pH of the colon, difficulty in absorbing ammonia, and facilitating the diffusion of ammonia from the blood vessels vessels of the mucous membrane into the lumen of the colon, action as osmotic laxative non-metabolizable products di aharidov [22, 23, 24, 25, 26], which in turn contributes to an increased excretion of nitrogenous products. The effectiveness of lactulose in PE was evaluated in many studies and ranged from 50% to 95% [27, 28, 29, 30].

2. - Binding blood ammonia (benzoate, phenylacetate) [31].

3. - Stimulating the neutralization of ammonia in the ornithine cycle in the liver and in the glutamine synthetase reaction in the liver and muscles (ornithine aspartate (hepamerz)) [6, 32, 33, 34, 35].

II) Drugs that reduce inhibitory processes in the central nervous system:

A) The antagonist of benzodiazepine receptors is flumanesil.

B) Branched chain amino acids - a positive effect of the application is associated with inhibition of the breakdown of its own protein in the liver and muscles, stimulation of protein synthesis, anabolic effect and protect astroglia from damage caused by the action of ammonia. The administration of branched chain amino acids to patients with protein intolerance can improve the nutritional status of patients without the development of new episodes of PE [36, 37, 38].

III) Preparations with a different mechanism of action:

A) Antioxidants that slow down or prevent oxidative stress (cytoflavin, dipan, etc.) [39, 40].

B) Zinc, which reduces the activity of lipid peroxidation and is itself a cofactor of many enzymes, including urea synthesis [41].

B) The preparation of a-lipoic acid, the molecule of which includes thiol groups (berlition) [41, 42].

In each case, the choice of treatment regimen depends on the clinical manifestations of the disease, the presence of subclinical, acute or chronic encephalopathy, the nature of the main pathological process.

Nevertheless, despite the experience of using various drugs for treating PE, currently in the literature there is only data on osmotic laxatives based on lactulose and lactylol for treating PE, and there is no data on the possibility of using other groups of laxatives for treating patients with PE.

As a prototype, we have chosen a method of treating hepatic encephalopathy, which consists in the use of the drug Dufalac, belonging to the group: Laxative drug with osmotic properties. Hypoammoniaemic agent [43].

DUFALAC ^® [43]

Group affiliation: Laxative drug with osmotic properties. Hypoammoniaemic agent.

Description for trade name: DUFALAC ^®

Dosage form:

Syrup transparent, viscous, colorless to light yellow with a brownish tint 100 ml lactulose 66.7 g

Excipients: purified water.

15 ml - disposable bags (10) - packs of cardboard.

200 ml - polyethylene bottles (1) complete with a measuring cup.

500 ml - polyethylene bottles (1) complete with a measuring cup.

1 l - polyethylene bottles (1) complete with a measuring cup.

Pharmachologic effect.

Laxative drug with osmotic properties. It has a hyperosmotic laxative effect, stimulates intestinal motility, improves the absorption of phosphates and calcium salts, and helps to remove ammonium ions.

Lactulose is split by the intestinal flora of the colon into low molecular weight organic acids, which leads to a decrease in pH and an increase in osmotic pressure and, as a consequence, an increase in the volume of intestinal contents, which, in turn, leads to an increase in intestinal motility and a change in the consistency of the stool. Constipation disappears and the physiological rhythm of the colon is restored.

With hepatic encephalopathy or hepatic precoma or coma, the effect of the drug is due to the suppression of proteolytic bacteria by increasing the number of acidophilic bacteria (for example, lactobacilli), the transition of ammonia into ionic form due to acidification of the contents of the colon, bowel movement due to lower pH in the colon and osmotic effect, and also reducing nitrogen-containing toxic substances by stimulating bacteria utilizing ammonia for bacterial protein synthesis.

Reduces the reproduction of salmonella.

Pharmacokinetics

Absorption is low. Practically not absorbed, it reaches the large intestine, where it is split by intestinal microflora. Fully metabolized when used in doses up to 45-70 ml. When used in higher doses, it is partially excreted unchanged.

Dosage regimen.

Doses of Dufalac in the treatment of constipation and with the aim of softening the stool for medical purposes are presented in the table.

The patients: Initial dose Maintenance dose Adults 15-45 ml 10-25 ml Children 7-14 years old 15 ml 10 ml Children 3-6 years old 5-10 ml 5-10 ml Children under 3 years old 5 ml 5 ml

As a rule, the dose can be reduced after 2 days of admission, depending on the needs of the patient.

The drug should be taken 1 time / day in the morning with meals. The clinical effect occurs in 1-2 days. The dose or frequency of administration is increased if, within 2 days of taking the drug, there is no improvement in the patient's condition. To soften the stool, the same doses are prescribed as with constipation.

In the treatment of hepatic coma and precoma, Dufalac ^{® is} prescribed 30-45 ml of syrup 3 times / day. Then they switch to an individually selected maintenance dose at which soft stools are observed at most 2-3 times / day, so that the pH of feces is in the range of 5.0-5.5.

In acute cases, Dufalac ^® can be prescribed in the form of enemas in the ratio of 300 ml of Dufalac ^® syrup and 700 ml of water.

Indications for use of the drug DUFALAC: ^®

- constipation: regulation of the physiological rhythm of the colon;

- softening the stool for medical purposes (for hemorrhoids, surgery on the colon and in the anus);

- hepatic encephalopathy: treatment and prevention of hepatic precoma and coma.

Side effect.

From the digestive system: in the first days, flatulence is possible (as a rule, passes independently after 2 days); possibly nausea, vomiting, abdominal pain; when using the drug in high doses, abdominal pain and diarrhea (dose adjustment is required).

From the side of metabolism: when used in high doses for a long time in the treatment of hepatic encephalopathy due to concomitant diarrhea, electrolyte imbalance is possible.

Other: electrolyte imbalance due to diarrhea.

Contraindications to the use of the drug DUFALAC: ^®

- galactosemia;

- intestinal obstruction;

- Hypersensitivity to the active substance or fructose, galactose, lactose.

Caution should be given to patients with diabetes.

The use of the drug DUFALAC ^® during pregnancy and lactation:

Lactulose can be used safely during pregnancy and during lactation (breastfeeding).

Special instructions:

In the absence of a therapeutic effect within 2 days or with the resumption of constipation after treatment, the patient should consult a doctor.

The dose commonly used for constipation should not be a problem for patients with diabetes. The dose used to treat hepatic precoma or coma is usually much higher and therefore should be clarified when given to patients with diabetes mellitus.

With prolonged use of the drug (more than 6 months) in elevated doses, the level of electrolytes in blood plasma should be regularly monitored.

When using the drug in patients with lactase deficiency, it should be borne in mind that 15 ml of syrup contains up to 1.5 g of galactose and up to 0.9 g of lactose.

Influence on the ability to drive vehicles and control mechanisms:

The use of Duphalac does not have or has a slight effect on the ability to drive a car or drive cars and mechanisms.

Overdose.

No cases of overdose have been reported. When using the drug in very high doses, abdominal pain and diarrhea are possible.

Treatment: dose reduction or discontinuation of the drug.

Drug interaction.

Due to the mechanism of action of lactulose, which is to lower the pH in the colon, drugs that are released depending on the pH of the colon (such as 5-aminosalicylic acid preparations) can be inactivated.

Vacation conditions from pharmacies.

The drug is approved for use as a means of OTC.

Terms and conditions of storage.

The drug should be stored in a dark place, out of reach of children at a temperature of 10 ° to 25 ° C. If stored in the original and undamaged packaging, the shelf life is 3 years.

The technical result of the invention is the expansion of the arsenal of drugs for the treatment of patients with chronic liver diseases with a latent stage and grade I clinically pronounced stage of hepatic encephalopathy with the drug Mukofalk.

The technical result is achieved by the fact that patients with chronic liver diseases with a latent stage and stage I clinically pronounced stage of hepatic encephalopathy on the background of drug exposure, including taking the hepatoprotector Essentiale Forte N, the patient is additionally administered the drug Mukofalk for 28-30 days.

Mukofalk: Firm manufacturer - Dr. Falk [43]

Composition and form of release

Orange granules for the preparation of a suspension for oral administration of a light brown color with inclusions from brown particles of the peel and adjacent cells of the shell of dried plantain seeds (Plantago ovata) - 3.25 g, with an aromatic orange smell.

Excipients: sucrose, dextrin, citric acid, sodium alginate, sodium citrate, sodium chloride, sodium saccharinate, orange flavor.

Clinical and pharmacological group.

Laxative phytopreparation

Pharmachologic effect.

Laxative phytopreparation. Hydrophilic fibers from the shell of the seeds of plantain retain fluid in the digestive tract, due to this, the volume increases and the texture of the stool softens. The drug regulates intestinal activity, facilitating the passage of intestinal contents [43]. The shell of oval plantain seeds (Plantago ovata), also known as psyllium (psyllium), consists mainly of carbohydrates (> 90%) and, in addition, contains a small amount of plant proteins (3-4%), mineral and other components (3 -four%). At 85%, psyllium consists of soluble dietary fiber, such as gum (gum), mucus, part of hemicellulose. The main active ingredient is the mucus-like hydrocolloid, which is arabinoxylan, which has an extremely high rate of swelling and water retention [3, 44].

Three main fractions of the shell of the seeds of Plantago ovata were selected, which are responsible for almost the entire carbohydrate composition and make up about 90% of the total psyllium mass:

- Fraction A (15-20%) - a fraction insoluble in alkaline medium and not fermented by bacteria, is a kind of ballast substance that normalizes intestinal motility.

- Fraction B - an active gel-forming, partially fermentable, has a laxative effect increasing the volume of the intestinal contents (due to water binding), provides softening of the stool, physiological lubrication of the intestinal wall and gliding of feces, provides a lipid-lowering effect, linking bile acids and increasing their excretion with feces, has a fixing effect in case of diarrhea, adsorbs exo- and endotoxins, transforms the liquid contents of the intestine into a more viscous mass and increases the transit time through the intestines ku.

Fraction C - a rapidly fermentable fraction slows down postprandial evacuation from the stomach and has pronounced prebiotic properties. As a result, there is a stimulation of the growth of bifidobacteria and lactobacilli and the formation of short chain fatty acids, which are the main source of energy for the epithelium of the colon [3, 8, 44, 45].

Pharmacokinetics [43].

Data on the pharmacokinetics of the drug Mukofalk not provided.

Indications for use of the drug MUKOFALK [43]

- constipation (including during pregnancy);

- anal fissures, hemorrhoids, the postoperative period during interventions in the anorectal region (in order to create a softer stool consistency);

- functional diarrhea, irritable bowel syndrome, colon diverticulosis, Crohn's disease (stool normalization).

Dosage regimen

Assign inside, adults and children over 12 years old - 1 sachet or 1 teaspoon 2-6 times / day.

Before use, 1 sachet or 1 teaspoon of granules is poured into a glass, which is slowly filled with cold water (150 ml), stirred and immediately drunk, then washed down with another glass of liquid.

Side effect [43]

Allergic reactions are possible.

In the first days of treatment, an increase in flatulence and the appearance of a feeling of fullness in the stomach are possible.

Contraindications to the use of the drug MUKOFALK

- organic strictures of the digestive tract;

- intestinal obstruction;

- decompensated diabetes mellitus;

- children's age up to 12 years;

- Hypersensitivity to the drug.

The use of the drug MUKOFALK during pregnancy and lactation.

Possible use during pregnancy according to indications.

Special instructions.

It should not be prescribed simultaneously with antidiarrheal drugs, as well as with drugs that inhibit intestinal motility. An interval of 30-60 minutes between taking Mukofalk and other drugs should be observed.

When taking the drug should drink at least 1.5 liters of fluid per day.

In patients with insulin-dependent diabetes mellitus, a decrease in the dose of insulin may be required.

Overdose

Data on an overdose of the drug Mukofalk not provided.

Drug interaction

Drug interaction of the drug Mukofalk not described.

Pharmacy Vacation Terms

The drug is approved for use as a means of OTC.

The method is as follows.

While taking the Essentiale Forte H hepatoprotector, Mukofalk is taken 1 sachet 3 times a day (1 sachet is poured into a glass that is slowly filled with cold water (150 ml), stirred and immediately drunk, then washed down with another glass of liquid (150 ml) within 28-30 days, according to indications, diuretics and / or beta-blockers and / or potassium preparations are prescribed.

A distinctive essential feature of the proposed method is that patients with chronic liver diseases with latent and I degrees of clinically pronounced stage of hepatic encephalopathy on the background of drug exposure, including the hepatoprotector Essentiale Forte N, the patient is additionally administered the drug Mukofalk for 28-30 days.

A causal relationship between the essential distinguishing feature and the result achieved.

For the first time, we have established the positive effect of the laxative phytopreparation Mukofalk on the resolution of the latent and first degree of the clinically pronounced stage of hepatic encephalopathy in patients with chronic liver diseases. In the Instructions section “Indications for the use of the MUKOFALK drug” [43], there is no information on the use of the drug to resolve the latent and first degree clinically pronounced stages of hepatic encephalopathy in patients with chronic liver diseases.

Mucofalk helps to normalize the microbiocenosis of the colon, increasing the level of representatives of the normal flora (bifidobacteria and lactobacilli) and reducing the number of representatives of opportunistic flora, thereby reducing the production of ammonia and the level of endotoxins, and normalizes stool, which helps to reduce the time of advancement of the colon contents to reduce the time for the formation of ammonia and accelerate its excretion. Perhaps, in this way, a hypo-ammonia effect is created that helps to resolve hepatic encephalopathy.

The duration of the drug Mukofalk provide maximum effectiveness in the treatment of patients with chronic liver diseases with latent and I degrees of clinically pronounced stage of hepatic encephalopathy.

Reception of a laxative phytopreparation Mukofalk may be an alternative to the use of osmotic laxatives for the treatment of latent and stage I clinically pronounced stages of hepatic encephalopathy in patients with chronic liver diseases.

A distinctive essential feature of the proposed method is new and expands the arsenal of laxative drugs for the treatment of patients with chronic liver diseases with latent and I degrees of the clinically pronounced stage of hepatic encephalopathy by taking the drug Mukofalk, which affects the microbiocinosis of the colon, forming a hypo-ammonia effect and contributing to the improvement of psychometric indicators.

We give examples of the clinical implementation of the method.

Example 1. (Mukofalk)

Patient B., 57 years old, A / card No. 19932. 12/19/2008

Complaints: general weakness, lethargy, tremor of the upper extremities, monotonous abdominal pain, a feeling of fullness in the abdomen, rumbling; flatulence, a change in the nature of the stool - a tendency to constipation. Objectively: at the time of inspection - in the mind, oriented, answers the questions correctly. Tremor of the upper extremities, the nature of the handwriting is changed.

On palpation: rumbling, increased tone in the sigmoid colon. Liver + 7 cm from the edge of the costal arch. Ascites is moderate.

From the anamnesis it is known that for 8 years, alcohol abuse is about 500 ml per day, since April 2007 yellowness of the skin, darkening of urine, and a decrease in appetite appeared. Treated on an outpatient basis - from honey. cards - HBsAg negative, antiHCV negative, abdominal ultrasound - hepatosplenomegaly; AsAT 165 u / l, AlAT 70 u / l, alkaline phosphate 168 u / l, GGTP 284 e / l. The condition is regarded as chronic toxic hepatitis, cirrhotic stage. In August 2007, nosebleeds were noted and was hospitalized at the Mariinsky Hospital. (Esophageal varicose veins (HRV) revealed) in a hospital - a course of hepatoprotectors and detoxification therapy. After discharge, he periodically took hepatoprotectors (Karsil, Hofitol, Zdorovka). He continued to abuse alcohol - 200 ml per day. In October 2008, on an outpatient examination: ECG: 65 heart rate sinus, incomplete blockade of the right bundle branch, hepatitis markers B and C (HBsAg, antiHCV) - negative, received diuretics on an outpatient basis (furosemide 40 mg every other day, carlsil). The condition is regarded as: chronic toxic hepatitis (ASH), cirrhotic stage, portal hypertension (hypersplenism, grade 1 esophagus esophagus). Over the past 2-3 weeks, tremor of the extremities, weakness, loss of appetite, and periodic drowsiness have been noted.

Conclusion Based on complaints, examination and clinical and laboratory data, patient B has chronic toxic hepatitis (ASH), cirrhotic stage of Child Pugh A.

Portal hypertension (hypersplenism, BPH of the esophagus of 1 degree).

Complication: hepatocellular insufficiency, class A, hepatic encephalopathy of the first degree of a clinically pronounced stage.

Clinical and laboratory tests during the treatment of patient B.

Hemoglobin level - 163 g / l, erythrocytes - 4.9 × 10 ¹² / l, white blood cells - 8.8 × 10 ⁹ / l, ESR - 22 mm / h, platelets - 85 × 10 ⁹ / l, AlAT - 62 units ./l, AsAT - 74 units / l, alkaline phosphatase - 254 units / l, GGTP - 148 e / l, total bilirubin - 34 units / l, total protein - 85 g / l, albumin - 35 g / l, Potassium - 3.4 mmol / l.

FGDS: BPH of the esophagus of 1 degree, chronic gastroduodenitis.

Ultrasound of the abdominal cavity: hepatosplenomegaly, v porte 15 mm, moderate ascites.

Hepatitis markers - B and C (HBsAg, antiHCV), RW - negative,

Number Connection Test (TSC) - 58 sec.

Test Line (TL) - 78 sec.

The number of errors when performing a TL (CO _TL ) is 9.

Neurologist consultation. Neurological history is not burdened.

In the neurological status - consciousness is clear, orientation of all kinds is preserved, speech is normal in pace, not conversational in conversation, answers questions correctly, sometimes slowly, reluctantly. Elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, mild anisocoria (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Light small amplitude tremor of the upper limbs. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. It presents hyperesthesia with a hyperpathic hue in the type of "socks" from the level of the ankles. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. There are no meningeal symptoms.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is encephalopathy of the 1st century, more likely hepatic origin.

The result of a microbiological examination for intestinal dysbiosis:

The level of lactobacilli - 10 ⁵ , bifidobacteria - 10 ⁶ , E. coli with normal enzymatic activity - 10 ⁶ , E. coli with reduced enzymatic activity - 0, other opportunistic microorganisms - 10 ² , Staphylococcus aureus - 10 ⁴ , yeast-like fungi of the genus Candida - 0.

Thus, the examined B., according to the results of bacteriological research, has changes characteristic of dysbacteriosis of the colon of the 2nd degree.

For 28 days, the patient received therapy with Essentiale Forte N, 2 capsules 3 times a day, Veroshpiron 50 mg in the morning on an empty stomach, Furosemide 40 mg in the morning on an empty stomach, Panangin 1 tablet 3 times, as well as Mukofalk 1 sachet, 3 times a day .

Clinical and laboratory analyzes of patient B. after treatment.

After treatment - weakness, lethargy, tremor of the upper limbs - does not bother, the handwriting is even. The chair is regular every day.

At the time of inspection - in the mind, focused, answers the questions correctly.

Hemoglobin level - 164 g / l, erythrocytes - 4.9 × 10 ¹² / l, white blood cells - 8.4 × 10 ⁹ / l, ESR - 15 mm / h, platelets - 96 × 10 ⁹ / l, AlAT - 38 units ./l, AsAT - 55 units / l, alkaline phosphatase - 224 units / l, GGTP - 116 e / l, total bilirubin - 24 units / l, total protein - 85 g / l, albumin - 35 g / l., potassium - 4.2 mmol / l.

TSCh - 38 sec.

TL - 59 sec.

CO _TL - 3.

Neurologist consultation. Neurological history is not burdened.

In neurological status - consciousness is clear, orientation of all kinds is preserved, speech is normal in pace, it is proactive in conversation, it answers questions correctly, sometimes slowly. Elements of emotional lability. The nature of the handwriting is not changed. Fields of vision are not changed, mild anisocoria (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

The result of a microbiological study of intestinal dysbiosis: Lactobacilli - 10 ⁷ , bifidobacteria - 10 ⁸ , E. coli with normal enzymatic activity - 10 ⁸ , E. coli with reduced enzymatic activity - 0, other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 10 ² , yeast-like fungi of the genus Candida - 0. Dysbacteriosis of 1 degree.

Given the clinical and biochemical picture, as well as psychometric testing, the patient has hepatic encephalopathy, a latent stage.

Example 2. (Mukofalk)

Patient S., 59 years old, card No. 4109. 03/19/2010

Complaints: general weakness, change in handwriting, drowsiness in the daytime, discomfort in the right hypochondrium, rumbling; flatulence, a change in the nature of the stool - a tendency to constipation.

Objectively: at the time of inspection - in the mind, oriented, answers the questions correctly.

On palpation: rumbling, increased tone in the sigmoid colon. Liver + 3 cm from the edge of the costal arch.

From the anamnesis, it is known that since 2000 he drew attention to a decrease in platelets in a clinical blood test, an increase in bilirubin to 40.0 e / l, and occasionally notes nosebleeds. Since August 2009, there was discomfort in the right hypochondrium. It was examined on an outpatient basis - HDF - esophageal esophageal hypertrophy - grade 2, no signs of bleeding. HBcor will put. By abdominal ultrasound - hepatosplenomegaly, HBV PCR denied, serodiagnosis - HBeAg neg, anti HBeAgIgG. CEA, AFP norm, diagnostics of copper and iron metabolism - N, ECG - heart rate 75, sinus rhythm, electrolyte changes. I did not receive antiviral therapy, I received hepatoprotective courses (Essler forte, 1 cap. 3 times 2 months.) Over the course of 2 weeks, weakness grew, notes a change in handwriting, drowsiness.

Conclusion Based on complaints, examination, and clinical and laboratory data, patient S. has the following:

Chronic viral hepatitis B, cirrhotic stage according to Child Pugh B.

Portal hypertension syndrome (BPH of the esophagus 2 degree, hypersplenism).

Complication: Hepatic cell deficiency, class B. Hepatic encephalopathy latent stage.

Clinical and laboratory tests during the treatment of patient C.: Hemoglobin level - 138 g / l, erythrocytes - 4.3 × 10 ¹² / l, white blood cells - 6.3 × 10 ⁹ / l, ESR - 17 mm / hour, platelets - 70 × 10 ⁹ / L, AlAT - 59 units / L, AsAT - 48 units / L, alkaline phosphatase - 134 units / L, GGTP - 33 e / L, total bilirubin - 30 units / L, total protein - 83 g / l, albumin - 41 g / l., Potassium - 4.5 mmol / l.

TSCh - 34 sec.

TL - 44 sec.

KO _TL - 6.

FGDS - esophageal esophageal hypertrophy of the esophagus - 2 degree, chronic astroduodenitis, without exacerbation, no signs of bleeding.

HBcor is positive, anti HCV is negative, RW is negative.

Ultrasound of the abdominal cavity - hepatosplenomegaly, ascites - not determined, v porte 14 mm.

Neurologist consultation. Neurological history is not burdened.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions correctly, slowly, with elements of emotional lability. The difficulty of writing, the nature of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

Conclusion At the time of the examination, there is no evidence for acute neurological pathology. There is latent encephalopathy, probably of hepatic origin.

The result of a microbiological examination for intestinal dysbiosis. The level of lactobacilli is 10 ⁷ , bifidobacteria - 10 ⁸ , E. coli with normal enzymatic activity - 10 ⁶ , E. coli with reduced enzymatic activity - 0, other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 10 ⁴ , yeast-like fungi of the genus Candida - 10 ² .

Thus, subject S., according to the results of a bacteriological study, has changes characteristic of dysbacteriosis of the colon of the 2nd degree.

For 28 days, the patient received therapy with Essentiale Forte N 2 capsules 3 times a day, Egilok 6.25 mg 2 times a day and Mukofalk 1 sachet 3 times a day.

Clinical and laboratory analyzes of patient C. after treatment.

After treatment - weakness, lethargy - does not bother, drowsiness - no, the handwriting is not changed.

At the time of inspection - in the mind, focused, answers the questions correctly. The chair is regular every day.

Hemoglobin level - 140 g / l, erythrocytes - 4.4 × 10 ¹² / l, white blood cells - 6.1 × 10 ⁹ / l, ESR - 12 mm / hour, platelets - 86 × 10 ⁹ / l, AlAT - 24 units ./l, AsAT - 28 units / l, alkaline phosphatase - 124 units / l, GGTP - 30 e / l, total bilirubin - 26 units / l, total protein - 84 g / l, albumin - 42 g / l., potassium - 4.3 mmol / l.

TSCh - 27 sec.

TL - 36 sec.

CO _TL - 0.

Neurologist consultation. In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions correctly, quickly. The character of the handwriting is even. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

The result of a microbiological examination for intestinal dysbiosis. The level of lactobacilli is 10 ⁸ , bifidobacteria - 10 ⁹ , E. coli with normal enzymatic activity - 10 ⁷ , E. coli with reduced enzymatic activity - 0, other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 0, yeast-like fungi of the genus Candida - 0. Dysbacteriosis of 0 degree.

Given the clinical and biochemical picture, as well as psychometric testing, the patient has no hepatic encephalopathy.

Example 3. (prototype method - Dufalac)

Patient K., 33 years old, card No. 19478. 12/18/2009

Complaints: change in handwriting, drowsiness, general weakness, pain in the right hypochondrium of a aching character, abdominal discomfort, heartburn, change in the nature of the stool - a tendency to constipation.

Objectively: at the time of inspection - in the mind, oriented, answers the questions correctly.

On palpation: rumbling, increased tone in the transverse colon and sigmoid colon. Liver +4 cm from the edge of the costal arch.

From the anamnesis it is known for 4 years - alcohol abuse - 300-200 ml in 3-5 days. Since July 2008, when he began to notice a decrease in appetite, icteric sclera. Continued to work. In October 2008, in a community clinic, during a biochemical blood test: AlAT - 76 e / l, AcAT - 139 e / l, total bilirubin 139 μmol / l, direct bilirubin - 139 μmol / l. He was hospitalized in a Botkin hospital, where it was revealed: an increase in GGTP to 352 U / L, IPT to 64%, virological markers of hepatitis C, A, B are negative. According to ultrasound, diffuse restructuring of the liver according to the type of cirrhotic. FGDS - HRV of the esophagus of the 2nd degree, portal hypertension. Received infusion therapy: electrolytes, vitamin C, riboxin, decinone. Discharged with improvement. Since 2008 - the use of alcohol - denied. Ambo-examination August 2009 - FGDS: Esophageal Esophageal Esophageal Examination 2 degrees, Ultrasound - diffuse restructuring of the liver according to the type of cirrhotic, Hepatosplenomegaly, v porte 14 mm. ECG - heart rate 70 sinus, electrolyte changes, Markers of hepatitis B, C, - negative. He took hepatoprotective courses (essentiale, heptral). Over the past 1 week notes a decrease in disability, daytime sleepiness, a change in handwriting (difficult to write).

Conclusion Based on complaints, examination, and clinical and laboratory data, patient K has the following:

Chronic toxic hepatitis (ASH), cirrhotic stage of Child Pugh A. Portal hypertension (BPH of the esophagus 2 degrees, hypersplenism).

Complication. Hepatic cell failure A, hepatic encephalopathy of the first degree of a clinically expressed stage.

Clinical and laboratory tests during the treatment of patient K. The hemoglobin level is 134 g / l, erythrocytes - 5.4 × 10 ¹² / l, white blood cells - 7.3 × 10 ⁹ / l, ESR - 22 mm / hour, platelets - 134 × 10 ⁹ / L, AlAT - 74 units / L, AsAT - 80 units / L, alkaline phosphatase - 213 units / L, GGTP - 413 e / L, total bilirubin - 27 units / L, total protein - 76 g / l, albumin - 49 g / l, potassium - 4.0 mmol / l.

TSCh - 53 sec.

TL - 72 seconds.

CO _TL - 7.

FGDS - esophageal esophageal hypertrophy of grade 2, no signs of bleeding, chronic gastritis, without exacerbation.

Ultrasound - diffuse reconstruction of the liver according to the type of cirrhotic, hepatosplenomegaly, v porte 14 mm.

Hepatitis markers - B and C (HBsAg, antiHCV), RW - negative,

Neurologist consultation. Neurological history is not burdened.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, it answers the questions correctly, slowly periodically in monosyllables, reluctantly, elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is encephalopathy of 1 tbsp., Probably of hepatic origin.

The result of a microbiological study of intestinal dysbiosis: The level of lactobacilli - 10 ⁵ , bifidobacteria - 10 ⁷ , E. coli with normal enzymatic activity - 10 ⁶ , E. coli with reduced enzymatic activity - 10 ³ , lactose-negative E. coli - 10 ² , and other conditionally pathogenic microorganisms - 10 ³ , Staphylococcus aureus - 0, yeast-like fungi of the genus Candida - 0.

Thus, the subject K., according to the results of bacteriological research, has changes characteristic of dysbacteriosis of the colon of the 2nd degree.

For 28 days, the patient received therapy with Essentiale Forte N, 2 capsules 3 times a day, Veroshpiron 50 mg in the morning on an empty stomach, and Dufalac at a dose of 30 ml 1 time / day in the morning with meals.

Clinical and laboratory tests of patient K. after treatment.

Within 28 days - weakness, lethargy - does not bother, drowsiness - no, an increase in working capacity is noted, the nature of the handwriting is not changed. The chair is regular every day.

At the time of inspection - in the mind, focused, answers the questions correctly.

Hemoglobin level - 142 g / l, erythrocytes - 5.5 × 10 ¹² / l, white blood cells - 7.2 × 10 ⁹ / l, ESR - 14 mm / h, platelets - 137 × 10 ⁹ / l, AlAT - 42 units ./l, AsAT - 51 u / l, alkaline phosphatase - 208 u / l, GGTP - 318 u / l, total bilirubin - 20 u / l, total protein - 76 g / l, albumin - 48 g / l, potassium - 4.2 mmol / l.

TSCh - 35 sec.

TL - 42 sec.

CO _TL - 4.

Neurologist consultation. Neurological history is not burdened.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, it answers questions correctly, periodically in monosyllables, elements with emotional lability. The nature of the handwriting is not changed, even. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected.

Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

The result of a microbiological examination for intestinal dysbiosis. The level of lactobacilli is 10 ⁷ , bifidobacteria - 10 ⁸ , E. coli with normal enzymatic activity - 10 ⁷ , E. coli with reduced enzymatic activity - 10 ² , lactose-negative E. coli - 0, other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 0, yeast-like fungi of the genus Candida - 0. Dysbacteriosis of 1 degree.

Given the clinical and biochemical picture, psychometric testing, the patient has hepatic encephalopathy, a latent stage.

Example 4. (hepatotropic drug Essential Forte N)

Patient M., 57 years old, card No. 16071. November 6, 2009

Complaints: general weakness, irritability, drowsiness in the daytime, poor sleep at night, abdominal discomfort that disappears after bowel movement; a feeling of fullness in the abdomen, increased gas formation, flatulence, a change in the nature of the stool - an alternation of diarrhea and constipation.

Objectively: at the time of inspection - in the mind, oriented, answers the questions correctly.

On palpation: rumbling, increased tone in the transverse colon and sigmoid colon. Liver +1 cm from the edge of the costal arch.

From the anamnesis it is known that since 2003, after psycho-emotional stress, I began to abuse alcohol - 100-200 ml in 4-5-6 days. In 2003 - yellowness of the skin was noted - was treated in the city infectious diseases hospital named after S.P.Botkin - with a diagnosis of chronic toxic hepatitis, with transformation into cirrhosis, portal hypertension. hypersplenism. BPV of the esophagus. Received therapy (hepatoprotectors, metabolic infusion therapy). After it was observed by the infectious disease specialist at the place of residence, he received hepatoprotectors (heptral, essentials, carlsil) courses. Since 2008 - alcohol denied. Outpatient examination August 2009 - Ultrasound of the abdominal cavity: diffuse changes in the liver, such as cirrhosis, hepatosplenomegaly, v porte 14 mm. ECG - sinus rhythm, the syndrome of early repolarization of the ventricles. Received Heptral IV training courses No. 10. Over the past 2 weeks, he has noted a frequent change of mood, irritability, drowsiness, and a frequent change of mood.

Conclusion Based on complaints, examination, and clinical and laboratory data from patient M., there is:

Chronic Toxic Hepatitis (ASH), cirrhotic stage of Child Pugh A.

Portal hypertension (BPV of the esophagus, hypersplenism).

Complication. Hepatic cell failure A hepatic encephalopathy latent stage.

Clinical and laboratory tests during the treatment of patient M.

Hemoglobin level - 134 g / l, erythrocytes - 4.4 × 10 ¹² / l, white blood cells - 4.4 × 10 ⁹ / l, ESR - 24 mm / hour, platelets - 89 × 10 ⁹ / l, AlAT - 60 units ./l, AsAT - 74 units / l, alkaline phosphatase - 309 units / l, GGTP - 269 e / l, total bilirubin - 42 units / l, total protein - 81 g / l, albumin - 33 g / l, potassium - 4.4 mmol / l.

TSCh - 36 sec.

TL - 61 sec.

CO _TL - 3.

FGDS: Esophageal Composition of the Esophagus, Chronic gastritis,

Ultrasound of the abdominal cavity: diffuse changes in the liver, such as cirrhosis, hepatosplenomegaly, v porte 14 mm.

Hepatitis markers - B and C (HBsAg, antiHCV), RW - negative,

Neurologist consultation: Neurological history is not burdened.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions correctly, slowly with elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is latent encephalopathy, probably of hepatic origin.

The result of a microbiological examination for intestinal dysbiosis. The level of lactobacilli is 10 ⁶ , bifidobacteria - 10 ⁷ , E. coli with normal enzymatic activity - 10 ⁷ , E. coli with reduced enzymatic activity - 10 ³ , lactose-negative E. coli - 10 ⁴ , other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 0 , yeast-like fungi of the genus Candida - 0.

Thus, examined M., according to the results of bacteriological research, has changes characteristic of dysbacteriosis of the colon of the 2nd degree.

For 28 days, the patient received therapy with Essentiale Forte N, 2 capsules 3 times a day.

Clinical and laboratory tests of patient M. after treatment.

After treatment - weakness decreased slightly, drowsiness in the daytime, as well as complaints of poor night sleep persisted, notes rapid irritability.

At the time of inspection - in the mind, focused, answers the questions correctly. A chair with a frequency of 1 time in 1-2 days. Periodically during the day, a feeling of fullness in the abdomen, increased gas formation, flatulence.

Hemoglobin level - 136 g / l, erythrocytes - 4.5 × 10 ¹² / l, white blood cells - 4.5 × 10 ⁹ / l, ESR - 23 mm / h, platelets - 89 × 10 ⁹ / l, AlAT - 35 units ./l, AsAT - 62 units / l, alkaline phosphatase - 269 units / l, GGTP - 248 e / l, total bilirubin - 40 units / l, total protein - 80 g / l, albumin - 33 g / l, potassium - 4.4 mmol / l.

TSCh - 36 sec.

TL - 60 sec.

CO _TL - 3.

Neurologist consultation.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions correctly, elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

The result of a microbiological examination for intestinal dysbiosis. The level of lactobacilli is 10 ⁶ , bifidobacteria - 10 ⁶ , E. coli with normal enzymatic activity - 10 ⁶ , E. coli with reduced enzymatic activity - 10 ³ , lactose-negative E. coli - 10 ³ , other conditionally pathogenic microorganisms - 0, Staphylococcus aureus - 0 , yeast-like fungi of the genus Candida - 10 ⁴ . Dysbacteriosis of the 2nd degree.

Given the clinical and biochemical picture, psychometric testing, the patient has hepatic encephalopathy, a latent stage.

Example 5. (comparison drug - Guttalax)

Patient L., 34 years old, card No. 3590. 03/13/2009

Complaints: general weakness, drowsiness, abdominal discomfort, which pass after bowel movement; increased gas formation, flatulence, a change in the nature of the stool - a tendency to constipation.

Objectively: at the time of inspection - in the mind, oriented, answers the questions correctly.

On palpation: rumbling, increased tone in the transverse colon and sigmoid colon. Liver +1 cm from the edge of the costal arch.

From the anamnesis it is known, for 2 years, periodically noted pain in the right hypochondrium of an aching nature. In January 2009, an increase in transominases, took hepatoprotectors (hofitol, karsil with effect) 03.03.09 revealed a positive anti HCV (ep. Number 21.000), ultrasound of the abdominal cavity showed hepatomegaly, diffuse liver changes v porte 10 mm. FGDS - VRV is not revealed. The ECG rhythm is sinus, without abnormalities. Over the past 1 week notes a change in handwriting, drowsiness, decreased ability to work.

Conclusion: Based on complaints, examination, and clinical and laboratory data from patient L, the following occurs:

Chronic viral hepatitis (HCV), minimal activity.

Complication: hepatic encephalopathy latent stage.

Clinical and laboratory tests during the treatment of a patient L.:

Hemoglobin level - 165 g / l, erythrocytes - 5.3 × 10 ¹² / l, white blood cells - 5.6 × 10 ⁹ / l, ESR - 23 mm / h, platelets - 206 × 10 ⁹ / l, AlAT - 119 units ./l, AsAT - 43 u / l, alkaline phosphatase - 129 u / l, GGTP - 69 u / l, total bilirubin - 55 u / l, total protein - 82 g / l, albumin - 44 g / l, potassium - 4.1 mmol / l.

TSCh - 35 sec.

TL - 52 sec.

CO _TL - 5.

Ultrasound of the abdominal cavity - hepatomegaly, diffuse changes in the liver v porte 10 mm.

FGDS - VRV is not revealed, gastroduodenitis without exacerbation.

Neurologist consultation: Neurological history is not burdened.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions slowly, correctly, sometimes monosyllabic, with elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

Conclusion: at the time of examination, there is no data for acute neurological pathology. There is latent encephalopathy, probably of hepatic origin.

The result of a microbiological study of intestinal dysbiosis: The level of lactobacilli - 10 ⁶ , bifidobacteria - 10 ⁶ , E. coli with normal enzymatic activity - 10 ⁷ , E. coli with reduced enzymatic activity - 10 ³ , lactose-negative E. coli - 10 ² , and other conditionally pathogenic microorganisms - 10 ⁴ , Staphylococcus aureus - 0, yeast-like fungi of the genus Candida - 10 ³ .

Thus, according to the results of bacteriological research, examined L. has changes characteristic of colonic dysbiosis of the 2nd degree.

For 28 days, the patient received therapy with Essentiale Forte N 2 capsules 3 times a day and Guttalax at a dose of 15 drops 1 time / day.

Clinical and laboratory tests of patient L. after treatment.

After treatment, the weakness decreased. Daytime sleepiness persists.

At the time of inspection - in the mind, focused, answers the questions correctly. The chair is regular 1 time every day.

Hemoglobin level - 167 g / l, erythrocytes - 5.3 × 10 ¹² / l, white blood cells - 5.4 × 10 ⁹ / l, ESR - 23 mm / h, platelets - 208 × 10 ⁹ / l, AlAT - 97 units ./l, AsAT - 34 u / l, alkaline phosphatase - 120 u / l, GGTP - 65 u / l, total bilirubin - 43 u / l, total protein - 82 g / l, albumin - 44 g / l, potassium - 4.2 mmol / l.

TSCh - 35 sec.

TL - 50 sec.

CO _TL - 5.

Neurologist consultation.

In neurological status - consciousness is clear, oriented in time and space, speech is normal in pace, answers questions slowly, correctly, sometimes in monosyllables, reluctantly, with elements of emotional lability. The character of the handwriting is changed - uneven. Fields of vision are not changed, (pupils S = D), photoreactions - live, eyeball movements in full, nystagmus - no, facial muscles are symmetrical, no bulbar disorders, no sensitive disorders on the face. Trigeminal exit points are painless. Violations of smell, hearing - not detected. Symptoms of oral automatism - no. Force paresis in the limbs, pathological stop signs - not detected. Tremor of the upper extremities is absent. Deep reflexes D = S, moderate liveliness, superficial abdominal reflexes preserved, D = S. Disorders of superficial sensitivity on the trunk and limbs does not show. Vibration sensitivity on the toes and hands is not reduced. Coordination tests are satisfactory. In the Romberg position - steady. Meningeal symptoms - no.

The result of a microbiological study of intestinal dysbiosis: Lactobacilli level - 10 ⁶ , bifidobacteria - 10 ⁷ , E. coli with normal enzymatic activity - 10 ⁷ , E. coli with reduced enzymatic activity - 10 ³ , lactose-negative E. coli - 10 ² , and other conditionally pathogenic microorganisms - 10 ⁴ , Staphylococcus aureus - 0, yeast-like fungi of the genus Candida - 10 ³ . Dysbacteriosis of the 2nd degree.

Given the clinical and biochemical picture, psychometric testing, the patient has hepatic encephalopathy, a latent stage.

The laxative drug Guttalax, manufacturer: BERINGER INGELHEIM PHARMA GmbH, widely used in gastroenterology, for the treatment of constipation, was taken as a comparison drug; and hepatoprotector Essentiale, manufacturer: Sanofi-Aventis

GUTTALAX ^® Guttalax - sodium picosulfate [43]

Manufacturer: BERINGER INGELHEIM FARMA GmbH

Release form, composition and packaging:

- Drops for oral administration in the form of a transparent, slightly colorless to yellowish viscous solution or slightly tan. ml (15 drops) sodium picosulfate (in the form of a monohydrate) 7.5 mg

Excipients: sodium benzoate, sodium citrate dihydrate, liquid sorbitol (non-crystallizing), citric acid monohydrate, purified water.

15 ml - plastic dropper bottle (1) - packs of cardboard.

30 ml - plastic dropper bottle (1) - packs of cardboard.

pharmachologic effect

Laxative drug. The active substance - sodium picosulfate - is a laxative of the triarylmethane group. As a local laxative, sodium picosulfate after bacterial cleavage in the colon has a stimulating effect on the mucous membrane of the colon, increasing peristalsis, and contributes to the accumulation of water and electrolytes in the colon. This leads to stimulation of the bowel movement, a decrease in evacuation time and softening of the stool.

Pharmacokinetics

After ingestion of sodium, picosulfate enters the colon. The absorption of the drug is negligible, which excludes its enterohepatic circulation. In the colon, sodium picosulfate is cleaved to form the active metabolite, bis- (p-hydroxyphenyl) pyridyl-2-methane. The time of development of the laxative effect of the drug is determined by the release rate of the active metabolite and is 6-12 hours. A small part of the drug enters the systemic circulation. There is no correlation between the laxative effect of the active metabolite and its concentration in the blood serum.

Indications for use of the drug GUTTALAX ^®

As a laxative in the following cases:

- constipation due to atony and hypotension of the colon (including in old age, in bedridden patients, after operations, after childbirth and during lactation);

- constipation caused by medication;

- to regulate the stool with hemorrhoids, proctitis, anal fissures (to soften the consistency of feces);

- gallbladder disease, irritable bowel syndrome with a predominance of constipation;

- constipation due to intestinal dysbiosis, dietary disorders.

Dosage regimen

The drug is prescribed orally.

Adults and children over 10 years of age are prescribed 10-20 drops (5-10 mg); children 4-10 years old - 5-10 drops (2.5-5 mg).

To obtain a laxative effect in the morning, the drug should be taken the night before.

Side effect

From the digestive system: discomfort; nausea, vomiting, cramping and pain in the abdomen, diarrhea.

Hypersensitivity reactions from the immune system are possible, including angioedema and skin reactions.

Contraindications to the use of the drug GUTTALAX ^®

- intestinal obstruction;

- obstructive bowel disease;

- acute inflammatory bowel disease;

- severe abdominal pain, accompanying nausea and vomiting, which may be a symptom of the above serious conditions;

severe dehydration;

- children's age up to 4 years;

- Hypersensitivity to sodium picosulfate and other components of the drug.

Patients with a rare hereditary fructose intolerance disease should not take the drug.

The use of the drug GUTTALAX ^® during pregnancy and lactation

There are no data on reliable and well-controlled studies in pregnant women. Long-term experience of use did not reveal a negative effect of the drug on pregnancy. Taking the drug in the first trimester of pregnancy is contraindicated. In the II and III trimesters of pregnancy (as with other laxatives), the drug is possible only as directed by a doctor.

The active metabolite and its glucuronides are not excreted in breast milk. Thus, the drug can be used during breastfeeding.

special instructions

It is not recommended to take the drug daily without consulting a doctor for more than 10 days. Long-term use of the drug in high doses can lead to dehydration, electrolyte imbalance, hypokalemia.

1 ml of drops contains 450 mg of sorbitol. The maximum recommended daily dose for the treatment of adults and children 4-10 years old contains 600 mg and 300 mg of sorbitol, respectively. The drug does not have taste, so it can be added to food when used in children. Children should take the drug only as directed by a doctor.

Influence on the ability to drive vehicles and control mechanisms

Not marked.

Overdose

Symptoms: when taking high doses, diarrhea, dehydration, decreased blood pressure, impaired water-electrolyte balance, hypokalemia, and convulsions are possible. In addition, there are reports of cases of colon muscle ischemia associated with taking doses of Guttalax significantly exceeding those recommended for the usual treatment of constipation.

Guttalax ^® , like other laxatives, with chronic overdose can lead to chronic diarrhea, pain in the abdomen, hypokalemia, secondary hyperaldosteronism, urolithiasis. Due to chronic abuse of laxatives, damage to the renal tubules, metabolic alkalosis, and muscle weakness associated with hypokalemia can develop.

Treatment: to reduce the absorption of the drug after ingestion, you can induce vomiting or gastric lavage. It may be necessary to replenish the fluid and correct the balance of electrolytes, as well as the appointment of antispasmodics.

Drug interaction

With the simultaneous use of Guttalax in high doses and diuretics or corticosteroids, the risk of developing electrolyte disorders (hypokalemia) increases.

The simultaneous administration of antibiotics can reduce the laxative effect of Guttalax.

An electrolyte imbalance can increase sensitivity to cardiac glycosides.

Pharmacy Vacation Terms

The drug is approved for use as a means of OTC.

Terms and conditions of storage

The drug should be stored out of the reach of children, protected from light at a temperature of no higher than 30 ° C; do not freeze. Shelf life is 3 years.

ESSENTIALE ^® FORTE N (ESSENTIALE ^® FORTE N) Manufacturer: Sanofi-Aventis [43]

Release form, composition and packaging.

- Hard gelatin capsules, brown colors, opaque, oblong; content capsules - oily pasty mass tan color. 1 caps. soybean phospholipids containing 76% (3-sn-phosphatidyl) choline (synonyms - "essential" phospholipids, EPL ^® ) 300 mg

Excipients: solid fat, soybean oil, hydrogenated castor oil, ethanol 96%, ethyl vanillin, 4-methoxyacetophenone, α-tocopherol.

Capsule composition: gelatin, purified water, titanium dioxide (E171), yellow iron oxide dye (E172), black iron oxide dye (E172), red iron oxide dye (E172), sodium lauryl sulfate.

10 pieces. - blisters (3) - packs of cardboard.

10 pieces. - blisters (10) - packs of cardboard.

Clinical and pharmacological group. Hepatoprotector

Pharmacological properties: hepatotropic drug. The active substance of the drug is the so-called essential phospholipids (EPL ^® -substance), which are a highly purified fraction of phosphatidylcholine. The determining component of this fraction is dilinoleoylphosphatidylcholine. EPL ^® in their chemical structure are similar to endogenous membrane phospholipids, surpassing them in their functional properties due to the high content of polyunsaturated fatty acids, especially linoleic acid. Phospholipids are the main structural elements of cell membranes and organelles. They take part in the differentiation, reproduction and regeneration of cells. The functional significance of phospholipids is based on their amphiphilic properties, which allow to regulate the permeability of the cell membrane. They improve the function of membranes, in particular, ion exchange, the process of intracellular respiration, biological oxidation, affect the binding of enzymes of intracellular respiration in mitochondria, as well as the process of oxidative phosphorylation in energy metabolism of cells. Under physiological conditions, the synthesis of phospholipids satisfies the normal needs of hepatocytes, which contain a sufficient amount of phospholipids.

It is known that the structure of cell membranes and the function of enzyme systems in liver diseases are violated. The biosynthesis of phospholipids is violated, the deficiency of which leads to a violation of the function of the cell membrane. These processes are especially pronounced in mitochondria, which are approximately 30% phospholipids and in which the most important metabolic processes, including oxidative phosphorylation, are carried out. With a deficiency of phospholipids, a violation of fat metabolism occurs, which leads to fatty degeneration of the liver. Due to their pharmacological properties, essential phospholipids eliminate these disorders, promote the regeneration of cell membranes, reactivate broken membrane-bound enzyme systems and receptors, increase the detoxification ability of the liver and thus normalize its function.

When taking Essential Forte N inside, more than 90% of the drug is absorbed in the small intestine. The main amount under the influence of phospholipase-A breaks down to 1-acyl-lyso-phosphatidylcholine, 50% of which is immediately ethylated to polyunsaturated phosphatidylcholine even during absorption in the small intestine. Polyunsaturated phosphatidylcholine enters the bloodstream through the lymphatic vessels primarily in combination with HDL and is transported to the liver. The maximum level of phosphatidylcholine in the blood is reached 6-24 hours after taking the drug and is on average 20%.

The elimination half-life for the choline component is 66 hours, for saturated fatty acids - 32 hours. About 5% of the drug is excreted in the feces.

Indications:

- chronic hepatitis;

- cirrhosis of the liver;

- fatty degeneration of the liver of various etiologies;

- toxic liver damage;

- pregnancy toxicosis;

- psoriasis (as adjuvant therapy);

- radiation syndrome

Dosage regimen:

Essentiale ^® Fort N is prescribed orally by 2 capsules 2-3 times / day. while eating. The course of treatment is at least 3 months and, if necessary, can be continued or repeated.

Capsules should be swallowed whole with a little water.

Side effect.

Essentiale ^® Fort N is generally well tolerated.

From the digestive system: rarely - a feeling of discomfort in the abdomen, loose stools.

Other: allergic reactions possible.

Contraindications to the use of the drug ESSENTIAL ^® FORTE N

- individual intolerance to the drug.

The use of the drug ESSENTIAL ^® FORTE N during pregnancy and lactation

Perhaps the use of the drug during pregnancy according to indications.

Use for impaired liver function.

Possible use according to indications.

Overdose

No cases of drug overdose have been reported at this time.

Drug interaction

Drug interaction of the drug is not described.

Pharmacy Vacation Terms

The drug is approved for use as a means of OTC.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 21 ° C. Shelf life is 3 years.

As can be seen from the above examples, the results of treatment by the present method (examples No. 1 and No. 2) are not inferior to the results of treatment by the method of the prototype (example No. 3), as evidenced by clinical, laboratory and psychometric data. Example No. 4 (monotherapy of Essentiale Forte N) demonstrates the absence of a positive effect on psychometric indicators, which proves the presence of this effect in the inventive method by the administration of the drug Mukofalk (examples No. 1 and No. 2), rather than the hepatotropic drug Essentiale Forte N. Example No. 5 is given for evidence of the absence of a psychometric effect when taking laxatives of the triarylmethane group.

The inventive method has been tested in 85 patients with CKD, PE-L or grade I clinically expressed stage of hepatic encephalopathy. All patients were divided into 4 groups:

Group 1 - 30 people with CKD with PE-L or PE-1. The treatment program included hepatoprotector from the group of essential phospholipids (Essential Forte N), 2 caps. 3 times a day and Mukofalk 1 sachet 3 times a day (1 sachet is poured into a glass, which is slowly filled with cold water (150 ml), stirred and immediately drunk, then washed down with another glass of liquid (150 ml) for 28- 30 days.

Group 2 - (comparison 1) - comprised 20 people with CKD with PE-L or PE-1. The treatment program included hepatoprotector from the group of essential phospholipids (Essential Forte N), 2 caps. 3 times a day and Dufalac at a dose of 30 ml 1 time / day in the morning with meals for 28-30 days.

Group 3 - (comparison 2) - comprised 20 people with CKD with PE-L or PE-1. The treatment program included hepatoprotector from the group of essential phospholipids (Essential Forte N), 2 caps. 3 times a day for 28-30 days.

4 group - (comparison 3) - 15 people with CKD with PE-L or PE-1. The treatment program included hepatoprotector from the group of essential phospholipids (Essential Forte N), 2 caps. 3 times a day and Guttalax in a dose of 15 drops 1 time / day for 28-30 days.

Patients with edematous syndrome were additionally prescribed Veroshpiron 50 mg in the morning on an empty stomach.

The distribution of CKD patients with latent stage or degree I of the clinically pronounced stage of hepatic encephalopathy and detection with colon dysbiosis are presented in table 1.

All 85 patients with CKD who have intestinal dysbiosis showed general complaints of: stool disorders characterized by alternating diarrhea and constipation; feeling of fullness in the abdomen due to increased gas formation, rumbling; abdominal pain, often monotonous, pulling and bursting, sometimes strong, colicky, a feeling of fullness in the stomach; aerophagia, belching, nausea with a saved appetite; flatulence, difficulty in defecation; abdominal pain as intestinal colic, which occurs after bowel movement.

The survey included:

1) a double bacteriological examination of feces for dysbiosis before the start of therapy and a month after treatment according to standard schemes;

2) monitoring the manifestation of hepatic encephalopathy [9, 46]:

- psychometric testing (numbers connection test, line test);

- assessment of cognitive functions was carried out using the "10 words" method of A.R. Luria (impaired memory) and Schulte tables (impaired attention);

- Diagnosis of depressive states according to the Zunge technique;

- consultation of a neurologist and psychiatrist to exclude other causes of encephalopathy. Neurological symptoms were evaluated: tremor of fingers, paresthesia of limbs, increase in tendon reflexes, change in handwriting;

- biochemical and clinical blood analysis.

The dynamics of clinical manifestations in patients with CKD with latent and I degrees of clinically expressed stage of hepatic encephalopathy during therapy

According to the results of the observation, it was found that during treatment in groups 1 and 2 the asthenic and dyspeptic syndrome decreased on average 6 to 7 days after the start of treatment and was observed in 21 (70.0%) patients - in the 1st group, 16 (80%) people - in the 2nd group. Whereas in group 3, by day 6-7, there was a decrease in dyspeptic syndrome in only 4 (20.0%) patients, and in group 4 - in 6 (40%) patients. An increase in working capacity after 30 days against the background of the treatment was noted by 56.6% of patients in the 1st group and 65% of patients in the 2nd group. In group 3, only 3 people (15.0%) noted an increase in working capacity, and in group 4 - 4 people (27%). Normalization of cognitive functions and fine motor skills was noted after 30 days - in group 1 - in 67% of patients, in group 2 - in 70% of patients, in groups 3 and 4 improvement in cognitive functions and fine motor skills occurred only in 10.0% and 13.0% of patients.

Thus, after 28-30 days, against the background of the therapy, in patients of the 1st and 2nd groups, an improvement in clinical symptoms is comparable.

Changes in laboratory data in patients with CKD with latent and I degrees of clinically pronounced stage of hepatic encephalopathy during treatment (see Tables 2, 3 and 4).

The positive dynamics in the state of clinical and laboratory research of group 1 corresponded to the results of group 2, presented in tables 2, 3 and 4.

Dynamics of latent and grade I clinically pronounced stages of hepatic encephalopathy in patients with chronic liver diseases before and after therapy (see Histogram 1).

An analysis of the results of the psychometric tests after the therapy has confirmed the improvement or restoration of psychomotor functions in 70% of patients of the 2nd group, 63% of patients of the 1st group, 10% of people (2 people) from group 3, and 13% (2 people .) - group 4. The results of psychometric testing (TSC and TL) of patients with CKD are presented in histogram 1. In the 1st and 2nd groups, KO _TL before treatment was 6.2 ± 1.1, and 6.3 ± 1, 1, respectively, after therapy, the CO of _TL was 1.1 ± 0.5, (p <0.05) and 1.2 ± 0.5, (p <0.05), respectively, in the 3rd and 4th the group of KO _TL before treatment was 6.0 ± 1.2, and 6.2 ± 1.3 s Responsibly, after the therapy, the CO of _TL was 5.7 ± 1.1, (p> 0.05), and 6.0 ± 1.2, (p> 0.05), respectively.

In our study, a significant inverse correlation was also observed between the time of TSC and TL and the level of growth of lactobacilli in patients with CKD and PE-L and grade I stage I - r = -0.29 and -0.20, p <0.05 , and a direct relationship to the growth of clostridia r = 0.20 and r = 0.19, p <0.05, Staphylococcus aureus r = 0.24 and r = 0.23, p <0.05, fungi of the genus Candida r = 0.41 and r = 0.36, p <0.05, and the time to complete the TSC and the growth of hemolytic microorganisms r = 0.24, p <0.05.

The above data indicate the effective use of the laxative phytopreparation Mukofalk for the treatment of patients with chronic liver diseases with a latent stage and stage I clinically pronounced stage of hepatic encephalopathy. The data obtained are comparable with the prototype method (the use of the osmotic laxative drug Dufalac in the treatment of patients with latent and I degrees of clinically pronounced stage of hepatic encephalopathy).

Thus, the claimed method expands the arsenal of drugs for the treatment of patients with chronic liver diseases with a latent stage and stage I clinically pronounced stage of hepatic encephalopathy due to the introduction of the drug Mukofalk.

Table 1 Distribution of patients with chronic liver diseases with latent and I degrees of the clinically expressed stage of hepatic encephalopathy and the detection of colonic dysbiosis Groups: Colon dysbiosis n (%) 1 degree 2 degree 3 degree 1 group, n = 30 13 (40%) 11 (32%) 6 (32%) 2 group, n = 20 7 (22%) 9 (26%) 4 (21%) 3 group, n = 20 7 (22%) 8 (24%) 5 (26%) 4 group, n = 15 5 (16%) 6 (18%) 4 (21%) Total: 85 32 (100%) 34 (100%) 19 (100%)

Claims (1)

A method of treating patients with chronic liver diseases with a latent stage and the first degree of a clinically pronounced stage of hepatic encephalopathy, consisting in a drug effect, including the Essentiale Forte H hepatoprotector, characterized in that the patient is additionally injected with Mukofalk for 28-30 days.

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