Bile acids and itchy skin. Pruritus associated with cholestasis

Skin itching in liver disease is one of the main diagnostic criteria. Often it is accompanied by yellowing of the skin, which indicates a malfunction of the gland, gallbladder, congestion. The skin begins to itch long before it becomes a yellowish color.

Itching with liver ailments causes a strong feeling of discomfort, a desire to comb the skin. It appears throughout the body or in certain areas of the cover. It does not act as a separate pathology, but is a sign of an internal failure or external influence.

In diseases of the liver, itching is a common occurrence. Therefore, we will consider why you want to itch, how to distinguish itching of the liver from other disorders in the body, what is the treatment.

The etiology of itching in liver pathologies

Hepatic itching appears due to the influence of bile acids. They are formed from cholesterol in the liver cells, after which they are transported along with the flow of bile to gallbladder, 12 duodenal ulcer. Normally, they do not enter the bloodstream, do not accumulate in the body, since they have a toxic effect.

Itchy sensations in a person may develop due to liver disease or other internal organs, because of allergic reaction- both isolated - to some external allergen, and due to liver intoxication.

The skin begins to itch and burn with liver problems. Medical experts identify the following reasons:

Itching of the skin can have a harmless nature - malnutrition - the consumption of a large amount of spices, fatty, fried, smoked foods.

cholestasis

The occurrence of the disease is based on cholelithiasis and oncological pathologies, against which the full outflow of bile is disturbed. Cholestatic itching develops due to the penetration of bile acids into the circulatory system.

Distinguish chronic and acute form of cholestasis, intrahepatic and extrahepatic form. Additional symptoms include sleep disturbance, digestive disorders, fever, general weakness, headaches.

Itching of the skin with hepatitis C

Itching may indicate hepatitis C. According to doctors, the discomfort of HCV occurs due to the accumulation of toxic components that cannot be effectively removed from the body naturally. When the liver fails, bilirubin and bile acids enter the bloodstream.

An increased concentration of these components leads to yellowing of the skin, sclera of the eyes, mucous membranes, itching, rash.

Cholestatic hepatosis of pregnancy

Intrahepatic jaundice of unknown origin. In a pregnant woman, the functionality of the liver is impaired due to an increase in the susceptibility of cells to sex hormones. It is difficult to diagnose such an ailment, since an enlarged uterus interferes with palpation, and many diagnostic methods are contraindicated during this period.

Alcoholic hepatosis

is a common illness. When alcohol enters the body, it is transformed into components that destroy liver cells. Connective tissue grows in them. If there is no timely treatment, the likelihood of developing cirrhosis is high.

Symptoms - the liver “itches”, pain in the right hypochondrium (may go to the bottom), occurs at different times of the day, most often the character is aching. Patients complain of weakness increased gas formation, nausea, loss of appetite, emotional instability.

Biliary cirrhosis

With this pathology, itching of the skin affects the upper and lower extremities. Often it is the only symptom of pathology, it can last from several months to a couple of years.

Clinic of hepatic pruritus

Skin itching in diseases of the liver and pancreas almost always manifests itself in conjunction with other symptoms on the skin. It is important to recognize the disease initial stage which provides a favorable prognosis.

Patients are mistaken in believing that if there is no pain, then the disease is not serious. Not present in the liver nerve endings and when it appears pain syndrome, this indicates a running stage.

Localization of itching - any, occurs at any time of the day - morning, evening, lunch. Has a tendency to intensify. Additional symptoms include increased sweating, swelling of the legs, face, peeling of the skin, microcracks on the skin, stripes of blue color on the surface of the cover, and various rashes.

Skin manifestations in liver diseases

Rashes against the background of gland pathologies are similar to allergic manifestations, although there are features. In case of violation of the liver, the patient may experience the following types of rashes:

• Pustules. They appear due to a disorder in the production of immunoglobulins by the gland.
• Allergy-like spots are a reaction to a deterioration in the functionality of an organ, a decrease in detoxification function.
• Small bruises.
• Vascular stars. Localization - arms, legs, neck, face, stomach.
• Against the background of hepatitis, yellow plaques are formed that affect the arms and legs, eyelids, and armpits.

Palmar erythema - feature hepatic diseases. It appears as spots of a red hue, which disappear when pressed, then reappear.

How to distinguish itchy liver from other disorders

It is almost impossible to determine the cause of the itching on your own, but you can try. Itching that occurs with liver ailments must be distinguished from allergic manifestations. In the latter case, there is a certain localization, the whole body rarely itchs. Antihistamine medications help to alleviate the condition.

Ways and methods of treatment

To establish a diagnosis, you should consult a doctor. Based on the diagnostic results obtained, treatment is prescribed. It is complex and includes medicines and special meals. Medications are selected in accordance with the disease, which is the primary source of the problem.

In some cases, surgery is required. If the cause of cholestasis is a failure in the outflow of bile, which arose due to the blockage of the channels, which led to intoxication, then drainage is installed. Drainage helps to remove excess dangerous components, which quickly eliminates negative symptoms.

Medication use

In drug therapy, opioid acid antagonists, bile acid derivatives, and high-dose ursodeoxycholic acid preparations are used.

To get rid of itchy sensations, you need to take medicine:

1. Sorbents - help to remove toxic components from the intestines (Enterosgel).
2. Vitamins - ascorbic acid, tocopherol, retinol, vitamin K.
3. Anti-inflammatory drugs to reduce the intensity of the inflammatory process.
4. Immunostimulants - used against the background of a reduced immune status.
5. Probiotics normalize the work of the digestive tract.
6. Hepatoprotectors - help restore gland cells, improve the functionality of the organ, accelerate regeneration processes.

For bacterial infection, antibiotic therapy, and antiviral drugs are used against the background of a viral one.

Additionally, it is recommended to stop drinking alcohol and smoking. It is necessary to wear clothes made from natural materials to reduce the irritating effect on the skin. Cooling gels and ointments help to temporarily alleviate the condition.

Diet

Table number 5 is recommended if the patient's history chronic form hepatitis, cirrhosis, dysfunction of the biliary tract, cholelithiasis. Main principle diet food- reduce fat intake. Table salt in the diet is limited or completely abandoned. Cooking methods - boiling, baking, stewing.

The basis of the patient's diet should consist of fruits and vegetables. They contain a lot of pectins and plant fiber. It is important to observe the drinking regime - drink at least 1500 ml of fluid per day. Diet is not an alternative to drug therapy, but only an integral part of it.

During the diet, you can eat low-fat varieties of fish, meat, vegetables, fruits, pasta, bran and whole grain bread. You can not eat mushrooms, legumes, sweets - sweets, ice cream, chocolate, fatty meat, canned food, offal. Banned carbonated and caffeinated drinks, energy drinks, alcoholic products. Garlic, onions, sorrel and radishes, cauliflower are not allowed from vegetables.

To get rid of itchy skin, you need to establish the true cause. Only its elimination helps to level the symptom. At timely treatment you can count on a favorable prognosis and the absence of complications from the liver.

Itchy sensations on the skin do not always act as manifestations of allergies or dermatological problems. People suffering from hepatic disorders may also experience unpleasant reactions from the epidermis. Itching of the skin of the body with liver diseases is common. Such a violation occurs in the presence of internal pathologies and leads to severe discomfort. Consider why this happens and what to do in this case.

Why does the skin itch with liver pathology

Hepatic itching is associated with impaired circulation. Pathology develops when the lumen is blocked and goes through several stages:

• Under normal conditions, the substances produced by it leave the body as part of bile without any negative consequences.
• As a result of a failure, acids can enter the bloodstream, and from there to all organs, including the skin.
• Irritated nerve endings lead to the appearance of uncomfortable sensations.

Among the primary causes of skin itching, liver damage, cholestatic, and cancerous processes can be distinguished. The presence of a rash on the body is also associated with the intake of certain medications that damage the liver.

In addition to liver diseases, the skin can itch due to. For this reason, the normal passage of bile is disrupted, it is absorbed into the blood, which leads to discomfort on the skin.

Differences between ordinary itching and hepatic

In many people, the skin with liver diseases is subject to extensive irritation. Sometimes it itches without a clear localization.

Skin irritation in hepatic problems is often excruciating, prone to prolonged leakage. Other features that make it possible to distinguish manifestations of hepatic itching from ordinary scratching are:

• sensations are very intense;
• increased discomfort at night;
• scratching does not lead to relief;
• rashes on the face, limbs, torso.

Skin manifestations of liver diseases take a variety of forms. They can take the form of spots, bruises, stars. Liver problems are often accompanied (yellowing of the skin and mucous membranes), painful sensations under the ribs on the right, dyspeptic disorders.

An important feature of hepatic itching is the low effectiveness of antihistamines, which alleviate the patient's condition with other forms of skin irritation.

Additional symptoms and changes in tests

Itching with cirrhosis of the liver is a sign of the initial stage of the disease. With cirrhosis, irritation is more often manifested on the surface of the upper or lower extremities. has a paroxysmal or permanent character, often extends to the epigastric region of the abdomen.

It is possible to identify the cause thanks to the general and. When making a diagnosis, the specialist evaluates the changed cholesterol, blood serum protein. Additionally, a person with pruritus is prescribed a coagulogram, which helps to identify disorders in the liver and other organs of the gastrointestinal tract.

How to get rid of liver itching

To remove skin rashes in liver disease, you need a comprehensive treatment that will eliminate the root cause. Important points in the fight against unpleasant symptoms are compliance prescribed by a specialist, taking medications. Pin Results conservative therapy possible through the use of funds.

With itching provoked by liver diseases, it is recommended to follow the following rules:

• Exclude overheating of the body and skin in particular.
• During the period of illness, do not visit baths or saunas.
• In the warm season, bathe under a cool shower.
• Refuse to wear things made from artificial materials.
• Treat itchy areas with a coolant.
• Avoid smoking, alcohol.

It is important to avoid frequent stressful situations that can aggravate the condition, to exclude immoderate physical exercise. If the skin itches during drug therapy, treatment with them should be immediately abandoned.

It is possible to eliminate a rash in liver diseases due to the implementation of dietary principles:

• exclusion from the menu of products that harm the liver (fatty, spicy, smoked);
• compliance with the 5-time diet;
• eating small meals, avoiding overeating.

For people with liver diseases and skin itching, a special diet has been developed -. The menu corresponding to it contains mainly baked, stewed dishes (fried ones are completely excluded), cereal soups cooked in vegetable broths, seafood, eggs, butter, sweet berries, fruits. Xylitol can be added to meals instead of sugar for itching. From sweets, the use of natural honey, marmalade, homemade jam is recommended.

For liver disorders that cause itching on the surface of the skin, it is useful to drink water without gas, vegetable juices, rosehip infusion, weak tea.

Medications

Skin itching in liver disease requires the use of effective pharmacological products:

• active agents that restore the structure of the liver tissues (Heptral, Karsil, Choludexan, Galstena);
• sorbents needed to remove toxins from the body, toxic substances (Enterosgel, Atoxil, activated carbon);
• medicines, (Hofitol, Tsikvalon, Exhol);
• lipid-lowering drugs that normalize cholesterol levels (Cholestyramine).

Additionally, with itching of the liver, anti-inflammatory and immunostimulating drugs, probiotics, fat-soluble vitamins (A, D, E, K) are indicated. If infections are detected, antibacterial or antiviral agents are prescribed.

The speedy recovery and prevention of possible relapses of hepatic itching is facilitated by taking drugs with an increased concentration of vitamins C, group B.

Folk remedies

If you are concerned about skin rashes with liver disease, it is recommended to use. You can improve the condition of the organ and eliminate itching with the help of such recipes:

1. Infusion medicinal herbs. Mix 6 tbsp. l. chopped herb wormwood and plantain with 1 liter of boiling water. The tool is ready for use after insisting overnight. For skin itching, drink the infusion on an empty stomach in the morning and before bedtime.
2. Infusion. To make such a natural medicine that renews liver cells, crushed grains are poured with boiling water and kept in a thermos for 12 hours. The finished medicine is drunk before meals for ½ cup. In pharmacies, you can buy a finished product - Ovesol tea.
3. Rosehip decoction. Boil fresh or dried berries in water for 10 minutes, then stand for at least 12 hours. Add sorbitol to the resulting composition. For liver diseases, take a decoction daily, shortly before breakfast, in a volume of 1 cup.

Itching of the skin, provoked by disturbances in the functioning of the liver, is completely eliminated in case of early contact with a specialist, and adequate treatment. After completing the therapeutic course, it is important to follow all the recommendations of the doctor.

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Is itching during cirrhosis of the liver the main symptom and what is its treatment?

In cirrhosis, healthy human liver cells are replaced by scar tissue. This disease is incurable and dangerous for the body with the complications that accompany it. Very often, the reason for going to the doctor and, as a result, the detection of cirrhosis, is severe itching of the skin of the body. It may also be accompanied by a rash or spots.

The liver is one of the most important organs that takes on a number of vital functions. It neutralizes toxins that pollute our body. Therefore, no need to overload the liver alcoholic drinks and fatty foods, because nothing goes unnoticed for the liver.

In most cases, this disease affects middle-aged and elderly men. It is impossible to diagnose the disease yourself. But if a person has symptoms such as a sharp weight loss, nausea, a feeling of bitterness in the mouth, pain in the right hypochondrium, then you should immediately contact a specialist who will give a referral for an examination and prescribe a competent treatment.

Causes of the disease

Causes of cirrhosis of the liver are:

• alcohol abuse;
• Viral hepatitis B and C;
• Drug poisoning;
• Blockage of the hepatic veins;
• Autoimmune hepatitis (in the human body, substances are produced that destroy the organ);
• genetic predisposition.

Diagnostics

Even a highly qualified specialist cannot independently, based only on the patient's stories, make such a complex diagnosis.

To correctly diagnose the disease will help him:

1. Ultrasound of the liver (the size of the lobes of the organ, its structure and shape, the condition of the ducts that excrete bile are assessed and compared with normal averages);
2. Computed tomography (more expensive than ultrasound diagnostics, in which the region of the right hypochondrium is irradiated with x-rays and then a two-dimensional image of the organ is displayed on the computer);
3. Determination of the level of proteins and bilirubin in the blood;
4. Blood clotting test (blood clots slowly in liver disease).

Cholestasis as a symptom of cirrhosis

Cholestasis is a process, an abnormal condition of the liver and bile outflow system, in which the quality and quantity of secreted bile changes. It stagnates in the blood and, as a result, penetrates the body, poisoning it. The main symptom is severe itching of the skin. Arising on the palms and feet, it subsequently spreads throughout the body.

This is a very unpleasant feeling that does not allow a person to sleep and work normally. In some severe cases, it leads to depression and suicidal thoughts.

The main substances that are found in bile and cause itching are:

1. acids;
2. Copper;
3. Bilirubin (the result of the breakdown of red blood cells);
4. Other metals.

An important factor that indicates pathology in the body is the fact that during cirrhosis of the liver, itching cannot be soothed by antihistamines. It is also necessary to know that the disappearance of itching does not indicate an improvement in the patient's condition. This indicates liver failure.

It is important for the patient to remember that no matter how painful the itching of the skin may be for him, you should not comb your wounds, because the infection will penetrate through them very quickly. Important factors that influence the treatment are the factors themselves in the development of cirrhosis.

After that, the specialist chooses a therapy, which may be as follows:

• The introduction of a liquid into the blood, which will contribute to the dissolution of irritant substances;
• Avoiding medications that can cause liver damage;
• Taking drugs that bind acids, bilirubin and other substances in the blood;
• Purpose of biliary and hepatoprotective drugs;
• In case of complications, laparoscopic or surgical intervention is likely, during which the specialist will remove the cause of the poor outflow of bile (for example, a stone).

No medicines will help if you do not follow the regimen and diet during treatment. In no case should you take alcohol, drugs and smoke. It is recommended to eat food 5 times a day in small portions. It is important to exclude fatty and spicy foods from the diet, the daily amount of animal fats consumed should not exceed 50 grams (this is approximately 10% of the daily norm, the remaining 90% are vegetable fats), reduce meat consumption as much as possible, replacing it with poultry or fish.

Useful for the body will be the use of drinking water in large volumes, freshly squeezed fruit juices. Tea, coffee and drinks with gas must be excluded.

Treatment of skin itching with cirrhosis of the liver will be more effective if you follow the rules of nutrition based on the diet "Table No. 5", which spares the diseased organ. Its author is Dr. M.I. Pevzner, who developed a complete diet with a limited amount of cholesterol and fats. The diet will be useful not only in the treatment of itching with cirrhosis, but also after getting rid of it.

Diet principles:

• The ratio of proteins-fats-carbohydrates should be 1:1:5;
• Drink a glass of water in the morning on an empty stomach;
• The average daily calorie intake is 2600;
• It is necessary to drink at least 1.8-2 liters of water per day;
• The amount of salt consumed per day should not exceed 10 grams (one heaping teaspoon).

Nutritional norms

For liver diseases, you need to use the following products:

• Compotes, rosehip broth, herbal teas;
• Dairy, vegetable, fruit soups;
• Cereals such as buckwheat, oatmeal, semolina and rice are boiled in water or with the addition of milk;
• The meat should be lean, taken in small quantities, you can eat poultry, rabbit meat;
• Boiled fish (hake, pike perch, tuna) should be consumed 2-3 times a week;
• Replace white bread with rye or breadcrumbs;
• Cheese and sour cream should be consumed infrequently, in small portions;
• You can low-fat kefir, milk, cottage cheese and yogurt;
• Vegetables containing starch will be useful.
• No more than two proteins and half the yolk of eggs per day;
• From the sweet, you can have a little marshmallow, sweets and marmalade without cocoa, jelly and jelly.

All food is either steamed or boiled or baked. You can not eat very hot and cold food.

If, following the doctor's instructions, a person managed to get rid of the problem described above, then do not forget about its cause - cirrhosis, which is more dangerous than this symptom.

In the early stages, this disease can be stopped, but only if it is properly and comprehensively treated. If the disease is detected later, then there are 2 options: slowing down the progression of cirrhosis and delaying complications, or liver transplantation, which is not suitable for every person and is quite expensive. healthy person recommended means of preventing cirrhosis of the liver, such as: personal hygiene, vaccination against viral hepatitis B, healthy and nutritious nutrition, smoking and alcohol cessation, treatment of any diseases only as prescribed by a specialist.

Irritation of the skin provides a person with physical and psychological discomfort. Doctors attribute this phenomenon to allergies. Itching may be the result of a disorder of the internal organs, in particular, the liver. It differs from the usual in a number of symptoms.

Liver disease leads to violations of the formation and excretion of bile from the body. When the ducts between the liver and pancreas are clogged, bile accumulates in the skin cells, and the person begins to suffer from jaundice. Bile acids irritate the skin endings, which causes itching. The intensity of the symptom depends on nervous system the patient and his sensitivity.

To get skin itching, a slight deviation in the composition of bile is enough, so it can be noticed before jaundice. Cirrhosis is characterized by the fact that the skin and whites of the eyes turn yellow during the disease. And irritation arises several years earlier.

With liver problems, sudden weight loss or jaundice occurs depending on the patient's weight, age, and other factors. If the irritation on the patient's skin suddenly disappears by itself, this is not always a favorable moment. The cessation of symptoms of itching suggests that the disease has passed into liver failure.

Reasons for the appearance

Itching that occurs on the body due to liver disease can be noticed in one place of the skin or throughout the body. The reason for its occurrence is:

1. The formation of stones in the bile ducts.
2. Cancer formations.
3. Various diseases of the organ, including hepatosis and toxic damage.
4. Cancer. The resulting neoplasms can disrupt the texture of blood vessels and cells.
5. Hepatosis is cholestatic. It occurs in pregnant women. Complications may arise due to high sensitivity to sex hormones.
6. Problems in the metabolic process. Such violations can lead to swelling and inflammation.

But liver problems can occur for the following reasons:

1. Alcohol use.
2. Taking antibiotics and drugs that affect the hormonal background.
3. Viral diseases.
4. poisonous substances.

It is important to pay attention to additional symptoms in order to quickly determine the cause of the disease.

What liver diseases are accompanied by itching?

Itching is associated with the entry into the blood of certain compounds that hepatocyte cells receive from bile acid. They are necessary for the human body to regulate the intestinal microflora and digestion. If the liver does not have any problems, then bile acid does not enter the bloodstream. Otherwise, things are different. Bile enters the bloodstream and irritates the nerve endings of the skin, which immediately contribute to the formation of itching.

If the patient has hepatic itching, yellow spots can be seen on the skin, these symptoms are added sharp pain in the right hypochondrium. The main difference between hepatic itching and allergic is that after taking antihistamines, irritation does not disappear.

Also, irritation on the skin can occur due to the following diseases of the organ:

1. cholestasis. The disease is characterized by impaired bile production. Often, with cholestasis in the liver, processes are formed associated with the replacement of hepatocytes with connective tissue. As a result, the patient may develop cirrhosis. Cholestasis develops from viral hepatitis and toxic poisoning of the organ. Sometimes skin irritation can occur after taking antibiotics. When the skin changes its color to a green tint, this disease is called subhepatic jaundice. In this case, the body begins to itch a lot. In addition to these symptoms, there may be sleep disturbance and nausea.
2. The occurrence of benign and malignant tumors. Cancer leads to the fact that there is a difficulty in the outflow of bile from the body. As a result of this, bile acid can not only enter the bloodstream, but also pass through other tissues, bypassing the liver.
3. Cholecystitis. This causes inflammation of the gallbladder, which later cannot function well. Because of this, stagnation of bile occurs and the formation of toxic elements in the liver, which are sent to the blood.
4. Hepatitis C. If severe itching appears with hepatitis C, which is an indicator of the acute phase of the disease, a rash occurs on the body, which itches very much. Sometimes with this disease, itching may not occur. Therefore, the patient turns to the doctor for help only when yellowness of the skin and a change in the color of feces and urine appear.
5. Biliary cirrhosis. With this disease, the destruction of liver cells appears. Often with cirrhosis, itching is the only symptom. It can often be seen on the legs and arms.

Change in the liver in biliary cirrhosis

Also, itching may appear due to problems with the absorption of substances that enter the tissues along with bile. Because of this, the body may not receive the necessary vitamins. Therefore, the skin becomes irritated and dry.

Differential Diagnosis

Itchy skin is not treated, as it is only a symptom of a serious illness. Previously, doctors are required to determine what problem of the liver or gallbladder bothers the patient, and only after that proceed with therapy. The sooner treatment begins, the less the patient will be bothered by itching.

To clarify the real disease, experts prescribe patients to undergo the following examinations:

• coagulogram;
• general and biochemical analysis blood;

Doctors choose a complex treatment. It allows you to qualitatively eliminate the cause that causes discomfort on the skin.

If a person suffers from itchy skin, he needs to listen to the following recommendations:

• refuse to visit the bath, sauna and hot tub;
• bathe in a cool shower in summer;
• give up alcohol and smoking;
• do not wear underwear made of synthetic materials;
• smear the skin with gels with a cooling effect;
• avoid emotional and physical stress;
• stop taking medications that cause irritation.

These tips can improve the patient's well-being.

Therapeutic measures from doctors

For patients who have itching of the body with liver diseases, doctors prescribe the following drugs:

1. Detoxification. Their main task is to purify the blood from harmful substances. Activated charcoal is considered to be a well-known medicine of this group.
2. Antiviral and antiseptic.
3. Antiphlogistic. They make it possible to stop the inflammatory process. Treatment of cholecystitis is carried out with drugs of this group.
4. Hepatoprotectors. Helps renew liver tissue and protect it from exposure to antibiotics or junk food.

Doctors treat hepatic ailment with the help of surgery and medication. If a patient may experience cholestasis on certain medications, then doctors cancel them.

Prevention of itching of the skin of the body in liver pathologies

So that patients never experience skin irritation, you need to take care of your liver. For this you need:

1. Avoid overheating of the skin.
2. Eat only approved foods.
3. Get rid of bad habits.
4. Restrict yourself from emotions that can lead to stress.
5. Drink drugs only after consulting with your doctor.

Summing up, it should be noted that itching in liver diseases is not specific, but a common symptom. First you need to find out what ailment caused it, and only after that carry out the necessary therapy.

Under cholestasis (cholestasis; Greek chole bile + stasis standing) is understood as a decrease or complete cessation of the outflow of bile due to a violation of its formation, excretion and / or excretion. Pathological process can be localized in any area from the sinusoidal membrane of the hepatocyte to the duodenal papilla.

Recall that the formation of bile occurs in several stages: 1) capture from the blood of a number of its components (bile acids, bilirubin, cholesterol, etc.) at the level of the basolateral membrane of hepatocytes; metabolism, as well as the synthesis of new components and their transport in the cytoplasm of hepatocytes; 2) secretion of bile through the canalicular (biliary) membrane of hepatocytes into the bile ducts; 3) further formation of bile in the biliary tract, and ultimately in the intestines.

In functional terms, cholestasis means a decrease in tubular bile flow, hepatic excretion of water and organic anions (bilirubin, bile acids). With severe cholestasis, there may be a "reverse flow" into the hepatocyte (and in most cases into the blood) of substances that should be excreted with bile. As a result, bile accumulates in hepatocytes and hypertrophied Kupffer cells (the so-called cellular bilirubinostasis) and in dilated canals (canalicular bilirubinostasis). With extrahepatic cholestasis, bile is located in the dilated interlobular bile ducts (ductular bilirubinostasis) and the liver parenchyma in the form of "bile lakes".

Cholestasis existing for several days causes potentially reversible ultrastructural changes. Persistent cholestasis with accompanying inflammation and reaction connective tissue leads to irreversible cholestasis, and after months/years to the development of biliary fibrosis and cirrhosis.

Classification and main causes of cholestasis. There are extra- and intrahepatic cholestasis (Table 1). In the first case, we are talking about obstructive jaundice, in which obstruction and / or mechanical damage to the extrahepatic bile ducts. Intrahepatic cholestasis is caused by a violation of the formation and transport of bile in hepatocytes or damage to the intrahepatic bile ducts (or a combination of these mechanisms). Intrahepatic cholestasis is divided into intralobular cholestasis, caused by damage to hepatocytes (hepatocellular) and tubules (canalicular), and extralobular (ductular), associated with damage to the intrahepatic bile ducts.

The pathogenesis of cholestasis in mechanical obstruction is obvious and does not require detailed consideration.

As for intrahepatic cholestasis, its development is multifactorial. Its main causes and mechanisms of development are presented in Table. 2.

As can be seen from Table. 2, the pathogenesis of intrahepatic cholestasis is multifactorial:

• dysfunction of the basolateral, sinusoidal and canalicular membranes. This phenomenon may be based on disorders of hepatobiliary transport, such as mutations in the genes of transporter proteins and acquired dysfunctions of transport systems, causing a violation of canalicular or cholangiocellular secretion;
• changes in the composition and fluidity of hepatocyte plasma membranes affect the activity of enzymes and receptors. Membrane fluidity is determined by the ratio of phospholipids to cholesterol. Reduced membrane fluidity is usually associated with elevated cholesterol, which occurs with drug-induced cholestasis (estrogens, anabolic steroids);
• violation of the cytoskeleton of hepatocytes, which lead to the disappearance of microvilli on the apical surface of hepatocytes, a decrease in the contractility of the canalicular membrane, and can also cause increased permeability of intercellular tight junctions and lead to a reverse flow of bile into the sinusoids; detergent action of bile acids, the accumulation of which leads to damage to cell membranes, accumulation of cytosolic calcium, activation of intracellular hydrolases and necrosis of hepatocytes. Bile acids inhibit hepatocyte regeneration, activate fibrogenesis, induce the expression of class III antigens of the major histocompatibility complex, predisposing to the development of autoimmune damage. In addition, they contribute to the accumulation of free radicals, which, in turn, trigger the activation of caspases, which ultimately leads to apoptosis of biliary epithelial cells.

Note that most of the above factors lead to a decrease in the activity of S-adenosylmethylsynthetase, as a result of which the production of S-ademetionine is disrupted. The latter aggravates the course of biochemical processes in the hepatocyte; in hepatocellular membranes, the content of phospholipids decreases, the activity of Na + -K + -ATPase and other carrier proteins decreases, which also affects membrane fluidity, capture and excretion of bile components. Reduced cellular reserves of thiols and sulfates (glutathione, taurine, etc.), which are the main detoxification substances, and also have a pronounced antioxidant effect. Their deficiency ultimately leads to cytolysis of hepatocytes in cholestasis of any genesis.

Clinical manifestations cholestasis are of the same type and do not depend on the etiology and mechanisms of its development. They are caused by the following factors: 1) a decrease in the amount or absence of bile in the intestine; 2) excessive intake of bile elements into the blood; 3) the impact of bile components on the liver cells and tubules.

Main clinical symptom cholestasis is considered pruritus, which does not always occur. With a combination of cholestasis with jaundice, there may be a corresponding color of the skin, darkening of the urine and a change in the color of the feces. On the skin of patients, in addition to traces of scratching (companions of skin itching), you can see other markers of cholestasis: dryness, hyperpigmentation, xanthomas and xanthelasma. Long-term cholestasis, accompanied by steatorrhea, leads to impaired absorption of fats with the development of a deficiency of fat-soluble vitamins, most often expressed in the development of hepatic osteodystrophy.

With the formation of biliary cirrhosis, there are also signs of portal hypertension and hepatocellular insufficiency. Hepatocellular insufficiency develops on average 3-5 years after the onset of cholestatic jaundice. In some diseases (such as primary biliary cirrhosis), portal hypertension may precede the formation of cirrhosis, forming according to a presinusoidal mechanism.

Laboratory diagnosis of cholestasis is aimed at identifying bile components in the blood serum or signs of damage to the canalicular membranes of hepatocytes or biliary epithelium.

Laboratory markers of cholestasis are: alkaline phosphatase (biliary isoenzyme), leucine aminopeptidase, gamma-glutamyl transpeptidase, 5'-nucleotidase. There may also be an increase in bile acids, bilirubin, cholesterol.

Consider the main directions of therapy, surgical treatment and non-drug effects on cholestasis and its consequences.

diet therapy

Deficiency of bile salts in the intestinal lumen dictates the characteristics of the diet for cholestasis. Along with adequate protein and calorie intake, patients are advised to limit fat to 40 g/day. If necessary, the fat component of the food can be replenished with enteral mixtures containing medium chain triglycerides, which are digested and absorbed in the intestine even in the absence of bile acids. Steatorrhea determines the need for food enrichment with fat-soluble vitamins and calcium (or an additional prescription in the form of medicines) . There are recommendations to limit copper intake as it accumulates in liver cholestasis, but these are highly controversial.

Etiological treatment

Etiotropic therapy has been developed for a limited number of hepatic diseases, usually infectious. If we talk about predominantly cholestatic diseases, then success is undeniable. surgical interventions aimed at decompression of the biliary system.

Biliary decompression

Both laparoscopic and laparotomic operations still do not lose their relevance. Gradually, with the development of minimally invasive technologies, the frequency of "big" operations is decreasing. After all, a major operation is a more serious injury to the body; in addition, endoscopic methods retain the possibility for repeated, including minimally invasive interventions. Therefore, in most cases, our European and American colleagues consider endoscopic methods of treating obstructive jaundice as first-line methods. With their help, for example, it is possible to resolve up to 94% of cases of obstruction of the bile ducts caused by various causes.

In clinics where a large number of endobiliary interventions are performed (according to European studies - more than 40 per year), the percentage of complications is significantly lower than in centers that perform fewer manipulations.

The choice of method for eliminating obstruction of the bile ducts depends on the cause that caused jaundice. In principle, the following methods of endoscopic assistance can be distinguished:

Let's take a look at the capabilities of each method.

Papilectomy is used for benign formations OBD that caused a violation of the outflow from the bile or pancreatic ducts or have a high risk of malignancy. After removal of the BDS, stenting of the choledochus and the main pancreatic duct is performed to prevent swelling of the mouths and the development of cicatricial stenosis.

Stricture dissection is used in cases where a benign non-tumor stricture is located in the terminal section of the ducts, not higher than the intramural part. In fact, an endoscopic papillosphykterotomy (EPST) is performed, which can be performed in a standard way, after pre-dissection, or in the form of suprapapillary choledochotomy. If it is not possible to cannulate the choledochus directly through the mouth, predissection of the BDS from the mouth is performed using an end (needle) papillotome. This technique is more dangerous and difficult to perform, especially for novice endoscopists.

In some cases, when the stricture is at the level of the orifice of the OBD or its ampulla, the upper part of the longitudinal fold may bulge. In these cases, a dissection of the protruding part is performed, without dissection directly of the mouth of the OBD. This technique is called suprapapillary choledochotomy.

Almost any therapeutic manipulation on the bile ducts, especially if it is planned to repeat manipulations (for example, to replace stents), begins with facilitating subsequent access, that is, performing EPST.

Sometimes, most often with cholelithiasis, the cause of jaundice can be completely eliminated. Lithoextraction can be performed using a fairly large number of endoscopic instruments. If the calculus is large, then its lithotripsy is preliminarily performed. More exclusive treatments for choledocholithiasis include laser lithotripsy and electrohydraulic lithotripsy. These techniques are used during cholangioscopy. However, they are rarely used in routine clinical practice due to their high labor intensity and high cost. According to our data, more than 96% of stones, even large ones, can be removed endoscopically. To date big size calculus is not a contraindication for endoscopic lithoextraction.

If the stricture is located above the intramural part of the common bile duct, its expansion is required. For this, two methods are used in endoscopy: balloon dilatation and bougienage. Depending on the genesis of the stricture, its dilatation may be the final or staged treatment. In most cases, with benign strictures (stricture of the choledochocholedochal anastomosis, biliodigestive anastomosis, after choledochotomy, ischemic strictures in patients after liver transplantation), several dilation sessions are required within 1-2 years. In this case, between manipulations, temporary endobiliary stents are installed in the stricture area to prevent their narrowing.

In malignant strictures, dilatation can be performed as a step in stent manipulation or photodynamic therapy.

Stenting of the bile ducts is performed with plastic or nitinol stents. Both types have their advantages and disadvantages.

Plastic stents are quickly clogged with thick bile contents within 2-5 months. Blockage of the stents again leads to an increase in jaundice and the development of cholangitis. On the other hand, these stents are easily removed and can be replaced with new ones. Recanalization of plastic stents is possible but not advisable.

Nitinol (metal) self-expanding stents come in coated and uncoated versions. These stents can last much longer than plastic stents (up to 1-2 years), but their removal and replacement can be much more difficult. Self-expanding stent placement may be recommended in patients with a poor prognosis who have an expected life expectancy of less than 1 year ( metastatic lesion gates of the liver, inoperable tumors of the pancreas and bile ducts). Another disadvantage of nitinol stents is their high cost.

Photodynamic therapy is a method of intravenous administration a photosensitizer that selectively accumulates in tumor tissues. As a result, the volume of education decreases, blockage of the bile ducts is eliminated. The effectiveness and safety of this method in cholangiocarcinoma has been proven. The technique is very time-consuming and expensive, therefore, it has not yet found wide application in clinical practice in Russian Federation.

With the development of endoscopic ultrasonography (EUS), therapeutic puncture methods are also developed, performed under the control of endoscopic ultrasound. So, to eliminate obstructive jaundice, the literature describes methods of choledocho- and cholestomy under the control of endoscopic EUS. The method consists in puncture under ultrasound control of dilated bile ducts or gallbladder through the wall of the duodenum or stomach, followed by their stenting. In fact, bilidigestive anastomoses are formed.

There are situations when the choledochus is squeezed by a pancreatic cyst. In this case, EUS-guided drainage of the cyst can be performed.

A brief review of endoscopic methods for the diagnosis and treatment of obstructive jaundice shows significant progress in this direction in recent years.

Pathogenetic therapy

Ursodeoxycholic acid (UDCA). UDCA is the only conventional drug for the treatment of most chronic cholestatic diseases. The ability to treat cholestasis is considered the most valuable property of this drug.

UDCA competes with toxic bile acids for absorption into small intestine, as well as on the membrane of hepatocytes and cholangiocytes. It is believed that the positive effect of UDCA on the course of chronic cholestasis is primarily associated with a decrease in damage to cholangiocytes by toxic bile acids (by suppressing their secretion and reducing the pool by reducing their absorption in the ileum).

In addition, UDCA stimulates the transport of bile acids and organic anions in hepatocytes and cholangiocytes. It affects a number of processes associated with hepatocyte transporter proteins: their transcriptional regulation; inclusion in the apical membrane; phosphorylation and dephosphorylation at sites of action; and also affects the processes of exocytosis (by activating calcium-dependent alpha-protein kinase) and the expression of transport systems in the biliary epithelium (bicarbonate choleresis).

Actually, the cytoprotective effect of UDCA in cholestasis is determined by its ability, forming double molecules interacting with lipophilic membrane structures, to integrate into the cell membrane, increasing the resistance to toxic effects of hepatocytes, cholangiocytes and epithelial cells of the gastrointestinal tract.

The immunomodulating properties of UDCA are mainly due to a decrease in the pool of toxic bile acids, which, during cholestasis, induce the expression of class I and II HLA molecules on the membranes of hepatocytes and cholangiocytes, which contributes to their recognition with subsequent destruction by cytotoxic T-lymphocytes. Long-term use of UDCA inhibits the expression of HLA antigens on the membranes of hepatocytes and cholangiocytes, normalizes the activity of cytotoxic T-lymphocytes, affects the expression of dipeptidyl peptidase-4 and the formation of interleukin-2, reduces the elevated content of eosinophils, reduces the synthesis of immunocompetent IgM in combination with a decrease in the production of autoantibodies.

Additional mechanisms of action of UDCA can be inhibition of apoptosis of cholangiocytes and hepatocytes (primarily affecting the release of cytochrome C from mitochondria into the cytosol and triggering the caspase cascade) and antioxidant properties, changes in the metabolism of prostaglandins and fatty acids, and effects on liver regeneration.

The antifibrotic effect of UDCA is due to a decrease in the content of fibrogenesis activators and a direct inhibition of the activity of stellate cells. The influence of UDCA on the induction of cytochrome CYP3A4 is proposed, which should be important for the metabolism of bile acids and many xenobiotics.

The variety of effects of UDCA determines a significant decrease in the progression of fibrosis in a number of liver diseases.

Most convincingly proven positive action UDCA in such a truly cholestatic disease as primary biliary cirrhosis. In a combined analysis of French, Canadian, and North American patient cohorts at 2-4 years of follow-up, there was a reduction in mortality and the need for liver transplantation in groups with moderate and severe disease. The "Barcelona" study of 192 patients treated with UDCA for a period of 1.5-14 years showed that the survival of "responders" to UDCA (the response was assessed by the level of reduction alkaline phosphatase) was higher than predicted by the Mayo predictive model and corresponded to the population .

The dose of UDCA 13-15 mg/kg/day in most cholestatic diseases has an advantage in biochemical response and cost in comparison with low and high doses. An exception is cystic fibrosis, where doses of 20–30 mg/kg/day are recommended. In primary sclerosing cholangitis, recommended doses have not been determined.

There is evidence of a positive effect of UDCA on drug-induced cholestasis, including that caused by one of the most commonly causing hepatotoxicity drugs - amoxicillin / clavunate.

The European Association for the Study of Liver Diseases (EASL, 2009) in the treatment of cholestatic diseases recommends the mandatory appointment of UDCA as a basic therapy for a number of liver diseases: primary biliary cirrhosis, primary sclerosing cholangitis, cystic fibrosis, progressive familial cholestasis type 3 (PFIC 3), intrahepatic cholestasis of pregnancy and discusses its use in drug-induced cholestasis and benign familial cholestasis.

For today original drug UDKhK - Urso (Japan) is absent in Russia. In this situation, when choosing generic drugs that are widely represented on the domestic pharmaceutical market, one should be guided primarily by the "price / quality" ratio. Appeared in last years According to our clinical impressions, domestic drug UDCA Urdoksa is not inferior to generic forms previously registered in our country.

S-adenosyl-L-methionine (SAMe) also used in a number of liver diseases as an anticholestatic agent. Its participation in the processes of sulfation, including bile acids and taurine, leads to a decrease in the pool of toxic free bile acids, which improves their removal from the hepatocyte and promotes their elimination by the kidneys. Participation in the synthesis of structural proteins and phospholipids ensures the stabilization of cell membranes and mitochondria and thereby improves the functioning of transport systems. There is experimental evidence that SAMe reduces bile acid-induced apoptosis, although to a lesser extent than UDCA.

The effectiveness of SAMe has been shown in patients with chronic cholestasis of various origins. In randomized clinical trials, it has demonstrated the ability to increase the life expectancy of patients with alcoholic cirrhosis of the liver. EASL (2009) discusses its use in intrahepatic cholestasis of pregnancy as a second-line agent. In experimental work, SAMe prevented estrogen-induced cholestasis. In a randomized study including 72 patients with psoriasis, the ability of SAMe to prevent the hepatotoxic effect of cyclosporine A, which inhibits the transport of bile acids and reduces biliary glutathione, has been shown. The antidepressant effect of SAMe is determined by an increase in the level of serotonin, which can bring it closer in effects to sertraline used in cholestasis-induced pruritus.

Glucocorticosteroids (GCS) reduce the level of bilirubin in hepatocellular jaundice (prednisolone test), but do not affect cholestasis itself. Their administration may reduce symptoms such as itchy skin. At the same time, taking corticosteroids leads to a sharp decrease in bone mineral density, increasing the risk of developing osteoporosis, and also increases the risk of developing other adverse events.

Nuclear receptor agonists. In 2011, the success of a Phase II clinical trial of a new class of drug, Obeticholic Acid (INT-747), a Farnesoid X receptor (FXR) agonist, was announced. Monotherapy with this drug in 59 patients with primary biliary cirrhosis for 12 weeks resulted in a significant decrease in alkaline phosphatase compared with placebo. This is the most likely candidate for the new effective drug in the treatment of primary biliary cirrhosis.

Liver transplant remains the only method of treating patients with a progressive course of the disease and the development of hepatic decompensation or malignancy. In the earlier stages of chronic cholestatic disease, disabling weakness, resistant pruritus, and severe osteoporosis may be considered as indications for inclusion on the waiting list.

Treatment of extrahepatic manifestations

The main extrahepatic manifestations of cholestasis are fatigue and pruritus.

Treatment of pruritus. The European and American Association for the Study of Liver Diseases are unanimous in the choice of drugs for the treatment of cholestatic pruritus.

Line I: bile acid sequestrants (cholestyramine - 4 g 4 times / day).

II line: rifampicin (150-300 mg/day with a possible dose increase to 600 mg/day).

III line: oral opiate antagonists (naltrexone 50 mg/day).

IV line: sertraline (75-100 mg/day).

Bile acid sequestrants (cholestyramine) have been used for many decades, although, as for most "old" drugs, there is no decent evidence base for their use. In the Russian Federation, cholestyramine, unfortunately, has not been available in recent years.

Rifampicin is an inducer of pregnane X-receptors that regulate the biosynthesis, detoxification, and transport of toxic bile acids; therefore, in cholestasis, rifampicin may have not only a symptomatic, but also a pathogenetic effect. The effectiveness of rifampicin is maintained even with long-term use (2 years). Cases of rifampicin hepatotoxicity in cholestatic liver disease are relatively rare. However, its appointment requires mandatory biochemical monitoring of liver parameters.

Oral opiate antagonists (Naltrexone) seem to act on itch by reducing opioidergic neurotransmission, and the selective serotonin reuptake inhibitor Sertraline is thought to affect itch perception.

Antihistamines, phenobarbiturates, and ondansetron are no longer recommended for the treatment of cholestatic pruritus due to poor efficacy and side effects.

Other possible methods of relief of itching include extracorporeal techniques: albumin dialysis, plasmapheresis.

Physiotherapy: ultraviolet irradiation for 9-12 minutes daily in some cases can reduce itching and hyperpigmentation.

Fatigue, which increases with the progression of the disease, is one of the important problems in a number of cholestatic diseases. There is currently no specific therapy for its treatment.

In order to reduce fatigue, EASL recommends treatment of comorbid conditions (hypothyroidism, anemia, diabetes, depression), exclusion of factors contributing to autonomic dysfunction and sleep disturbances (excessive prescription of antihypertensive drugs, evening caffeine use), the use of psychological support methods.

The use of modafinil (an analeptic originally developed for the treatment of narcolepsy), used in pilot studies for the treatment of fatigue in primary biliary cirrhosis, appears promising.

Treatment of complications of chronic cholestasis

Fat-soluble vitamin deficiency and osteoporosis are specific complication of chronic cholestatic diseases.

Osteoporosis. Prevention of osteoporosis implies, first of all, the exclusion of additional risk factors for its development (smoking, low physical activity, etc.), hormone replacement of postmenopausal women.

Traditionally, in chronic cholestasis, the constant use of calcium (1000-1200 mg / day) and vitamin D (400-800 IU / day) is recommended, although the effectiveness of this has not been proven by EASL. With severe bone pain, course parenteral administration of calcium gluconate at a dose of 15 mg / kg per day can be effective.

With the development of severe osteoporosis, and even more so spontaneous fractures, bisphosphonates are recommended, primarily Alendronate, for the effectiveness of which there is a sufficient evidence base. There are also data on the use of parenteral bisphosphonates. The results of the use of sodium fluoride and selective estrogen receptor modulator raloxifene in hepatogenic osteoporosis are limited and controversial.

Deficiency of fat-soluble vitamins. The administration of vitamin D is considered primarily as the prevention of osteoporosis. Oral administration of vitamins A, E and K is recommended, as a rule, with clinically significant steatorrhea or with a decrease in their concentrations in the blood. Parenteral forms of vitamin K are prescribed for the prevention of bleeding (for example, during invasive procedures on the background of cholestasis).

In conclusion, let us say that a deep understanding of the mechanisms of development of cholestasis and identification of its causes can serve as a key in the therapeutic and/or surgical tactics of managing this category of patients.

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A. Yu. Baranovsky*, doctor of medical sciences, professor
K. L. Reichelson*,
N. V. Semenov*,Candidate of Medical Sciences, Associate Professor
E. G. Solonitsin**, Candidate of Medical Sciences

*GBOU VPO SZGMU them. I. I. Mechnikova of the Ministry of Health and Social Development of Russia,
**FGBU GKB No. 122 im. L. G. Sokolova FMBA of Russia, Saint Petersburg