Recommendations for the diagnosis and treatment of cirrhosis of the liver. Symptoms and treatment of primary and secondary biliary cirrhosis of the liver. Factors and risk groups

Further management of the patient

After discharge, all patients are subject to dispensary observation on an outpatient basis.
At each visit to the doctor, the need for laboratory and instrumental examination should be assessed to detect ascites, spontaneous bacterial peritonitis, internal bleeding, hepatic encephalopathy, and hepatorenal syndrome. It is also necessary to assess patient compliance with all medical recommendations, identify possible side effects of drug therapy.
FEGDS is performed at intervals of 3 years if no varicose nodes are detected during the first examination, and 1 year if small varicose nodes are visible. After successful endoscopic ligation of the nodes, FEGDS is repeated after 3 months, and subsequently every 6 months.
All patients with cirrhosis of the liver should be vaccinated against viral hepatitis A and BB.
All patients with cirrhosis of the liver should be screened for hepatocellular carcinoma every 6 months: ultrasound of the liver and determination of the concentration of α-fetoprotein B in the blood.
■ Portal hypertension and bleeding from varices: Bleeding from esophageal and gastric varices is associated with a high mortalityA, which dictates the need for preventive measures.
aza after establishing the diagnosis of liver cirrhosis, it is mandatory to perform FEGDS to assess the severity of varicose veins.
■ Ascites: measures are shown to slow the progression of edematous-ascitic syndrome. Timely detection of hyponatremia and renal failure is also necessary.
✧ It is necessary to weigh the patient and measure the circumference of the abdomen at each visit to the doctor.
✧ Serum potassium, sodium, residual nitrogen, creatinine should be determined annually or more frequently if necessary (eg, if fluid retention is suspected with excessive diuretic therapy).
✧ Limiting salt intake to 1–3 g/dayA.
✧ Restriction of fluid intake in the presence of hyponatremia (sodium concentration less than 120 mmol / l).
■ Hepatic encephalopathy: for successful treatment, it is necessary to eliminate provoking factors and correct the disorders caused by them.
✧ Reasons. Provoking factors include the following:
- bleeding from varicose veins of the esophagus;
- taking sedatives and tranquilizers;
- massive diuretic therapy;
- alcohol consumption;
- infectious complications;
– surgeries of imposing a porto-caval anastomosis;
- excessive consumption of animal proteins;
- surgical interventions for other diseases;
- laparocentesis with the removal of a large amount of ascitic fluid without additional administration of albumin.
✧ Prevention.
take measures aimed at preventing hepatic encephalopathy.
- Primary (in the absence of bleeding in history) and secondary (if they are present in history) prevention of bleeding from varicose veins of the esophagus and stomach.
- In case of developed bleeding, antibiotics are indicated to prevent spontaneous bacterial peritonitis and sepsis.
– Prevention of spontaneous bacterial peritonitis.
– Prevention of constipation, preferably with small doses of lactulose. The dose of lactulose should be selected in such a way as to achieve soft stools 2-3 times a day. Usually the dose is from 30 to 120 ml / day.
– Exclusion of sedative drugs and narcotic analgesics.
- Prevention of liver dysfunction and electrolyte disorders: renal failure, metabolic alkalosis, hypokalemia, dehydration, excessive diuretic effect.
■ Infectious complications (primarily spontaneous bacterial peritonitis) with ascites often develop, and therefore there is a need for their prevention.
Signs of infection may be an increase in body temperature and abdominal pain. For the prevention of bacterial infection in hospitalized patients with ascites, the appointment of long-acting fluoroquinolones is indicated in the following cases:
✧ protein concentration in ascitic fluid is less than 1 g/l;
✧ bleeding from varicose veins of the esophagus and stomach A (infectious complications develop in 20% of patients within 2 days after the onset of bleeding; within 1 week of hospital stay, the frequency of bacterial complications increases to 53% B);
✧ a history of spontaneous bacterial peritonitis.
■ Renal failure: diagnosed with an increase in serum creatinine concentration of more than 132 µmol / l (1.5 mg%) and a decrease in daily diuresis. To establish the diagnosis of hepatorenal syndrome, it is necessary to examine the urinary sediment, in which there should be no changes. Timely prevention is needed.
✧ At each visit to the doctor, the patient's compliance with the regimen of taking all prescribed drugs should be assessed.
✧ Nephrotoxic drugs such as aminoglycosides and NSAIDs should be avoided. Also, ACE inhibitors, β-lactam antibiotics, sulfonamides, rifampicin, diuretics can have a nephrotoxic effect.
Causes of decompensation
Among the factors underlying the decompensation of cirrhosis, the following can be distinguished:
■ non-compliance with the diet: increased salt load;
■ violation of the dose and mode of taking drugs;
■ drinking alcohol;
■ iatrogenic factors: saline infusions, etc.;
■ gastrointestinal bleeding;
■ development of hepatocellular carcinoma;
■ infectious complications;
■ portal vein thrombosis.

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Symptoms and characteristics of liver cirrhosis

In modern medicine, cirrhosis of the liver is understood as the replacement of normal hepatic tissue with fibrous tissue, with the formation of many nodes, leading to complete dysfunction of this organ. Among the main signs of incipient cirrhosis, experts distinguish the occurrence of fever, nausea, vomiting with blood, diarrhea and constipation, severe pain in the abdomen. When contacting a doctor with these symptoms, a specialist can diagnose a patient with alcoholic encephalopathy, septic shock, muscle stiffness, oliguria, and irritability of the peritoneal region.

There are cirrhosis of the liver for various reasons. Very often, prolonged alcoholism leads to the development of this anomaly, which first causes various defective conditions of the liver, bleeding of the gastrointestinal tract, leads to hepatitis B, C and D. Cirrhosis can also be caused by infectious processes in the urinary system and medical manipulations in it. The disease also occurs with sexual infections, weakened immunity, in case of detection of a high protein norm in the body, with metabolic disorders, diseases of the gallbladder.

Due to the specific nature of the symptoms of cirrhosis and its often unexpressed signs, an accurate diagnosis is carried out using special studies and analyzes. The first signs, in the event of which a doctor may suspect cirrhosis in a patient, may be severe pain in the liver, the presence of diagnosed leukocytosis, bleeding in the gastrointestinal tract, and fever. Also, this symptomatology may indicate peritonitis that has arisen, which will require immediate hospitalization and surgical intervention.

It is important to understand that the development of cirrhosis is a rather lengthy and often asymptomatic process. So, with alcoholism, the first symptoms may begin to appear only after 10 years of regular drinking. However, after the symptoms become apparent, it will be very difficult to treat cirrhosis of the liver. Most often, to successfully overcome the disease, transplantation of the affected organ will be required.

Preventive measures for cirrhosis

If a patient has prerequisites for the occurrence of cirrhosis of the liver (for example, frequent alcoholism or hepatitis), doctors recommend that he undergo diagnostics in order to detect the disease at an early stage, as well as to be able to treat it. Among the main methods that prevent the development of cirrhosis, we can distinguish:

• screening for excessive alcohol consumption, which almost always accelerates the development of cirrhosis;
• a hemochromatic study that demonstrates a high content of iron in the plasma and determines the binding ability of the patient's blood.

If a specialist suspects that a patient suffers from alcoholism, GAGE ​​testing is sometimes used to confirm this fact, in which the patient answers the question whether he felt a desire to reduce alcohol consumption, whether his remark irritates someone close about the fact that it's time to stop drinking, whether he feels guilty about his own alcoholism. With two positive answers to these questions, the doctor can diagnose alcoholism in the patient.

To prevent cirrhosis of the liver, it is sometimes necessary to do screenings for the presence of hepatitis B and C, since this disease entails cirrhosis, but it is possible to cure both pathologies only in the early stages. Also, when prescribing hepatotoxic drugs to patients, doctors regularly (every 3 months) screen the liver. Screenings are also indicated for those who have had cases of liver disease among close relatives. In this state of affairs, the study revealed the concentration of ferritin, deficiency of a-1-antitrypsin and the volume of ceruloplasmin.

Also, liver diseases are prevented in those patients who are obese. The risk of getting this disease is in those suffering from diabetes mellitus or hyperlipidemia. Such patients often undergo an ultrasound examination, during which the presence of steatosis, which negatively affects the liver, is revealed.

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What is cirrhosis of the liver and what are the clinical symptoms

Cirrhosis of the liver is a kind of diffuse process, which is characterized by fibrosis with the formation of nodes. It is the last stage after chronic ailments.

Symptoms

The signs of the disease are:

1. Fever.
2. Hepatic encephalopathy.
3. Irritation of the peritoneum.
4. Rigidity of the muscles.
5. Vomit.
6. Diarrhea.
7. Septic shock.
8. Tachycardia.
9. Oliguria.
10. Severe pain in the abdomen.

The reasons

Such factors influence the development of this disease:

• Severe liver defects.
• Bleeding in the gastrointestinal tract.
• Urinary system infection.
• Medical manipulations in the urinary system (catheter placement).
• High protein content.
• Hepatitis C, D, B.
• The use of alcoholic beverages.
• Problems in the immune system.
• Diseases of the biliary tract.
• Wrong metabolism.
• Sexual infections.
• Hypervitaminosis.

Due to the fact that the symptoms of this disease are very specific, the diagnosis can be made only after the study of AF. Indications for the study are the following symptoms: pain in the abdomen, leukocytosis, fever, stomach bleeding. Sometimes such symptoms say that it is not cirrhosis, but peritonitis. In this case, the patient needs urgent surgery.

Liver cirrhosis does not develop immediately, for example, if a person develops it due to alcohol dependence, his symptoms will begin to bother the patient after 10–12 years of alcohol consumption.

Disease prevention

Prevention primarily includes the timely detection of the disease and the correct correction of acquired disorders.

Here are some methods by which you can prevent the development of the disease.

• Hemochromatosis. This study is aimed at identifying hemochromatosis. During the study, specialists determine the amount of iron in the plasma, the total binding capacity of the blood. If these figures are too high, then a second study will have to be carried out to confirm this fact.
• Screening for excessive drinking has been found to limit alcohol consumption to reduce the likelihood of disease.

In some cases, doctors use GAGE ​​- tests that have such important questions:

1. Have you ever felt like it was time to limit your alcohol consumption?
2. Did you get annoyed when you were told that it was time to stop drinking?
3. Have you ever felt guilty about your drinking?

Sensitivity is approximately 80%, the main advantage is the test during the history taking.

If there are two affirmative answers to the above questions, this is the basis that a person really has an alcohol addiction.

• Screening for hepatitis C and B. Some patients require special testing for the presence of hepatitis viruses. The survival rate of patients with this diagnosis is very high if a person seeks help in a timely manner.
• Screening while on certain hepatotoxic drugs such as amiodarone C and methotrexate B. They set AST and ALT about once every three months.
• Screening among all relatives and relatives of patients with chronic liver damage. As a rule, the closest relatives are checked first, the concentration of ferritin, ceruloplasmin, and a1-antitrypsin deficiency are detected.
• Screening to detect liver disease due to fatty deposits. Risk factors inherent primarily in people suffering from diabetes, obesity, hyperlipidemia. All people in this risk group should have an ultrasound to detect steatosis. Doctors usually warn patients about the likelihood of liver complications.

What is the treatment

Therapy of the disease is usually aimed at the following:

1. Slows down the progression of this disease.
2. Reducing clinical manifestations.
3. Increased lifespan.
4. Antifibrotic therapy.
5. Maintaining nutritional status.
6. Prevention of complications.
7. Treatment of emerging complications.

Treatment for this disease is different, if it has not yet developed, then doctors choose a non-drug method of therapy. It consists of adherence to the regimen and correct nutrition. As a rule, with such a diagnosis, doctors prohibit physical activity. At each appointment, the specialist must measure the circumference of the abdomen.

Quite often, with such a diagnosis, it is advised to follow a diet as a recommendation.

• The diet of the patient should be dominated by carbohydrates 70%, fats 30%. Such a diet will not allow the development of cachexia.
• With a complicated type of disease, there should be more carbohydrates, somewhere between 75 and 25% fat. Such a diet is aimed primarily at restoring nutritional status.
• In the severe stage of encephalopathy, the intake of proteins should be limited to 30 grams per day.
• Be sure to prescribe a complex of multivitamins with such a disease.
• People suffering from alcohol addiction are additionally prescribed thiamine.
• You should reduce the intake of foods that have iron in their composition.
• Complete refusal of alcohol increases the chances of recovery.

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Therapy for cirrhosis

If the patient is being treated in a hospital, then special treatment is applied to him. In the beginning, the doctor relieves the patient of everything that can aggravate the condition of the liver, namely:

• Eliminates alcohol from life
• From improper hepatitis therapy,
• From any kind of toxins.

The patient is assigned bed rest and is not allowed to overload his body. Due to this, blood circulation is normalized, and the liver begins to function normally.

Little of, the patient is ordered to follow a diet with cirrhosis of the liver, this diet does not allow you to eat a lot of protein. Also, a person needs to limit himself in taking salt and fried foods.

In addition to these measures, the patient is prescribed:

• Preparations that renew the liver and have a positive effect on metabolism.
• Blood transfusion to increase platelet count. Such a procedure is necessary, with such a complication as ascites.
• Take glucocorticoid hormones if the pathology progresses.

Specialists conduct detoxification to the patient to remove toxins from the body and prevent them from being absorbed into the intestines. To cleanse the gastrointestinal tract, the patient must drink activated charcoal.

Treatment for complications of pathology

Very often, the patient is taken to the hospital, with such a complication as ascites. Ascites is an accumulation of excess fluid in the body, which causes a person's stomach to grow rapidly. The hospital determines the cause of ascites.

To begin with, specialists take a blood test and check the condition of the liver. The patient is immediately prescribed a diet and bed rest. In the diet, experts reduce the intake of fats and proteins.

When a person in the gastrointestinal tract stops bleeding, then the doctor prescribes taking drugs that promote rapid blood clotting. Also, the patient is given droppers with such substances: calcium chloride, epsilon aminocaproic acid and vikasol. Only with a severe hemorrhage is a person given a blood transfusion to repair the damage.

To stop bleeding, doctors use methods such as:

1. gastric hypothermia,
2. balloon tamponade,
3. Bandaging of bleeding wounds.

Carrying out such procedures, the patient's body is depleted, so a tube is installed in the esophagus through which the patient receives glucose, liquid and other useful substances. When it is removed, the patient is given dietary and light food.

What to do during hepatic coma?

With complicated cirrhosis, the patient is carefully monitored, as he may develop a hepatic coma. It can be noticed if the patient has an unpleasant odor coming from the mouth.

If the patient is in this condition, then the medical staff measures the level of potassium in the blood every 24 hours and all indicators of the state of the liver are measured. This is done in order to understand how to treat the patient.

Being in a state of precoma, the patient is injected with calories through an umbrella into the stomach, due to which the body continues to function normally. Moreover, the amount of protein consumed is minimized.

After the patient has recovered from this state, doctors are allowed to increase protein intake. Specialists do not leave such a patient and monitor his condition.

If a person is in a coma, then he receives all the necessary substances and medicines through a dropper.

Surgical intervention

Surgical intervention is used in extreme cases, since after such an operation, the work of the organ can be severely disrupted and lead to death.

Surgeons can do an organ transplant. The scale of such an operation depends on how damaged the organ is. Doctors do a full or partial liver transplant.

However, the operation is contraindicated for patients who are over 55 years old and those who have pronounced jaundice.

Before performing the operation, the doctor examines the patient's condition in detail to determine whether the patient will undergo surgery or not. In order to prevent pathology from reaching such a state, try to take this disease seriously.

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What is pathology?

Biliary cirrhosis is a very rare form of pathology, so it is not always possible to quickly make a correct diagnosis. In most cases, the disease is asymptomatic for a long time and is discovered by chance, during medical examination or during the diagnosis of other diseases. Symptoms of biliary cirrhosis usually occur when the disease goes into a severe stage, and apart from organ transplantation, the patient can no longer be helped.

Biliary cirrhosis is characterized by the replacement of healthy tissue with fibrous tissue. This occurs when the affected parenchyma cells are unable to cope with their functions.

The more liver cells are affected, the more pronounced liver failure becomes and the higher the likelihood of complications: portal hypertension, ascites and damage to other internal organs.

Life expectancy with such a diagnosis directly depends on the stage at which the disease was detected. Cases have been registered when patients were unaware of pathological liver damage for two decades, and the rapid development of the disease is also known, when a fatal outcome occurred within 2-3 years after the onset of cirrhosis.

Moreover, the rate of development of the disease and the growth of fibrous tissue in each patient is different and depends on many factors: the state of the immune system, the age of the patient, his lifestyle and the presence of concomitant diseases. It is possible to predict the development of the disease only after a complete examination of the patient, taking into account various factors.

Biliary cirrhosis is usually divided into two forms - primary and secondary, each of which has its own characteristics. The development of the primary form is said to be when the disease develops under the influence of autoimmune factors and initially leads to the development of cholestasis and only then passes into cirrhosis of the liver.

Secondary biliary cirrhosis of the liver is a consequence of chronic inflammatory processes associated with a violation of the outflow of bile. But regardless of the form and causes of the disease, biliary cirrhosis has common signs and symptoms.

The primary form of the disease

Until now, despite many studies, it has not been possible to identify the exact causes of the development of the primary form of biliary cirrhosis. It is only known for certain that damage to liver cells occurs under the influence of T-lymphocytes, whose functions are aimed at suppressing the vital activity of foreign particles in the body. But for some reason, T-lymphocytes begin to consider the cells of the body as dangerous and begin to destroy them.

T-lymphocytes initially begin to affect the small bile ducts, leading to their destruction and the development of cholestasis. Due to the retention of bile, liver cells begin to suffer from toxic damage, as a result of which an inflammatory process begins in the liver. Affected hepatocytes are replaced by fibrous tissue, which forms scars in the organ. It has been noted that the more liver fibrosis progresses, the less pronounced the inflammatory process becomes.

stages

It is customary to distinguish 4 stages of development of primary biliary pathology:

1. First, there is inflammation of the interlobular and septal canals, which is accompanied by vasodilation. There is lymphocytic infiltration with granuloma formation.
2. The second - the inflammatory process passes to the liver parenchyma, going beyond the boundaries of the portal tracts. There is a lesion of most of the ducts, and the remaining intact bile ducts have an abnormal structure.
3. Third, progressive inflammation leads to more pronounced cholestasis, and adhesions from connective tissue form in the parenchyma.
4. Fourth - characterized by the absence of ducts in the portal passages, the process of necrosis of liver cells begins.

The reasons that lead to a malfunction of the immune system are unknown. But many scientists are inclined to believe that there is a conflict between lymphocytes and histocompatibility antigens, characteristic of the graft versus host reaction, since the mechanism for the development of cirrhosis is very similar to the processes occurring during such a reaction, but this version is still under consideration.

Like any autoimmune disease, biliary cirrhosis in 90% of cases affects women after 30-40 years. That is why there are versions that the causes are hormonal changes in the body, as well as the physiological deterioration of the body. Biliary cirrhosis of the primary form has the ability to spread within the same family, which confirms the hereditary predisposition to the disease.

Symptoms

Along with biliary liver damage, the concomitant development of other diseases of autoimmune origin is characteristic:

1. Systemic lupus erythematosus.
2. Scleroderma.
3. Rheumatoid arthritis.
4. Vasculitis.
5. Glomerulonephritis.
6. Sjögren's syndrome.
7. Autoimmune thyroiditis.

At the very beginning of the development of the disease, symptoms appear only in a small number of patients. In most patients, clinical signs occur only with extensive growth of fibrous tissue.

The very first and characteristic sign is considered itchy skin, which occurs due to a large amount of bile acids, which irritate the nerve endings. Sometimes itching is initially accompanied by jaundice, but it can also occur in later stages. Experts say that the later yellowness of the skin appears, the more favorable the prognosis of the disease.

Vascular asterisks and "hepatic palms" are extremely rare in this form of the disease. In half of the patients, hyperpigmented spots appear in the joints of the joints, and after that - in other parts of the body. In later stages, the pigmented areas of the skin thicken, and the external clinical picture resembles focal scleroderma.

Biliary cirrhosis is characterized by the appearance of xanthelasma in the eyelids, chest, elbows and knee joints.

Other symptoms:

1. Enlargement of the liver and spleen in size occurs in approximately 60% of patients.
2. Dyspeptic disorders, bitterness in the mouth, pain in the right hypochondrium.
3. General weakness, lack of appetite.
4. Dry skin.
5. Muscle and joint pain.
6. Subfebrile fever.

With the progression of cirrhosis, itching becomes constant and unbearable. Puffiness appears, ascites develops, and due to the expansion of the veins in the esophagus, internal bleeding may occur.

Diagnosis and treatment

Diagnosis of biliary cirrhosis is based on the data of a biochemical blood test, the detection of antimitochondrial antibodies and instrumental methods - ultrasound, CT and MRI of the liver. In primary biliary cirrhosis, the activity of liver enzymes increases, the ESR and the concentration of bile acids increase. Nearly every patient has antimitochondrial antibodies, and about half develop rheumatoid factor and antinuclear bodies.

Primary biliary cirrhosis is dangerous because there are no special drugs for its treatment, so all therapeutic measures are aimed at relieving symptoms. First of all, patients are prescribed a strict diet:

1. No more than 40 g of fat per day.
2. Protein intake 80-120 g per day.
3. Refusal of food containing preservatives and dyes.
4. Exclusion of alcoholic and carbonated drinks, strong tea and coffee.
5. Doctors recommend a lifelong diet number 5 and drinking regime - 1.5-2 liters of pure water per day.

What drugs are prescribed:

1. Cytostatics (Geksalen).
2. Corticosteroids (Prednisone).
3. Bisphosphonates (Alendronate).
4. Hepatoprotectors (Essentiale, Phosphogliv, Gepabene).
5. Cholagogue (Allohol).

Agents that suppress collagen synthesis can be selected - Kuprenil, D-penicillamine. Ursosan, Rifampicin and Phenobarbital are suitable for relieving itching. The only method by which the disease can be cured is a donor organ transplant.

Secondary cirrhosis

Secondary biliary cirrhosis, unlike primary, is more studied and understood. It develops when there is chronic stagnation of bile in the pathways located inside and outside the liver. What leads to secondary biliary cirrhosis:

1. Congenital abnormalities in the development of the biliary tract.
2. Cholecystolithiasis.
3. cholestasis.
4. Cysts and other benign neoplasms.
5. Cancer tumors in the pancreas.
6. Squeezing of the bile ducts by enlarged lymph nodes (lympholeukemia, lymphogranulomatosis).
7. Purulent or primary cholangitis.
8. Narrowing of the bile ducts after surgery.
9. Cholelithiasis.

These pathologies lead to prolonged stagnation of bile and an increase in pressure in the bile ducts, which causes them to swell. The chronic course of the disease provokes depletion of the walls of the ducts, and bile penetrates into the liver parenchyma. Under the influence of an acidic and aggressive liquid, the liver cells become inflamed, and the process of necrosis begins.

Affected hepatocytes are gradually replaced by fibrous tissue. The speed of this process is different - on average from 6 months to 5 years. The process is accelerated if a bacterial infection joins or complications develop. The disease leads to persistent liver failure, against which the last stage develops - hepatic coma.

Manifestations

Symptoms of primary and secondary biliary cirrhosis have much in common. But secondary liver damage occurs with equal frequency in both sexes, while the primary form is more characteristic of the female.

Clinical signs of disease progression:

At the last stages, signs join:

• portal hypertension;
• ascites;
• varicose veins of the esophagus and intestines.

Diagnosis and therapy

Diagnosis of secondary biliary cirrhosis consists in collecting anamnesis, patient complaints and examination. After that, the following examinations are prescribed:

1. Blood and urine tests.
2. Ultrasound of the liver.
3. MRI and CT.

The disease is characterized by an increase in:

• blood sugar;
• alkaline phosphatase;
• cholesterol;
• bilirubin; ALT.

Most patients are diagnosed with eosinophilia, anemia, and elevated ESR. Be sure to evaluate the amount of copper in the urine - a high content indicates the severity of the process. In a mandatory manner, diagnostics are carried out to identify gallstone disease, cholecystitis, cholangitis, and pancreatic lesions. But the most accurate diagnosis is made by taking a biopsy and histological examination of the material.

It is possible to delay the progression of the disease if the causes that cause stagnation of bile are excluded. Therefore, very often they resort to surgical intervention to remove stones or stent the duct. Liver transplantation does not always give a positive result, in ¼ of patients there is a recurrence of the disease.

If the operation is impossible, patients are prescribed hepatoprotectors, vitamins, antioxidants, antihistamines and antibiotics to prevent the development of a bacterial infection.

The development of the disease in children

Cirrhosis in childhood is not uncommon, but the biliary form practically does not occur in childhood. Primary biliary cirrhosis usually develops in middle-aged patients, but the secondary form of the disease can occur due to abnormal development of the biliary tract in children.

Treatment of biliary cirrhosis in childhood requires the intervention of experienced professionals and constant maintenance of the diet. With an unfavorable development of the disease, a liver transplant operation is performed.

Predictions and Complications

Primary biliary cirrhosis is primarily dangerous because it is impossible to establish the cause of the disease, so there are no specific methods of treatment. Doctors recommend eliminating all factors that can affect autoimmune processes:

1. Eliminate physical and nervous strain.
2. Avoid stressful situations.
3. Treat foci of infection.
4. Normalize the hormonal background.

Primary and secondary biliary cirrhosis have common complications:

Primary biliary cirrhosis is often complicated by concomitant autoimmune diseases: systemic lupus, scleroderma, rheumatoid arthritis, and others.

The skin very often suffers from the primary form, in addition to jaundice and hyperpigmentation, vitiligo is often observed - the appearance of white, non-pigmented areas of the skin.

Life expectancy depends on many factors, but based on statistics, you can determine the general indicators:

1. The primary form with a bilirubin level of up to 100 µmol/l - about 4 years of life, over 102 µmol/l - no more than 2 years.
2. Identified in the early stages and uncomplicated primary cirrhosis - about 20 years.
3. Secondary biliary cirrhosis with pronounced symptoms - 7-8 years.
4. The asymptomatic course of secondary cirrhosis increases life expectancy to 15-20 years.
5. Severe course of cirrhosis with complications - no more than 3 years.

Averages indicate that primary and secondary forms of cirrhosis end in death within 8 years after the onset of the first symptoms. But it is extremely difficult to make accurate predictions of life expectancy, especially with the development of an autoimmune disease.

Biliary cirrhosis is not only the rarest, but also the most dangerous of all types of disease. It is especially difficult to predict the development of primary cirrhosis, as well as to choose a treatment or take preventive measures. It is important for patients with biliary liver damage not to give up, and to follow the advice and prescriptions of the attending physician - with the right approach, life expectancy can be extended by several decades.

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Ascitic fluid infection

(CP) often causes secondary immunodeficiency. Spontaneous bacterial peritonitis(SBP) is perhaps the most characteristic infectious complication of liver cirrhosis: according to the literature, it is detected in 7-31% of patients with ascites.

Clinical picture of SBP

Clinical symptoms of SBP include diffuse abdominal pain of varying intensity, without a clear localization; fever and an increase in hepatic encephalopathy without visible provoking factors. In 8-10% of patients, a positive symptom of peritoneal irritation is determined. Abdominal stiffness is rare in tense ascites. Fever in SBP is observed in 50% of patients and may be associated with septic shock, often the body temperature rises only to subfebrile numbers. In 10-15% of patients, vomiting, diarrhea, signs of intestinal paresis occur. In a number of patients, the disease manifests with signs of septic shock with severe hypotension, tachycardia, and oliguria.
However, in 10–33% of patients, there are no initial symptoms and the disease is detected incidentally during the study. ascitic fluid(AZh). This may be due to the fact that usually in such patients the clinic of hepatic encephalopathy predominates, which obscures other symptoms.
Most episodes of AF infection are caused by intestinal bacteria. In 70% of cases, bacterial ascites is caused by Gram-negative bacteria. Escherichia coli and Klebsiella spp..; 10–20% are Gram-positive cocci ( Streptococcus pneumoniae), often meets candida albicans. Anaerobic flora is sown in 3–4% of cases.
The main factors predisposing to infection of ascitic fluid include the following (according to Arroyo V.):
- severe liver disease (serum bilirubin level above 3.2 mg / dl, blood platelets below 98 thousand / ml);
- gastrointestinal bleeding;
- the content of AF protein is less than 1 g / dl and / or the C3 component of complement is below 13 mg / dl;
– urinary tract infection;
– excessive bacterial growth;
- medical manipulations: urinary, intravenous catheter and / or the patient's stay in the intensive care unit;
- history of SBP episodes.

Diagnosis of infection of ascitic fluid

Due to the fact that the clinical manifestations of the complication under consideration are often nonspecific, the diagnosis is based on the study of AF. The diagnostic criteria are presented in Table. ten .

Indications for emergency diagnostic paracentesis in cirrhosis are symptoms of infection of ascitic fluid (abdominal pain, fever, leukocytosis, the appearance or increase in the depth of encephalopathy or the severity of renal failure); gastrointestinal bleeding or hypotension.
SBP itself is characterized by a positive result of AF culture, the content of neutrophils in it is more than 250 in 1 mm 3 and the absence of an intra-abdominal source of infection.
With monomicrobial non-neutrophilic bacterial ascites, the AF culture is positive, and the content of neutrophils is less than 250 in 1 mm 3. In culture-negative neutrophilic ascites, AF culture is not accompanied by bacterial growth, but the number of neutrophils exceeds 250 per 1 mm 3 in the absence of an intra-abdominal source of infection.
Secondary bacterial peritonitis may be suspected when a polymicrobial culture is obtained in the studied AF in combination with more than 250 neutrophils per 1 mm 3 . This variant of infection occurs in case of intestinal perforation. These patients require urgent surgical intervention.
Polymicrobial bacterial ascites is an iatrogenic condition caused by intestinal injury during paracentesis. Culture is positive, but polymicrobial bacterial ascites usually does not cause an increase in neutrophils and resolves on its own.
Spontaneous bacterial pleural empyema occurs in patients with hydrothorax in the absence of pneumonia (development and treatment are the same as in SBP).

Antibacterial therapy is indicated for patients with SBP proper, culture-negative neutrophilic ascites, and monomicrobial non-neutrophilic bacterial ascites with clinical signs of infection. The drug of choice is an antibiotic from the group of cephalosporins of the 3rd generation cefotaxime: 2 g is used every 8 hours for 5-7 days (effective in 90% of cases). Of the other drugs in this group, ceftriaxone and cefonicide are prescribed. As an alternative method of treatment, a combination of 1 g of amoxicillin and 0.2 g of clavulanic acid every 6 hours is used, this therapy is effective in 85% of patients. Oral administration of ofloxacin 400 mg twice daily in uncomplicated SBP is as effective as intravenous cefotaxime. Patients treated prophylactically with quinolones are given cefotaxime.

Evaluation of the effectiveness of treatment

The European Society for the Study of Ascites recommends repeating the AF study after 2 days. The effectiveness of antibiotic therapy is determined by the disappearance of clinical symptoms and a decrease in the number of neutrophils in the AF by more than 25%. Replace the antibiotic should be based on the sensitivity of the isolated microorganism. In case of treatment failure, it is also necessary to remember the possibility of developing secondary peritonitis. The life expectancy of patients after an episode of SBP is 1 year in 30–50% of cases and 2 years in 25–30%.
The most important negative predictor of survival is the development of renal failure prior to the episode of SBP. The appointment of albumin at a dose of 1.5 g per 1 kg of body weight on the day of diagnosis and 1 g/1 kg for the next 3 days can reduce the number of deaths from 30 to 10%. Other factors associated with increased mortality include: advanced age, positive ascites culture, and high bilirubin levels.

Prevention

Since recurrent episodes of SBP occur in 70% of patients and are the leading cause of death, these patients should be included in the liver transplantation waiting list. Such patients are shown to carry out the prevention of infection of AF with drugs of the fluoroquinolone group (norfloxacin, ciprofloxacin) constantly, until the disappearance of ascites or liver transplantation. For prophylactic purposes, antibacterial agents are also prescribed in case of bleeding from the upper gastrointestinal tract, regardless of the presence or absence of ascites. Norfloxacin 400 mg twice daily is the drug of choice. per os or via nasogastric tube for at least 7 days. Before starting a prophylactic course, it is necessary to exclude the presence of SBP or other infection.

Hepatorenal syndrome

Hepatorenal syndrome(HRS) - functional renal failure occurring without organic changes in the kidneys. The International Society for the Study of Ascites recommends using the following criteria for the diagnosis of HRS (Salerno F., Gerbes A., Gines P., Wong F., Arroyo V.):
- cirrhosis of the liver with ascites;
- Serum creatinine above 1.5 mg/dl (more than 133 mmol/l);
- there is no decrease in serum creatinine below 1.5 mg / dl (133 mmol / l) after 2 days of discontinuation of diuretic therapy and the introduction of fluid with albumin (the recommended dose of albumin is 1 g per 1 kg of body weight per day up to a maximum dosage of 100 g / days);
- there are no other reasons for the development of renal failure (shock, sepsis, a decrease in the volume of circulating plasma, the use of nephrotoxic drugs);
- Excluded parenchymal kidney disease in the presence of proteinuria more than 500 mg / day, microhematuria (more than 50 erythrocytes per field of view) and / or changes in the kidneys during ultrasonography.
In patients with decompensated cirrhosis, functional renal failure eventually joins and progresses. Approximately 15% of patients with HRS develop within 6 months from the moment of the first hospitalization for ascites, in 40% - within 5 years.

Classification

Perhaps the development of two types of hepatorenal syndrome. Type 1 HRS is rapidly decompensated, with serum creatinine usually above 2.5 mg/dL. This syndrome is more likely to occur in the setting of SBP, alcoholic hepatitis, or volumetric paracentesis without subsequent albumin replacement. Without treatment or liver transplantation, patients with HRS type 1 live no more than 2 weeks.
HRS type 2 develops in patients with decompensated liver disease and is closely associated with resistant ascites. It is characterized by a slow course, less severity of renal failure (serum creatinine does not exceed 1.5-2.5 mg / dl).

Clinical signs and symptoms

There are no specific clinical symptoms of HRS. Clinical signs are defined by a combination of acute renal failure with progressive liver failure and portal hypertension. Thirst, apathy, weakness are characteristic. In patients, the abdomen increases in volume, falls arterial pressure(BP), possibly an increase in jaundice. Typical renal signs include oliguria, a decrease in the filtration function of the kidneys with a moderate increase in serum creatinine and blood urea nitrogen. At the same time, the concentration ability of the kidneys is quite preserved. Proteinuria, changes in urinary sediment are minimal and rarely detected. In the terminal stage, hyperkalemia, hypochloremia may join.

Diagnostics

If a patient has severe ascites without a response to ongoing therapy, arterial hypotension, hyponatremia, one should be aware of the likelihood of developing HRS. Diagnosis is based on IAC criteria (International Ascites Club, 1996). All criteria must be met to make a diagnosis. Once renal failure has been identified, the diagnosis of HRS is made by exclusion. Prerenal renal failure due to fluid loss, hemodynamic and septic shock leading to acute tubular necrosis, nephrotoxic drugs, chronic kidney disease, and urinary tract obstruction should be consistently ruled out. HRS is diagnosed when all other causes of renal failure have been ruled out and both hypovolemia and sepsis have been treated. At the same time, it is possible to combine HRS with another pathology of the kidneys, which does not currently determine the severity of the patient's condition.

Differential Diagnosis

Most often, HRS has to be differentiated from acute tubular necrosis in toxic nephropathies, nephritis, severe infection (sepsis, acute cholangitis, leptospirosis, fever), anuria in decompensated heart failure.

In acute tubular necrosis, kidney damage is possible due to the nephrotoxic effect of the substance that led to acute liver failure- OPN (acetaminophen, pale grebe), or due to the action of antibiotics, radiopaque drugs. Renal failure in patients with cirrhosis may be caused not by HRS (Table 11), but by previous kidney diseases (glomerulonephritis, pyelonephritis, etc.). Without previous liver pathology, acute renal failure in most cases occurs with acute viral hepatitis. Viral hepatitis causes the development of glomerulonephritis, IgA nephropathy, cryoglobulinemia. Primary sclerosing cholangitis is associated with membranous and membranous proliferative glomerulonephritis, vasculitis with antineutrophil antibodies, and tubulointerstitial nephritis.
Some diseases occur with simultaneous damage to the liver and kidneys: sarcoidosis, amyloidosis, systemic lupus erythematosus, Sjögren's syndrome, non-alcoholic steatohepatitis in diabetes mellitus with diabetic nephropathy, polycystic liver disease, shock, sepsis and circulatory failure. Kidney damage (interstitial nephritis) is possible in patients with liver disease after taking certain drugs, in particular aminoglycosides. Concomitant use of angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers) and non-steroidal anti-inflammatory funds(NSAIDs) causes a drop in blood pressure, a decrease in glomerular filtration and the development of prerenal hemodynamic renal failure.

Treatment of HRS is carried out against the background of ongoing therapy for liver failure. If necessary, paracentesis is performed, followed by the introduction of albumin, but liver transplantation is undoubtedly the best method of treatment. Of the pharmacological agents, systemic vasoconstrictors and plasma substitutes are considered the drugs of choice (Fig. 6).
Vasoconstrictors prescribed due to the fact that the initial link in the pathogenesis of HRS is the expansion of the arteries of the internal organs, caused by the activation of endogenous vasoconstrictor systems with partial spasm of the renal vessels. Intravenous administration of terlipressin alone or in combination with albumin as a plasma substitute significantly improves renal function and reduces serum creatinine below 1.5 mg/dL in 60–75% of patients treated for 5 days. There were no recurrences of HRS in these studies.
Albumen used on the first day at a dose of 1 g per 1 kg of body weight, on subsequent days at 20–40 g, terlipressin 0.5 mg intravenously every 4 hours, the maximum dose is 2 mg every 4 hours. Terlipressin is not registered in a number of countries, for example, in the USA and Russia, it is therefore possible to use midodrine (alpha-adrenergic agonist) in conjunction with octreotide (an analogue of somatostatin and a glucagon inhibitor) and albumin. Albumin is administered at the same dose - orally 2 times a day, midodrine - at a dose of 2.5–7.5 mg (maximum 12.5 mg), octreotide - subcutaneously 2 times a day at a dose of 100 mg (maximum 200 mg). Also, together with albumin, norepinephrine, another alpha-adrenergic agonist, can be used at a dose of 0.5-3 mg / h intravenously through an infusator or dopamine - 100 mg in 12 hours (in the absence of an increase in diuresis during the specified time, it is necessary to stop the administration of dopamine).
The duration of therapy is 1-2 weeks, the goal is to reduce the level of serum creatinine below 1.5 mg / dl. It should not be forgotten that when using vasoconstrictors, spastic abdominal pain, nausea, vomiting, and headache may appear. The reason is an increase in the tone of the smooth muscles of the vascular wall, which leads to narrowing of the veins and venules, especially in the abdominal cavity. During treatment, it is necessary to control hemodynamic parameters (pulse, blood pressure). Some studies have shown that patients who respond to therapy (when serum creatinine levels fall to 1.5 mg/dL) have a higher survival rate than non-responders.
Thus, the main goal of medical treatment of HRS is the normalization of kidney function, followed by liver transplantation. Patients successfully treated with vasopressin analogues and albumin before liver transplantation have the same post-transplant outcomes and survival rates as transplant patients without HRS. This supports the concept that HRS should be treated very aggressively before liver transplantation, as this improves kidney function and leads to better outcomes. May improve kidney function transjugular portosystemic shunt(TIPS).
An important role is given to preventive measures. There are two clinical situations where the development of HRS can be prevented, in particular in spontaneous bacterial peritonitis and alcoholic hepatitis. In SBP, albumin is prescribed at a dose of 1.5 g per 1 kg of body weight intravenously on the day of diagnosis, after 48 hours another 1 g is administered. The incidence of HRS in such patients decreases from 30 to 10%, and survival improves accordingly. The administration of pentoxifylline 400 mg 2-3 times a day orally for a month to patients with alcoholic hepatitis reduces the incidence of HRS and mortality from 35% and 46% to 8% and 24%, respectively.

Portal hypertension, bleeding from varicose veins of the esophagus and stomach

Bleeding out varicose veins(VRV) of the esophagus and stomach is a critical condition in which more than 20% of patients die within the next 6 weeks. In 30% of patients with viral cirrhosis of the liver, esophageal EVs form in
within 5 years, with alcoholic cirrhosis - in 50% of cases in 2 years.
Varicose veins of the esophagus and stomach with bleeding from them - a clinical manifestation portal hypertension(PG). Currently, the following definition is accepted: PH is a clinical symptom complex, which is hemodynamically manifested by a pathological increase in the portal pressure gradient, which is accompanied by the formation of portosystemic collaterals, through which blood is discharged from the portal vein around the liver. The portal pressure gradient is the difference between the pressure at the portal and lower hollow ve not (NVC), normally it is 1-5 mm Hg. Art. Clinically significant portal hypertension becomes with an increase in the portal pressure gradient of more than 10 mm Hg. Art. Below and in Fig. 7 shows the classification of GHG based on the localization of the portal block.

Classification of portal hypertension

1. suprahepatic

Hepatic vein thrombosis (Budd-Chiari syndrome, tumor invasion)
Obstruction of the inferior vena cava (membrane in the lumen of the IVC, tumor invasion)
Diseases of the cardiovascular system (constrictive pericarditis, severe tricuspid regurgitation)

2. Intrahepatic

Presinusoidal

Rendu-Osler disease
Congenital fibrosis of the liver
Thrombosis of the branches of the portal vein (severe bacterial cholangitis, malignant neoplasms)
Primary biliary cholangitis, primary sclerosing cholangitis
Granulomatosis (schistosomiasis, sarcoidosis, tuberculosis)
Chronic viral hepatitis

Myeloproliferative diseases
Nodular regenerative hyperplasia
Idiopathic (non-cirrhotic) portal hypertension
Wilson's disease
Hemochromatosis
· Polycystic
Amyloidosis
Exposure to toxic substances (copper, arsenic, 6-mercaptopurine)

sinusoidal I

All CPU cases
Acute alcoholic hepatitis
Severe viral hepatitis
Acute fatty liver of pregnancy
Vitamin A toxicity
Systemic mastocytosis
hepatic purpura
Cytotoxic drugs

Postsinusoidal

venous occlusive disease
Alcoholic centrilobular hyaline sclerosis

3. Subhepatic

Portal vein thrombosis
Cavernous transformation of the portal vein
Thrombosis of the splenic vein
Visceral arteriovenous fistula
Idiopathic tropical splenomegaly

Clinical manifestations of portal hypertension

When examining a patient, it is possible to identify dilated veins of the anterior abdominal wall, diverging from the navel (jellyfish head). However, one or more saphenous veins in the epigastric region are more commonly seen. Sometimes in the umbilical region, vascular venous murmurs can be heard. Enlargement of the spleen is one of the most important diagnostic signs of PH. A dense liver indicates cirrhosis, a soft one indicates an extrahepatic portal block. The presence of ascites in cirrhosis implies the development of liver failure. Anorectal varicose veins must be differentiated from hemorrhoids that are not related to PH.

Diagnostics

In a patient with liver disease, the following clinical signs indicate the development of PH: splenomegaly, ascites, hepatic encephalopathy, and esophageal varices. Conversely, if any of these symptoms are detected, it is necessary to exclude PG and cirrhosis.
Indirect confirmation of the diagnosis of PH is the detection of VRV of the esophagus in esophagogastroduodenoscopy(EGDS). In the absence of VRV, EGDS is required at least once every 2 years, if available, annually. In addition, when performing endoscopy, the risk of bleeding from the esophagus of the esophagus and / or stomach and, accordingly, the need for preventive treatment are necessarily assessed.

Classification of varicose veins of the esophagus according to their size

Grade I - solitary veins that decrease when pressure is applied to them with an endoscope
Grade II - several columns of veins that do not merge around the circumference of the esophagus, but do not decrease when pressure is applied to them with an endoscope
Grade III - the veins merge around the entire circumference of the esophagus
In case of intolerance to endoscopy, it is possible to use a video capsule, but this method still needs to be improved in diagnosing the severity of PG.
When conducting ultrasound, the signs of PG are the expansion of the portal vein up to 13 mm or more, a decrease in blood flow velocity in it or retrograde blood flow, the appearance of porto-caval collaterals (paraumbilical vein, varicose veins of the splenic vein, etc.). In order to diagnose PH, such studies as computed tomography of the abdominal organs, radionuclide liver scan are less frequently performed. Venography (splenic or transhepatic portography), if necessary, allows you to identify the level and presumably the cause of impaired portal blood flow. The pressure in the portal vein can be assessed using a balloon catheter, which is passed through the femoral or jugular vein into the small hepatic vein until it stops. When necessary, the pressure in the portal vein is determined directly - by its percutaneous transhepatic catheterization or indirectly - by transjugular catheterization of one of the hepatic veins, which measures the pressure in the hepatic vein and the pressure of the hepatic vein wedging. The latter increases with sinusoidal (including cirrhosis) and postsinusoidal PG, but does not change with presinusoidal PG.
The "gold standard" in the assessment of GHG and its severity is the portal pressure gradient.
If additional information is needed (for example, in preparation for a porto-caval anastomosis) or if percutaneous transhepatic portal venous catheterization is not possible for some reason, the patency of the portal vein and the direction of blood flow in it can be assessed using indirect portography, in which a contrast agent is injected into the celiac trunk , splenic or superior mesenteric artery.

Differential Diagnosis

The source of bleeding in PH can be VRV of the esophagus, stomach and portal hypertensive gastropathy. In addition, varicose bleeding must be differentiated from bleeding from erosive and ulcerative lesions of the stomach and duodenum(DPK). Among the rare causes of bleeding from the upper gastrointestinal tract, angiodysplasia of the vessels of the stomach and intestines (Weber-Osler-Randu disease), rupture of an aortic aneurysm (usually into the lumen of the duodenum), tuberculosis and syphilis of the stomach, hypertrophic polyadenomatous gastritis (Menetrier's disease), foreign bodies
stomach, pancreatic tumors, damage to the bile ducts or rupture of the vascular formations of the liver, blood clotting disorders.

Treatment of acute varicose bleeding

The algorithm for the treatment of acute variceal bleeding is shown in Fig. eight . In accordance with the portal pressure reduction mechanism, all drugs with drug therapy for portal hypertension can be divided into two main groups.
Group 1 - vasodilators that affect the dynamic component of portal resistance (nitrates - isosorbide 5-mononitrate). Nitrates are rarely used as monotherapy and are usually used in combination with vasopressin.
Group 2 - vasoconstrictors that reduce portal pressure, cause splanchnic vasoconstriction and, accordingly, reduce portal blood volume. Direct vasoconstrictors include vasopressin and its synthetic analogue, terlipressin. These drugs directly affect vascular smooth muscle cells. The mechanism of action of indirect vasoconstrictors is associated with inhibition of the activity of endogenous vasodilators (in particular, glucagon). This group includes somatostatin and its synthetic analogue octreotide.
Vasopressin is first administered intravenously (within 20 minutes) at a dose of 20 IU per 100 ml of 5% glucose solution, after which they switch to a slow infusion of the drug, administering it over 4-24 hours at a rate of 20 IU per 1 hour until bleeding stops completely. The combination of vasopressin with glyceryl trinitrate can reduce the severity of systemic side effects of vasopressin. Terlipressin is used initially as a bolus injection at a dose of 2 mg, and then intravenously at 1 mg every 6 hours. Octreotide is administered as a bolus at a dose of 25–50 mcg, followed by a continuous infusion of 25–50 mcg/h.
With a small amount of bleeding from varicose veins of the esophagus and stable hemodynamic parameters, it is advisable to carry out endoscopic sclerotherapy. Paravasal or intravasal administration of sclerosants (polidocanol or ethoxysclerol) helps stop bleeding in more than 70% of patients.
In case of massive bleeding, when sclerosing therapy is impossible due to poor visibility, they resort to balloon tamponade esophageal varicose veins using the Sengstaken-Blakemore probe or (with localization of varicose veins in the fundus of the stomach) the Linton-Nachlass probe. The probe is installed for a period of no more than 12–24 hours. In some patients, after its removal, bleeding may resume.
The inability to stop bleeding from varicose veins of the esophagus, its rapid recurrence after initial hemostasis, as well as the need to use large doses of preserved blood (more than 6 doses within 24 hours) are indications for surgical treatment(bypass surgery, transsection of the esophagus).
The recommendations for the treatment of acute variceal bleeding can be summarized as follows.
1. It is best to use a combination of vasoactive drugs (as early as possible, preferably during transport to the clinic) and endoscopic procedures.
2. It is possible to use terlipressin, somatostatin, octreotide, vasopressin in combination with nitroglycerin. Drug treatment can last up to 2-5 days.
3. Endoscopic doping of the VRV of the esophagus or sclerotherapy is the tactic of choice for acute bleeding in this area. When bleeding from the gastric RV, it is better to use endoscopic obturation with tissue adhesive.
4. Endoscopic examination (and treatment) must be performed within 12 hours from the onset of bleeding.
5. All patients require prophylactic broad-spectrum antibiotics.
6. If endoscopic and medicinal methods of therapy are ineffective, the imposition of TIPS is recommended.

Prevention

Primary prevention variceal bleeding is performed in patients with cirrhosis of classes A and B according to Child-Pugh with minor varicose veins and / or with portal hypertensive gastropathy. For this, non-selective beta-blockers (propranolol, nadolol, timolol) are used, which can reduce the risk of first bleeding by approximately 30-40%. The drugs are prescribed at a dose that reduces the resting heart rate by 25%, or, with an initially low pulse, up to 55 beats per minute. Doses of propranolol range from 80 mg/day orally (initial dose) to 320 mg/day (maximum dose). In case of contraindications, the use of isosorbide 5-mononitrate is an alternative. Upon reaching the target dosages of beta-blockers, the portal pressure gradient decreases to less than 10 mm Hg. Art., which reduces the risk of bleeding.
Endoscopic ligation of the VRV of the esophagus is indicated to prevent bleeding in patients with moderate to large esophageal varices.
Secondary prevention should begin as early as possible, since the first episode of gastrointestinal bleeding in patients with cirrhosis in 60% of cases is accompanied by its relapse. Patients without primary prophylaxis are given beta-blockers or endoscopic ligation, or a combination of both. Patients treated with beta-blockers undergo endoscopic VRV ligation from the 6th day from the moment of the first bleeding.

Dilutional hyponatremia

Dilutional hyponatremia, or dilutional hyponatremia, in patients with cirrhosis is a clinical syndrome and is diagnosed based on the following features:
– decrease in serum sodium level ≤130 mmol/l;
– increase in extracellular fluid volume;
- the presence of ascites and / or peripheral edema.
Dilutional hyponatremia occurs in an average of one third (30–35%) of hospital patients with cirrhosis and ascites. It should be distinguished from true hyponatremia, which develops with a decrease in circulating plasma volume due to an overdose of diuretic drugs in patients without ascites and edema.
Predisposing factors for the development of dilutional hyponatremia are considered to be taking NSAIDs and performing volumetric paracentesis without the subsequent administration of plasma-substituting solutions.

Clinical manifestations

In patients with cirrhosis, dilutional hyponatremia usually develops within a few days to weeks, although acute conditions are also possible. In most patients, the serum sodium level ranges from 125 to 130 mmol/l, but in some it can decrease to 110–125 mmol/l. Clinically, hyponatremia is manifested by nausea, vomiting, apathy, anorexia, lethargy, convulsions, disorientation, and headache. The neurological symptoms associated with this condition can be difficult to distinguish from manifestations of hepatic encephalopathy.

The first step in the treatment of dilutional hyponatremia is the restriction of fluid management and the abolition of diuretic drugs (Na content below 125 mmol / l). Limiting the amount of liquid to 1 liter per day prevents a further drop in sodium levels, but does not lead to its increase. In addition to limiting fluid intake, patients should follow a salt-free diet. Under these conditions, the appointment of hypertonic saline solutions is impractical due to their low efficiency, an additional increase in the volume of extracellular fluid and the possible aggravation of edema and ascites.
In some cases, determined individually depending on the patient's condition, correction of hyponatremia is necessary.
The dose of isotonic sodium solution is calculated as follows: the required amount of Na, mmol \u003d (the desired level of Na - the real level of Na) x body weight, kg x 0.6, where 0.6 is the coefficient.
Since 1 liter of 0.9% NaCl solution contains 390 mmol Na, the patient must inject the amount of 0.9% NaCl solution in combination with colloids (albumin) = the required amount of Na / 390 mmol Na.
Differential diagnosis of hyponatremia is carried out with hypoosmolal hyponatremia.

■ Primary sodium loss

1. Outdoor loss
2. Losses through the gastrointestinal tract
3. Kidney loss

■ Primary hyperhydremia

1. Hypersecretion of ADH (antidiuretic hormone)
2. Insufficiency of the adrenal cortex
3. Hypothyroidism
4. Chronic renal failure

Currently, phase III multicenter clinical trials are underway on the use of specific V2 receptor antagonists of antidiuretic hormone (satavaptan, tolpavaptan).

Conclusion

In the last 15–20 years, many clinical and experimental studies have been devoted to the study of liver cirrhosis and its complications. Progress has been made in studying the etiological and predisposing factors for this disease, new methods of treatment are being applied. At the same time, many issues of the pathogenesis of cirrhosis complications remain insufficiently studied, and the results of scientific research conducted in this direction are contradictory. The only effective way of radical help for this category of patients is liver transplantation, which, unfortunately, is not always possible to perform in a timely manner. Properly selected tactics for the treatment of complications of liver cirrhosis is a very difficult task, but its implementation will allow patients to safely wait for organ transplantation.

Annex 2

Low Sodium Diet

If you have been advised a sodium-restricted diet, salting is avoided and the total amount of sodium should not exceed 1.5–2 g per day. Sodium restriction leads to a reduction in the dose of diuretics, faster resolution of ascites and a reduction in hospital stay.

How to Follow a Sodium Restricted Diet

Do not add salt to food (the salt shaker should not be on the table !!!)
Keep a food diary in which you count the amount of sodium you get from food
Do not use canned, ready-frozen, dried foods, factory sauces
Avoid fast foods
Avoid any products containing baking powder (baking powder) and baking soda (cakes, biscuits, cakes, pastries)
Use fresh or dry herbs (not prepackaged seasonings!!!), lemon juice, balsamic vinegar, pepper, onion and garlic to enhance the flavor of your food
Be patient – ​​It may take a few weeks for you to get used to the low-sodium diet

Be aware that some medications may contain high amounts of sodium, especially non-steroidal anti-inflammatory drugs. Antibiotics for intravenous administration contain on average 2.1–3.6 mmol sodium per gram, and the amount in infusion solutions is indicated on the vial.
If you are taking diuretics, record your daily body weight, daily urine output (difference between fluids you drink and excreted), abdominal volume (measured with a tape measure at the level of your navel), and sodium intake from food. Weight loss should not exceed 1000 g per day in patients with ascites and peripheral edema and 500 g per day in the presence of ascites alone. Proper adherence to the recommendations of the attending physician will allow you to prevent complications of diuretic therapy and reduce the time of hospitalization.

Approximate sodium content in the daily diet for a patient with liver cirrhosis

· Breakfast

Semolina porridge with cream and sugar or baked fruit ≈20 mg
1 egg ≈170 mg
50–60 g bread with unsalted butter and marmalade (jelly or honey) ≈220 mg
Tea or coffee with milk ≈10 mg

· Dinner

Vegetable salad ≈50–70 mg
Soup without salt ≈ 800–1000 mg
90 g white fish ≈ 150 mg
3 potatoes ≈ 20 mg
Fruit (fresh or baked) ≈15–30 mg

· Afternoon snack

50–60 g bread ≈ 220 mg
Unsalted butter, jam, or tomato ≈5–10 mg

· Dinner

Greens or lettuce ≈ 16–30 mg
Sour cream ≈ 40 mg
100 g beef, poultry meat ≈80 mg
Pasta ≈ 10 mg
Fruit (fresh or baked) or fruit juice gelatin jelly ≈ 15–30 mg
Tea or coffee with milk ≈ 10 mg

Total: 1900-2000 mg sodium per day.

RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2015

Alcoholic fatty liver [fatty liver] (K70.0), Alcoholic liver failure (K70.4), Alcoholic hepatitis (K70.1), Alcoholic liver fibrosis and sclerosis (K70.2), Alcoholic liver cirrhosis (K70.3) , Biliary cirrhosis, unspecified (K74.5), Venous occlusive disease of the liver (K76.5), Secondary biliary cirrhosis (K74.4), Hepatorenal syndrome (K76.7), Granulomatous hepatitis, not elsewhere classified (K75.3), Fatty liver, not elsewhere classified (K76.0), Liver infarction (K76.3), Nonspecific reactive hepatitis (K75.2), Acute and subacute liver failure (K72.0), Primary biliary cirrhosis (K74.3 ), Portal hypertension (K76.6), Sclerosis of the liver (K74.1), Toxic liver injury with hepatic necrosis (K71.1), Toxic liver injury with fibrosis and cirrhosis of the liver (K71.7), Toxic liver injury with cholestasis ( K71.0), Toxic liver damage, occurring as acute hepatitis (K71.2), Toxic chronic active hepatitis (K71.5), chronic lobular hepatitis (K71.4), chronic persistent hepatitis (K71.3), hepatic fibrosis ( K74.0), Chronic hepatitis, not elsewhere classified (K73), Chronic passive plethora of the liver (K76.1), Centrilobular hemorrhagic necrosis of the liver (K76.2)

Gastroenterology

general information

Short description

Recommended
Expert Council
RSE on REM "Republican Center
health development"
Ministry of Health
and social development
Republic of Kazakhstan
dated December 10, 2015
Protocol No. 19

Cirrhosis of the liver is a diffuse process characterized by fibrosis and transformation of the normal structure of the liver with the formation of regeneration nodes. Cirrhosis of the liverrepresents the final stage of a number of chronic liver diseases (WHO definition).

Protocol code:

ICD-10 code(s):
K70 Alcoholic liver disease
K70.0 Alcoholic fatty liver
K70.1 Alcoholic hepatitis
K70.2 Alcoholic fibrosis and sclerosis of the liver
K70.3 Alcoholic liver cirrhosis
K70.4 Alcoholic liver failure
K71 Liver toxicity
K71.0 Toxic liver injury with cholestasis
K71.1 Toxic liver injury with hepatic necrosis
K71.2 Toxic liver damage, proceeding as acute hepatitis
K71.3-71.5 Toxic damage to the liver, proceeding according to the type of chronic hepatitis
K71.7 Liver toxicity with fibrosis and cirrhosis
K72 Liver failure, not elsewhere classified
K72.0 Acute and subacute liver failure
K73 Chronic hepatitis, not elsewhere classified
K74 Fibrosis and cirrhosis of the liver
K74.0 Liver fibrosis
K74.1 Sclerosis of the liver
K74.3 Primary biliary cirrhosis
K74.4 Secondary biliary cirrhosis
K74.5 Biliary cirrhosis, unspecified
K75 Other inflammatory diseases of the liver
K75.2 Nonspecific reactive hepatitis
K75.3 Granulomatous hepatitis, not elsewhere classified
K76 Other liver diseases
K76.0 Fatty liver, not elsewhere classified
K76.1 Chronic passive plethora of liver
K76.2 Centrilobular hemorrhagic necrosis of the liver
K76.3 Liver infarction
K76.5 Veno-occlusive liver disease
K76.6 Portal hypertension
K76.9 Other specified liver diseases

Abbreviations used in the protocol:
AJ - ascitic fluid;
ALT - alanine aminotransferase;
anti-LKM 1 - antibodies to hepatic-renal microsomes
AST - aspartate aminotransferase
APTT - activated partial thromboplastin time,
VRVP - varicose veins of the esophagus;
GGTP - gamma-glutamyl transpeptidase;
GPS - hepatopulmonary syndrome;
GDS - hepatorenal syndrome;
HCC - hepatocellular carcinoma;
KNF - Kazakhstan national formulary;
CT - CT scan;
LS - medicines;
MBA - microwave ablation;
MRI - Magnetic resonance imaging;
NSAIDs - non-steroidal anti-inflammatory drugs;
UAC - general blood analysis;
OAM - general urine analysis;
OZhSS - total iron-binding capacity;
OPN - acute renal failure;
PMYAL - polymorphonuclear leukocytes;
PTI - prothrombin index;
PE; - hepatic encephalopathy;
RFA - radiofrequency ablation;
CH - heart failure;
T4 free - thyroxine free;
TP - Liver transplant;
TSH - thyroid-stimulating hormone;
UDHC - ursodeoxycholic acid;
ultrasound - ultrasound procedure;
FPN - fulminant hepatic encephalopathy;
CHF - chronic heart failure;
HEPA - chemoembolization of the hepatic artery;
CP - cirrhosis of the liver;
SHF - alkaline phosphatase;
ECG - electrocardiogram;
EGDS - esophagogastroduodenoscopy;
EchoCG - echocardiography;
AASLD- American Association for the Study of Liver Diseases;
EASL- European Association for the Study of the Liver;
IAC- international society for the study of ascites;
SAAG- serum albumin-ascites gradient (albumin gradient).

Protocol development date: year 2013.

Date of protocol revision: 2015

Protocol Users: gastroenterologists, hepatologists, infectious disease specialists, surgeons, transplant surgeons, oncologists, therapists, general practitioners

An assessment of the degree of evidence of the recommendations provided is presented in Table 1.
Table 1. Level of evidence scale:

Classification

Clinical classification cirrhosis of the liver is based on the indication:
etiological factor;
The class of gravity
The patient's mortality prognosis index -MELD;
complications.

Clinical classification of the causes of liver fibrosis and cirrhosis (“Schiff Liver Diseases”, Eugene R. et al., 2012) is shown in Table 2.

Table 2 Causes of liver fibrosis and cirrhosis

Clinical picture

Symptoms, course

Diagnostic Criteria for Making a Diagnosis:
Clinical and instrumental signs of intrahepatic portal hypertension, histological signs of cirrhosis.

Complaints and anamnesis:
Complaints:
drowsiness, weakness, increased fatigue (with severe drowsiness, as well as with irritability and aggressive behavior, it is necessary to exclude hepatic encephalopathy);
Skin itching, icterus of the sclera and mucous membranes, frenulum of the tongue, darkening of the urine (as a rule, indicates liver failure);
An increase in the volume of the abdomen due to the accumulated fluid (more than 10-15 liters can accumulate), with a large amount of it, a picture of “tense ascites” is created, bulging of the navel;
Expansion of the veins of the anterior abdominal wall in the form of a "head of a jellyfish";
Bleeding gums, nosebleeds, petechial hemorrhages, bruising at injection sites due to impaired synthesis of blood coagulation factors in the liver and thrombocytopenia with hypersplenism;
Vomiting with an admixture of blood, melena, rectal bleeding from varicose veins;
fever (with the addition of infections);
Difficulty in breathing with severe ascites (due to increased intra-abdominal pressure and limited mobility of the diaphragm, hydrothorax);
decreased libido, amenorrhea.

Anamnesis: the features of the anamnesis of the disease depend on the etiology and chronology of the progression of cirrhosis.

Physical examination allows you to identify:
telangiectasia on the upper half of the trunk and face;
palmar erythema;
· jaundice;
gynecomastia;
Testicular atrophy
swelling of the legs (with ascites);
Cruvelier-Baumgarten noise (vascular noise over the abdomen associated with the functioning of venous collaterals);
Dupuytren's contracture, more typical for alcoholic genesis of liver cirrhosis;
changes in the terminal phalanges of the fingers according to the type of drumsticks;
atrophy of skeletal muscles, lack of pilosis on the pubis and in the armpits (in men);
Enlargement of the parotid salivary glands (typical for patients suffering from alcoholism);
hepatic odor occurs (with decompensation of liver function, precedes the development of hepatic coma and accompanies it);
flapping tremor
bruising and other manifestations of hemorrhagic syndrome;
aphthae, ulcers in the oral cavity;
Hepatomegaly or reduction of the liver, splenomegaly.

Diagnostics

List of basic and additional diagnostic measures.

The main (mandatory) diagnostic examinations carried out at the outpatient level:

· OAM;
Biochemical blood test (AST, ALT, GGTP, alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin, albumin, serum iron, total cholesterol, creatinine, glucose, sodium, potassium, ferritin, ceruloplasmin);
Coagulogram (INR, PV);
ANA; AMA;
Alpha-fetoprotein (AFP);
· Hepatitis B, C, D markers: HBsAg; anti-HCV; anti-HDV;

HIV marker;
Determination of the blood group;
Determination of the Rh factor;
ECG;
Ultrasound examination of the abdominal organs;
EGDS;
· Number linking test.

Additional diagnostic examinations performed at the outpatient level:
The average volume of erythrocytes (for the purpose of differential diagnosis of alcoholic liver damage);
The average content of hemoglobin in the erythrocyte (for the purpose of differential diagnosis of anemia);
feces for occult blood;
protein electrophoresis (gamma globulin);
Biochemical analysis of blood (total protein, OZhSS, blood ammonia, urea);
coagulogram (PTI, APTT, fibrinogen, D-dimer);
Determination of hepatitis B markers: HBeAg, anti-HBcorIgM, anti-HBcorIgG, anti-HBs, anti-HBe;
· Α 1 -antitrypsin;
Immunoglobulin G;
Immunoglobulin A;
Immunoglobulin M;
Immunoglobulin E;
antibodies to double-stranded DNA;
Antibodies to smooth muscles
· antibodies to hepato-renal microsomes anti-DL 1 ;
Thyroid hormones: T4 free, TSH, antibodies to thyroid peroxidase;
The content of cryoglobulins;
Doppler study of the vessels of the liver and spleen;
CT or MRI of the abdominal organs with intravenous contrast enhancement;
Ultrasound of the pelvic organs;
echocardiography;
indirect elastography of the liver.

The minimum list of examinations that must be carried out upon referral for planned hospitalization: in accordance with the internal regulations of the hospital, taking into account the current order of the authorized body in the field of healthcare.

Basic (mandatory) diagnostic examinations carried out at the hospital level:
KLA with the determination of the level of platelets;
Biochemical blood test (AST, ALT, GGTP, alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin, serum albumin, serum iron, total cholesterol, creatinine, glucose, ferritin; serum sodium / potassium concentration);
Coagulology: (PV, INR);
Alpha-fetoprotein (AFP);
Determination of hepatitis B, C, D markers: HBsAg, HBeAg, anti-HBcIgM, anti-HBcIgG, anti-HBs, anti-HBe; anti-HCV; anti-HDV*;
· When SH markers are detected: appropriate virological studies: PCR: HCV-RNA - qualitative analysis; HBV-DNA - qualitative analysis; HDV-RNA - qualitative analysis; HBV-DNA - determination of viral load; HCV-RNA - determination of viral load; determination of the HCV genotype; HDV-RNA - determination of viral load;
Determination of the blood group;
Determination of the Rh factor;
ECG;
Ultrasound of the abdominal organs;
Doppler study of the vessels of the liver and spleen;
EGDS;
· Test linking numbers;
Abdominal paracentesis in a patient with newly diagnosed ascites in order to examine the ascitic fluid and identify the causes of ascites (LE-A).

Additional diagnostic examinations carried out at the hospital level:
The average volume of erythrocytes;
The average content of hemoglobin in the erythrocyte;
· OAM; Nechiporenko test, daily proteinuria;
Feces for occult blood;
Biochemical analysis of blood (ammonia, total protein, ceruloplasmin, OZHSS, urea);
Protein electrophoresis (gamma globulin);
· Coagulology: activated partial thromboplastin time, prothrombin index, fibrinogen;
HIV marker;
Immunoglobulin G;
Immunoglobulin A;
Immunoglobulin M;
Immunoglobulin E;
ANA;
AMA;
· Antibodies to double-stranded DNA;
· Antibodies to smooth muscles;
· Anti-LKM1; anti-LC1;
The content of thyroid hormones: free T4, TSH, antibodies to thyroid peroxidase;
α1-antitrypsin;
The content of cryoglobulins;
CRP, procalcitonin (if bacterial infections are suspected)
Examination of ascitic fluid (cellular composition, determination of albumin gradient);
Cultural studies before ABT in case of suspected AF infection;
· Blood cultures (should be done in all patients with suspected SBP) (LE-A1);
colonoscopy;
CT or MRI of the abdominal organs with intravenous contrast enhancement;
Ultrasound examination of the small pelvis;
CT/MRI of the pelvic organs;
echocardiography;
· Indirect elastography of the liver;
· EEG;
CT / MRI of the brain (in cases of suspicion of other causes of encephalopathy: subdural hematoma, trauma, etc.);
Diagnostic paracentesis;
When examining a planned liver transplant:
- Determination of antibodies of the IgM class to the capsid antigen of the Epstein-Barr virus; antibodies of the IgG class to the capsid antigen of the Epstein-Barr virus; Epstein-Barr virus, determination of DNA (EpsteinBarrvirus, DNA) in blood serum when preparing a patient for LT;
- Determination of the avidity of anti-CMV IgG, IgG class antibodies to cytomegalovirus, IgM class antibodies to cytomegalovirus), cytomegalovirus DNA when preparing a patient for LT;
- Determination of IgG class antibodies to herpes simplex virus types 1 and 2, IgM class antibodies to herpes simplex virus types 1 and 2, PCR to determine the DNA of human herpes virus types 1 and 2 in preparing the patient for LT;
- Sowing on the microflora and determining sensitivity to an extended spectrum of antimicrobial drugs from the nasopharynx, genital secretions (vagina), urine.

Diagnostic measures taken at the stage of emergency care: are not carried out.

Instrumental research.
Ascites. In order to diagnose ascites, the main method is an ultrasound examination of the abdominal cavity.
Additional (differential) methods include:
Ultrasound of the pelvic organs: detection of formations;
CT / MRI of the abdominal organs with intravenous contrast: detection of formations of the liver, pancreas, kidneys;
· CT/MRI of the pelvis: detection of ovarian or prostate masses.

The most accessible are psychometric tests (handwriting disorders, tests of the connection between numbers and letters). In order to evaluate PE, the working group of the 11th World Congress of Gastroenterology test recommended the Number Connection Test (NCT, Number Connection Test) or the Reitan test, the interpretation of which is presented in Table 15. The disadvantages of this test are its acceptability for assessing moderate PE, time costs and non-specificity .

Table number 15. Interpretation of Number Link Test Results

Methods of instrumental diagnostics of PE are additional and include:
· Electrophysiological tests of PE: 2-sided synchronous decrease in frequency, then a decrease in the amplitude of the waves, then the appearance of three-phase potentials (PE III) disappearance of the normal α-rhythm;
· Estimation of the critical flicker frequency. The method is based on the fact that changes in retinal glial cells are similar to those in brain astrocytes. Electrical signals of synchronous nerve impulses are recorded in response to afferent stimuli: visual, somatosensory, acoustic, requiring the participation of the intellect (N - P300 peak);
CT scan of the brain, which is indicated in cases of suspicion of other causes of encephalopathy (subdural hematoma, trauma, etc.) and allows you to assess the presence, localization and severity of cerebral edema.
MRI of the brain, which is more accurate in detecting cerebral edema. Characterized by an increase in signal intensity in the basal ganglia on T 1 -weighted images.

Varicose veins of the esophagus and stomach. The main method for diagnosing VRV of the esophagus and stomach is EGDS. In the initial absence of VRV in patients with cirrhosis or stage F4, established by elastometry, mandatory screening for VRV should be performed at least once every 2 years.
Risk stratification of the presence of VRV and, accordingly, the need for endoscopy, can be carried out according to the results of indirect elastography and determination of the level of platelets in peripheral blood. For liver stiffness< 20 кПа и уровня тромбоцитов >150,000 the patient has a very low risk of having a VRV requiring treatment (1b; A). In this category of patients, it is necessary to regularly monitor the indicators of indirect elastography and platelet levels. If liver stiffness ˃ 20 kPa and platelet count< 150 000, то пациенту необходимо проведение ЭГДС.
When VRV is detected, it is necessary, in accordance with the accepted classification (Table 12), to assess the possible risks of bleeding (depending on the shape, size, color of the veins, the presence of red marks) and the need for their endoscopic ligation. The conclusion of the specialist who conducted the EGDS, which does not contain a description of these classification features, is considered incorrect and requires a second qualified study.
Intrahepatic venous pressure gradient (HVPG) is recommended to predict the risk of bleeding from VRV of the esophagus and stomach. Bleeding from varicose veins is likely when HVPG ≥ 12 mmHg, value greater than 20 mmHg. indicates difficulty in controlling bleeding, a high risk of rebleeding, and an increased risk of death from acute bleeding from a VRV.

Thrombosis of VV and SV. The main diagnostic method is a Doppler study of the vessels of the liver and spleen, which allows to assess the direct signs of acute (presence of thrombotic masses in the lumen of the vessel) or chronic thrombosis (presence of cavernosis, collaterals), as well as to measure portal blood flow, determine its type and vascular patency.

Hepatocellular carcinoma of HCC. Instrumental diagnostics is carried out according to the relevant protocol and includes ultrasound of the abdominal organs, 3 (4)-phase CT or MRI with contrast enhancement, liver biopsy (if indicated).

Indications for expert advice:
· Interventional Radiologist / Endovascular Surgeon: for TIPS, partial splenic artery embolization, HCC chemoembolization, radiofrequency or microwave ablation;
· Surgeon, transplant surgeon, endoscopist: to perform minimally invasive and surgical interventions, to determine the possibility and expediency of liver transplantation;
Oncologist: to verify the diagnosis and determine the method of treatment of HCC, other formations of OBP and MT;
· Hematologist: for the purpose of differential diagnosis;
· Ophthalmologist: slit lamp examination to detect Kaiser-Fleischer rings;
Cardiologist: in congestive CHF for the treatment of the underlying disease that led to cardiac cirrhosis;
· Psychiatrist: for alcohol dependence, as well as hepatic encephalopathy for differential diagnosis with psychiatric pathology, in determining contraindications to antiviral therapy;
· Neurologist: for the purpose of differential diagnosis of hepatic encephalopathy;
· Otorhinolaryngologist: with the development of lesions of the oral cavity, in preparing the patient for LT;
Dentist: for the purpose of rehabilitation, in preparing the patient for LT.

Laboratory diagnostics

Laboratory research.
Ascites. If a patient has ascites for the first time, abdominal paracentesis is recommended to examine the ascitic fluid and identify the causes of ascites (level A1) . When the diagnosis is established, diagnostic paracentesis is performed according to indications.
Mandatory study of ascitic fluid includes:
1) Cellular composition:
The number of erythrocytes (if it exceeds 10,000 / ml, it can be assumed that the patient has malignant neoplasms or traumatic injuries)
The number of leukocytes and polymorphonuclear leukocytes (PMNL) (with an increase of more than 500 and 250 cells / mm3, respectively, the presence of bacterial peritonitis can be assumed)
The number of lymphocytes (lymphocytosis is a sign of tuberculous peritonitis or peritoneal carcinomatosis)
2) total protein (for the purpose of differential diagnosis of transudate and exudate);
3) albumin to calculate the albumin gradient
(serumalbumin-ascitesgradient, SAAG) is calculated using the following formula: Albumin gradient \u003d serum albumin - albumin AF
Gradient ≥ 11 g/l indicates portal hypertension
gradient<11 г/лсвидетельствует о других причинах асцита
4) Cultural studies (if bacterial peritonitis is suspected).

Spontaneous bacterial peritonitis (SPB). Laboratory studies, in addition to general clinical tests, CRP, also include the study of ascitic fluid. Depending on the results of this study, several variants of SPB are distinguished (Table 14).

Table 14. SBP options according to the results of the study of AF

Differential Diagnosis

Differential Diagnosis: The CPU is shown in Table 16.

Table 16. Differential diagnosis of cirrhosis (other causes of portal hypertension)

Treatment abroad

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Treatment

Treatment goals:
Elimination of the etiological factor in order to achieve regression or stop the progression of the disease;
Prevention of the development of complications of cirrhosis and HCC;
Correction of complications of liver cirrhosis (prevention of bleeding from VRV, treatment of acute bleeding, secondary prevention of rebleeding, prevention and treatment of ascites, prevention or treatment of SBP, prevention or treatment of hepatic encephalopathy, HRS, HCC)
Improving the quality and duration of life;
· Preparation for TP.

Treatment tactics:

Non-drug treatment:
Mode:
a ban on smoking;
limitation of physical activity in patients with decompensated liver disease and in the presence of varicose veins of the gastrointestinal tract.
Diet:
Prohibition of alcohol consumption;
· Principles of rational nutrition;
· Consumption of coffee without sugar and milk up to 2-3 cups per day (with satisfactory tolerance);
Restriction of table salt (in patients with edematous-ascitic syndrome - up to 2 g / day, i.e. up to the amount contained in food in its natural form without adding salt during cooking or after it, which in practice actually means "salt-free diet")
Recommendations specific to a particular etiology of cirrhosis (eg, avoidance of copper-containing foods in Wilson-Konovalov disease; exclusion of easily digestible carbohydrates in non-alcoholic steatohepatitis with diabetes or insulin resistance, etc.);
Recommendations specific to a particular complication of cirrhosis (eg, salt-free diet for ascites, fluid restriction for hyponatremia below 120 mmol/l in the setting of edematous-ascitic syndrome, protein restriction in patients with severe encephalopathy who have TIPS or other porto-systemic shunts, etc. .d.).

Medical treatment provides:
Revision of all therapy received by the patient, with the abolition of hepatotoxic drugs;
Etiotropic therapy (for example, antiviral therapy for viral etiology of cirrhosis or abstinence for alcohol etiology, which in many cases helps to slow down the progression and even regress of the disease) (Table 17);
Basic pathogenetic therapy (for example, prednisolone and azathioprine in cirrhosis in the outcome of autoimmune hepatitis, D-penicillamine in cirrhosis in the outcome of Wilson-Konovalov's disease, ursodeoxycholic acid in primary biliary cirrhosis, ademetioinine in alcoholic cirrhosis, phlebotomy and desferal in hemochromatosis, which in many cases helps to slow down the progression of the disease and increase the survival of patients) (Table 17);
Therapy of complications of cirrhosis, as well as their primary and secondary prevention;
· Prevention of infections: viral hepatitis, bacterial infections (sepsis, meningitis, pneumonia and others) SARS through vaccination, as well as timely antibiotic therapy.

Table 17. Etiotropic and basic pathogenetic therapy for cirrhosis(LE A-B)

Drugs (active substances) used in the treatment

Groups of drugs according to ATC used in the treatment

Hospitalization

Indications for hospitalization indicating the type of hospitalization

Indications for planned hospitalization:
determination of the severity and etiology of liver damage (including biopsy);
correction of decompensated liver disease;
Prevention and treatment of cirrhosis complications (including therapeutic, endoscopic and surgical methods);
Conducting etiotropic (antiviral and other), pathogenetic (immunosuppressive and other) therapy and correction of its side effects;
Examination in preparation for liver transplantation.

Indications for emergency hospitalization:
Bleeding from VRV;
progressive hepatic encephalopathy;
hepatorenal syndrome;
· spontaneous bacterial peritonitis;
Acute thrombosis in the portal / inferior vena cava system;
Rapid progression of symptoms of decompensation.

Prevention

Preventive actions: listed in sections.

Further management.
Patients with cirrhosis are often subject to lifelong treatment and mandatory follow-up to assess the effectiveness of etiotropic therapy (if any), compensation for liver disease, prevention and correction of complications, and screening for HCC.
At least every 3 months for cirrhosis of viral etiology, and at least every 6 months for cirrhosis of non-viral etiology (including after successful antiviral therapy), the following studies are carried out:
KLA with platelet count;
biochemical blood test (ALT, AST, GGTP, alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin, albumin, creatinine, urea, glucose, total cholesterol);
Coagulogram (INR or PV);
· AFP;
· Ultrasound of the OBP;
Diagnostic EGDS:
- At least every 2 years in the initial absence of VRV and compensated liver disease;
- At least once a year with the initial presence of VRV and / or decompensated liver disease;
Investigations required for a specific complication (eg, blood electrolytes for diuretic therapy for ascites, chest x-ray for hydrothorax, other studies as indicated)
Investigations necessary for a specific etiology of LC (for example, virological diagnosis in CH, the level of copper or ceruloplasmin in the blood in Wilson-Konovalov disease, etc.);

With the progression and decompensation of cirrhosis, the frequency of control of studies may be greater (according to indications).

Information

Sources and literature

1. Minutes of the meetings of the Expert Council of the RCHD MHSD RK, 2015
   1. List of used literature: 1. Practical recommendations of the World Gastroenterological Organization: Varicose veins of the esophagus, June 2008. 2. Diseases of the liver and biliary tract. A guide for doctors / Edited by V.T. Ivashkin. -M.: Publishing House "M-Vesti", 2002. 3. Bueverov A.O. Infectious complications of liver cirrhosis// Rus. Honey. Journal. - 1998. - V.6, No. 19.- P. 15 - 19. 3. Ivashkin V.T. On the state of the organization of medical care for patients with diseases of the digestive system in the Russian Federation: Report to the board at the Ministry of Health of the Russian Federation / / Ross. journal gastroenterol., hepatol., coloproctol. - 2004. - T. 14. No. 3. -FROM. 4 – 9. 4. Fedosina E.A., Maevskaya M.V. Spontaneous bacterial peritonitis. Clinic, diagnosis, treatment, prevention// Ross. journal gastroenterol., hepatol., coloproctol. - 2007. - T. 17. No. 2. -FROM. 4 – 9. 5. Maevskaya M.V., Fedosina E.A. Treatment of complications of liver cirrhosis. Guidelines for physicians, edited by Academician of the Russian Academy of Medical Sciences, Professor V.T. Diseases of the liver according to Schiff. Cirrhosis of the liver and its complications. Liver transplantation// -M.: Publishing House "GEOTAR-Media", 2012 7. Gastroenterology. Guide edited by acad. RAMS V.T. Ivashkina, Ph.D. honey. Sciences T.L. Lapina - M .: Publishing House "GEOTAR-Media", 2008. -S. 657-676. 8. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis // J.Hepatol. – 2010.-Vol. 53(3)-P.397-417. 9. Pugh R. N. H., Murray-Lyon Im., Dawson J. L. et al. Transection of the esophagus in bleeding esophageal varices // Br. J. Surg. 1973. V. 60. P. 648–652. 10. Sen S., Williams R., Jalan R. The pathophysiological basis of acute-on-chronic liver failure // Liver. 2002. 22 (Suppl. 2): 5–13. 11. D'Amico G, Garcia-Pagan JC, Luca A, Bosch J. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. gastroenterology. 2006;131:1611–1624. 12. Feu F, García-Pagán JC, Bosch J, Luca A, Terés J, Escorsell A, Rodés J. Relationship between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet. 1995;346:1056–1059. 13. Christophe Hézode, Helene Fontaine, Celine Dorival et al. Effectiveness of Telaprevir or Boceprevir in Treatment-Experienced Patients With HCV Genotype 1 Infection and Cirrhosis //Gastroenterology. 2014. 147(1):132–142. 14. EASL Clinical Practice Guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis, 2010. ;AASLD Practice Guideline “Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012 15. Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. Roberto de Franchis, on behalf of the Baveno VI Faculty. Journal of Hepatology 2015 vol. 63j743–752. 16. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases American Association for the Study of Liver Diseases European Association for the Study of the Liver Journal of Hepatology, Vol. 61, Issue 3. 17. Endoscopic treatment of esophageal varices in patients with liver cirrhosis//Christos Triantos and Maria Kalafateli// World J Gastroenterol. 2014 Sep 28; 20(36): 13015–13026. Published online 2014 Sep 28. doi: 10.3748/wjg.v20.i36.13015 18. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. hepatology. 2007;46:922–938 18. The Modern Management of Hepatic Encephalopathy, J. S. Bajaj Disclosures Aliment PharmacolTher. 2010; 31(5):537-547) 19. Jose M. Mato, Javier Camara, Javier Fernandez de Paz, Llorenc Caballeria et al. S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. Journal of Hepatology 1999; 30:1081-1089. 20. Non-cirrhotic portal hypertension – Diagnosis and management, Rajeev Khanna, Shiv K. Sarin// Journal of Hepatology 2014, vol. 60j 421–441.

Information

List of protocol developers:
1) Kaliaskarova Kulpash Sagyndykovna - Doctor of Medical Sciences,
Professor of JSC "National Scientific Center of Oncology and Transplantation", Chief Freelance Hepatologist/Gastroenterologist of the Ministry of Health and Social Development of the Republic of Kazakhstan, Deputy Chairman of the Kazakh Association for the Study of the Liver, Astana.
2) Nersesov Alexander Vitalievich - Doctor of Medical Sciences, Professor, Head of the Department of Gastroenterology and Hepatology of the RSE on REM "Research Institute of Cardiology and Internal Diseases" of the Ministry of Health and Social Development of the Republic of Kazakhstan, Chairman of the Kazakh Association for the Study of the Liver, Almaty;
3) Dzhumabayeva Almagul Erkinovna - Master of Medicine, Assistant of the Department of Gastroenterology and Hepatology of the Republican State Enterprise on the REM "Research Institute of Cardiology and Internal Diseases" of the Ministry of Health and Social Development of the Republic of Kazakhstan, Secretary of the Kazakh Association for the Study of the Liver, Almaty;
4) Aliya Anapyarovna Konysbekova - leading specialist hepatologist / gastroenterologist of JSC "Republican Diagnostic Center", Astana
5) Tabarov Adlet Berikbolovich - Head of the Department of Innovation Management, Clinical Pharmacologist, RSE on REM "Hospital of the Medical Center of the Administration of the President of the Republic of Kazakhstan", Astana.

Conflict of interests: missing.

Reviewer: Tashenova Lyailya Kazisovna - Doctor of Medical Sciences, Head of the Hepato-Gastroenterological Center, Almaty.

Indication of the conditions for revising the protocol: revision of the protocol 3 years after its publication and from the date of its entry into force and / or in the presence of new methods with a high level of evidence.

Attached files

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What is biliary cirrhosis of the liver?

Biliary cirrhosis of the liver is a chronic disease of the organ, which is formed against the background of lesions of the biliary tract. Doctors distinguish between primary and secondary forms of the disease. Primary is the biliary cirrhosis, which is the result of autoimmune processes, first leading to cholestasis and only after a long time - to cirrhosis. The secondary form of the disease develops as a result of a violation of the outflow of bile in the large bile ducts.

The disease most often affects people of working age (from 25 to 55 years), this type of cirrhosis accounts for one case out of 10. In women, the primary form of the disease predominates, while in men the secondary one. The disease is rare in children.

Life expectancy with biliary cirrhosis

The life expectancy of a patient with biliary cirrhosis depends on the stage at which the disease was diagnosed. Often people live with this disease for 20 years or more without even knowing they have biliary cirrhosis. After the onset of the first clinical symptoms, life expectancy is about 8 years. On average, 50% of patients die 8 years after the onset of the disease, although much depends on the level of hyperbilirubinemia.

However, it is impossible to predict the life expectancy of a particular patient in absentia, since a number of factors that are individual for each patient influence the course of the disease.

It is advisable to group symptoms according to the primary and secondary forms of the disease.

So, primary biliary cirrhosis is characterized by:

The secondary form of the disease is characterized by the following features:

Increased skin itching, which even in the initial stages of the development of the disease causes serious discomfort;

Pain in the right hypochondrium, while the liver is compacted and painful on palpation and without;

The skin and mucous membranes of the mouth and eyes turn yellow, the urine darkens, and the feces become discolored;

Body temperature exceeds 38 degrees;

Complications of cirrhosis of the liver occur much earlier, in particular, we are talking about portal hypertension and liver failure.

Causes of biliary cirrhosis

Doctors have established the fact that the primary form of the disease does not have an infectious nature. Therefore, the main reason is considered to be malfunctions of the immune system and the production of specific antibodies that are aggressive towards the intrahepatic biliary tract. Also, the role of genetic predisposition to the occurrence of primary biliary cirrhosis is not denied. It is possible that diseases such as autoimmune thyroiditis, scleroderma, rheumatoid arthritis also affect.

The development of a secondary form of the disease leads to:

bile duct cyst;

Chronic pancreatitis and the narrowing of the bile duct caused by it;

Sclerosing or purulent cholangitis;

Congenital anomalies of the biliary tract;

Enlargement of lymph nodes and clamping of the bile ducts.

Treatment of biliary cirrhosis

The treatment regimen will depend on which form of the disease is diagnosed in the patient. If he suffers from primary biliary cirrhosis, then therapy should be aimed at reducing the concentration of bilirubin in the blood, at reducing the level of cholesterol and alkaline phosphatase. This is facilitated by the intake of ursodeoxycholic acid. In addition, the patient is prescribed colchicine (to prevent the development of complications of the disease) and methotrexate (to provide an immunomodulatory effect). If the disease has already led to the development of connective tissue in the liver, then antifibrotic drugs are prescribed.

In addition, the patient needs to improve the quality of life and get rid of the accompanying symptoms of the disease. To relieve itching, it is recommended to take Colestipol, Naloxin, antihistamines. To lower cholesterol levels, it is advisable to take statins. If the patient develops ascites, then the use of diuretics is necessary. With the formation of serious complications, a transplantation of a donor organ is necessary.

If a patient is diagnosed with a secondary form of the disease, then first of all he needs to normalize the outflow of bile. This is done either through endoscopy or through surgery. When it is not possible to implement such manipulations, the patient is prescribed antibiotic therapy to stop the progression of the disease.

In addition, patients need to follow a special diet. Doctors recommend adopting diet table number 5. It involves limiting the intake of fats, salt and proteins. The basic principle of nutrition is fractional, food is taken in small portions.

Primary biliary cirrhosis of the liver- a chronic progressive destructive-inflammatory process of autoimmune genesis, affecting the intrahepatic bile ducts and leading to the development of cholestasis and cirrhosis. Primary biliary cirrhosis of the liver is manifested by weakness, pruritus, pain in the right hypochondrium, hepatomegaly, xanthelasma, jaundice. Diagnosis includes the study of the level of liver enzymes, cholesterol, antimitochondrial antibodies (AMA), IgM, IgG, morphological examination of the liver biopsy. Treatment of primary biliary cirrhosis of the liver requires immunosuppressive, anti-inflammatory, antifibrotic therapy, and the intake of bile acids.

Primary biliary cirrhosis of the liver

Primary biliary cirrhosis develops predominantly in women (the ratio of affected women and men is 10:6), the average age of patients is 40-60 years. Unlike secondary biliary cirrhosis, in which there is obstruction of the extrahepatic bile ducts, primary biliary cirrhosis occurs with gradual destruction of the intrahepatic interlobular and septal bile ducts. This is accompanied by a violation of bile secretion and retention of toxic products in the liver, leading to a progressive decrease in the functional reserves of the organ, fibrosis, cirrhosis and liver failure.

Causes of primary biliary cirrhosis

The etiology of primary biliary cirrhosis is unclear. The disease often runs in families. The noted relationship between the development of primary biliary cirrhosis of the liver and histocompatibility antigens (DR2DR3, DR4, B8), characteristic of an autoimmune pathology. These factors indicate the immunogenetic component of the disease, which determines hereditary predisposition.

Primary biliary cirrhosis of the liver occurs with systemic damage to the endocrine and exocrine glands, kidneys, blood vessels and is often combined with diabetes mellitus, glomerulonephritis, vasculitis, Sjögren's syndrome, scleroderma, Hashimoto's thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, celiac disease, myasthenia gravis, sarcoidosis . Therefore, primary biliary cirrhosis of the liver is the focus of attention not only in gastroenterology, but also in rheumatology.

In the development of primary biliary cirrhosis of the liver, the starting role of bacterial agents and hormonal factors that initiate immune responses is not excluded.

Stages of primary biliary cirrhosis of the liver

In accordance with the ongoing histological changes, 4 stages of primary biliary cirrhosis of the liver are distinguished: ductal (the stage of chronic non-purulent destructive cholangitis), ductullary (the stage of proliferation of intrahepatic ducts and periductal fibrosis), the stage of stromal fibrosis and the stage of cirrhosis.

The ductal stage of primary biliary cirrhosis of the liver proceeds with inflammation and destruction of the interlobular and septal bile ducts. The microscopic picture is characterized by the expansion of the portal tracts, their infiltration by lymphocytes, macrophages, eosinophils. The lesion is limited to the portal tracts and does not extend to the parenchyma; there are no signs of cholestasis.

In the ductular stage, corresponding to the proliferation of cholangiols and periductal fibrosis, there is a spread of lymphoplasmacytic infiltration into the surrounding parenchyma, a decrease in the number of functioning intrahepatic ducts.

In the stage of stromal fibrosis, against the background of inflammation and infiltration of the hepatic parenchyma, the appearance of connective tissue strands connecting the portal tracts, progressive reduction of the bile ducts, and increased cholestasis are noted. There is a necrosis of hepatocytes, the phenomena of fibrosis in the portal tracts are growing.

In the fourth stage, a detailed morphological picture of liver cirrhosis develops.

Symptoms of primary biliary cirrhosis of the liver

The course of primary biliary cirrhosis can be asymptomatic, slow and rapidly progressive. With an asymptomatic course, the disease is detected on the basis of changes in laboratory parameters - an increase in the activity of alkaline phosphatase, an increase in cholesterol levels, and the detection of AMA.

The most typical clinical manifestation of primary biliary cirrhosis is pruritus, which precedes the appearance of icteric staining of the sclera and skin. Skin itching can bother for several months or years, so often patients are unsuccessfully treated by a dermatologist all this time. The disturbing itching leads to multiple scratching of the skin of the back, arms and legs. Jaundice usually develops 6 months to 1.5 years after the onset of pruritus. Patients with primary biliary cirrhosis have pain in the right hypochondrium, hepatomegaly (the spleen is most often not enlarged).

Hypercholesterolemia quite early leads to the appearance of xanthoma and xanthelasma on the skin. Skin manifestations of primary biliary cirrhosis of the liver also include spider veins, "liver" palms, palmar erythema. Sometimes develop keratoconjunctivitis, arthralgia, myalgia, paresthesia of the extremities, peripheral polyneuropathy, change in the shape of the fingers like "drumsticks".

In the advanced stage of primary biliary cirrhosis of the liver, subfebrile condition appears, jaundice increases, deterioration of health, exhaustion. Progressive cholestasis causes dyspeptic disorders - diarrhea, steatorrhea. Complications of primary biliary cirrhosis of the liver can be cholelithiasis, duodenal ulcers, cholangiocarcinomas.

In the late stage, osteoporosis, osteomalacia, pathological fractures, hemorrhagic syndrome, esophageal varicose veins develop. The death of patients occurs from hepatocellular insufficiency, which can be provoked by portal hypertension, gastrointestinal bleeding, asystitis.

Diagnosis of primary biliary cirrhosis of the liver

Early diagnostic criteria for primary biliary cirrhosis are changes in blood biochemical parameters. In the study of liver samples, an increase in the activity of alkaline phosphatase, the level of bilirubin, aminotransferases, and an increase in the concentration of bile acids are noted. An increase in the content of copper and a decrease in the level of iron in the blood serum are characteristic. Already in the early stages, hyperlipidemia is determined - an increase in the level of cholesterol, phospholipids, b-lipoproteins. Of decisive importance is the detection of a titer of antimitochondrial antibodies above 1:40, an increase in the level of IgM and IgG.

According to the ultrasound of the liver and MRI of the liver, the extrahepatic bile ducts were not changed. To confirm primary biliary cirrhosis, a liver biopsy with a morphological study of the biopsy is indicated.

Primary biliary cirrhosis of the liver is differentiated from diseases that occur with obstruction of the hepetobiliary tract and cholestasis: strictures, liver tumors, calculi, sclerosing cholangitis, autoimmune hepatitis, intrahepatic duct carcinoma, chronic viral hepatitis C, etc. In some cases, for the purpose of differential diagnosis, they resort to carrying out biliary tract ultrasonography, hepatobiliary scintigraphy, percutaneous transhepatic cholangiography, retrograde cholangiography.

Treatment of primary biliary cirrhosis of the liver

Therapy for primary biliary cirrhosis of the liver includes the appointment of immunosuppressive, anti-inflammatory, antifibrotic drugs, bile acids. The diet for primary biliary cirrhosis of the liver requires sufficient protein intake, maintaining the required calorie content of food, and limiting fats.

Pathogenic therapy drugs include glucocorticosteroids (budesonide), cytostatics (methotrexate), colchicine, cyclosporine A, ursodeoxycholic acid. Long-term and complex administration of drugs can improve blood biochemical parameters, slow down the progression of morphological changes, the development of portal hypertension and cirrhosis.

Symptomatic therapy of primary biliary cirrhosis of the liver includes measures aimed at reducing itching (UVR, sedatives), bone loss (vitamin D, calcium supplements), etc. In cases of primary therapy refractory forms of primary biliary cirrhosis, as early as possible transplantation is indicated liver.

Prognosis of primary biliary cirrhosis of the liver

With asymptomatic primary biliary cirrhosis, life expectancy is 15-20 years or more. The prognosis in patients with clinical manifestations is much worse - death from liver failure occurs within about 7-8 years. The development of ascites, varicose veins of the esophagus, osteomalacia, hemorrhagic syndrome significantly aggravates the course of primary biliary cirrhosis of the liver.

After liver transplantation, the probability of recurrence of primary biliary cirrhosis reaches 15-30%.

Biliary cirrhosis of the liver - what is it? Symptoms and treatment

One of the unpleasant diseases of the liver, which is accompanied by a violation of its functioning, is biliary cirrhosis. With such a pathology, destruction of the structure of the organ is observed as a result of failures in the outflow of bile, as well as changes in the structure of the bile ducts. Biliary cirrhosis of the liver is divided into two types: primary and secondary. Usually this disease is diagnosed in middle-aged people, however, most often it is detected after 50-60 years.

The onset of the disease is characterized by developing hepatocellular insufficiency, which subsequently develops to portal hypertension. The prognosis for the development of the disease can be favorable if the cause of bile stasis is eliminated. If this is not possible due to insufficiently qualified doctors or due to the individual characteristics of each person, severe liver failure develops with a violation of most of its functions. The result is an inevitable death.

What it is?

Biliary cirrhosis of the liver (BCP) is a disease in which, for various reasons, the patency of the bile ducts is impaired, due to which the outflow of bile into the intestine decreases or stops. According to etiology, primary and secondary forms of the disease are distinguished.

Reasons for development

It has not yet been possible to establish the specific cause of the formation of biliary cirrhosis. Some theories of its formation are considered:

It is currently impossible to confirm a direct link between these conditions and the formation of cirrhosis.

First, under the influence of certain causes, lymphocytes begin to destroy the cells of the bile ducts - an inflammatory process is formed in them. Due to inflammation, the patency of the ducts is disturbed and stagnation of bile develops. In these areas, damage to hepatocytes occurs and inflammation develops again. Massive cell death can lead to the formation of cirrhosis.

Classification

Primary BCP is an autoimmune disease that manifests itself as a chronic non-purulent destructive inflammation of the bile ducts (cholangitis). In the later stages, it causes stagnation of bile in the ducts (cholestasis) and eventually provokes the development of cirrhosis of the liver. Most often, women of forty to sixty years old suffer from pathology.

• In stage I, inflammation is limited to the bile ducts.
• At stage II, the process extends to the liver tissue.
• III stage. Hepatocytes - liver cells - begin to transform into connective tissue, adhesions-scars are formed, which "bring together" the bile ducts.
• Stage IV - typical cirrhosis of the liver.

Secondary biliary cirrhosis occurs against the background of a long-term violation of the outflow of bile in the intrahepatic ducts due to their narrowing or blockage caused by other diseases. It is more common in men in their 30s and 50s. Without treatment, both forms of the disease sooner or later lead to liver failure, worsening the quality of life and reducing its duration.

Symptoms of biliary cirrhosis of the liver

In the case of biliary cirrhosis, it is advisable to group the symptoms according to the primary and secondary forms of the disease.

So, primary biliary cirrhosis is characterized by:

1. Staining of the skin in a dark brown color, primarily in the area of ​​​​the shoulder blades, large joints, and later on the whole body;
2. Intermittent skin itching, which often appears during a night's rest, with additional irritating factors (for example, after contact with woolen products or after taking a bath). Itching can last for many years;
3. Enlargement of the spleen in volume is a common symptom of the disease;
4. The appearance of a flat formation on the eyelids, which looks like a plaque. There are most often several of them, xanthelasmas can also appear on the chest, palms, buttocks, elbows;
5. A person may begin to be disturbed by pain in the region of the right hypochondrium, in the muscles, in the mouth, a bitter taste often appears, and the body temperature rises slightly.

With the progression of the disease, all symptoms intensify, there is a loss of appetite, itching becomes unbearable. Areas of pigmentation coarsen, the skin swells, the terminal phalanges of the fingers thicken. Pain intensifies, varicose veins of the esophagus and stomach are observed, internal bleeding may develop. The absorption of vitamins and nutrients is difficult, symptoms of hypovitaminosis join. Lymph nodes increase, disturbances occur in the digestive system.

The secondary form of the disease has similar symptoms, including:

• severe pain in the area of ​​the affected liver;
• intense itching of the skin, aggravated at night;
• soreness of the liver on palpation and an increase in its size;
• early onset of jaundice;
• splenomegaly;
• an increase in body temperature to febrile levels against the background of a developing infection.

Quite quickly, this form of the disease leads to the development of cirrhosis and subsequent liver failure, the symptoms of which threaten the patient's life. In particular, the symptoms of liver failure in humans are:

• nausea and vomiting of intestinal contents;
• dyspeptic disorders;
• discoloration of feces and urine the color of dark beer;
• hepatic encephalopathy (dementia).

The condition can cause severe complications such as ascites, internal stomach and intestinal bleeding, coma, and death.

Diagnostics

Diagnostic measures for the detection of primary biliary cirrhosis can have several stages:

• First of all, a patient with suspected liver cirrhosis should consult with several doctors - a hepatologist, surgeon, gastroenterologist. Only they can identify the disease, determine its degree, prescribe subsequent diagnostic measures and possible treatment.
• After a medical consultation, a patient with suspected cirrhosis must be sent for laboratory tests. Investigations may include a detailed blood and urine test, as well as a biopsy.

The third stage is instrumental diagnostics. It includes an examination of the spleen, kidneys, liver, biliary tract, using ultrasound. In addition, an examination of the internal organs is carried out using an endoscope, the introduction of special substances into the blood and gastric tract, which show the real work and functioning of the liver and bile ducts.

Treatment of biliary cirrhosis

When diagnosing biliary cirrhosis, treatment methods are based on reducing the intensity of its symptomatic manifestations, slowing down further development, treating associated complications and preventing their occurrence.

The course of treatment and selection of drugs is selected individually by your doctor. Mainly prescribed:

• Ursodeoxycholic acid (urosan, ursofalk) 3 capsules at night, daily.

Immunosuppressants (only for primary biliary cirrhosis):

• Methotrexate 15 mg per week or cyclosporine at a therapeutic dosage of 3 mg per 1 kg of body weight per day, divided into 2 doses (morning and evening).

• Prednisolone 30 mg 1 time per day in the morning on an empty stomach, after 8 weeks the dose of the drug is reduced to 10 mg 1 time per day in the morning on an empty stomach.

Treatment of metabolic disorders of vitamins and minerals:

• cuprenil (D-penicillamine) 250 mg dissolved in one glass of water 3 times a day for 1.5 hours before meals;
• multivitamins (citrum, multitabs) 1 capsule 1 time per day;
• stimol 1 sachet 2 times a day.

Skin itching treatment:

• cholestyramine (questran) 4 mg 1.5 hours before meals 2-3 times a day;
• rifampin (rimactan, benemycin, tibicin) 150 mg 2 times a day;
• antihistamines (atarax, suprastin) 1-2 tablets 2-3 times a day.

In the case of secondary biliary cirrhosis, it is important to restore the normal outflow of bile. For this, endoscopy, or surgery, is prescribed. If for some reason these manipulations are impossible, antibiotics are prescribed to prevent the transition of cirrhosis to the thermal stage.

Total duration: 21:51

Alexander Sergeevich Trukhmanov, Doctor of Medical Sciences, Professor:

Let me gladly give the floor to Elena Nikolaevna Shirokova, Doctor of Medical Sciences, with the message "Modern consensus on the diagnosis and treatment of primary biliary cirrhosis and primary sclerosing cholangitis." Please, Elena.

Elena Nikolaevna Shirokova, Doctor of Medical Sciences, Associate Professor:

Thank you very much, Alexander Sergeevich.

Allow me to introduce you to the current state of the issue of diagnosis and treatment of primary biliary cirrhosis and primary sclerosing cholangitis.

First of all, let's define what primary biliary cirrhosis is. This is a chronic cholestatic liver disease, which is based on immune-mediated destruction of small intrahepatic bile ducts. A characteristic feature is the presence of antimitochondrial antibodies.

The incidence of primary biliary cirrhosis ranges from 15 to 400 cases per million population. The vast majority of patients with primary biliary cirrhosis - about 90% - are women. The average age of disease manifestation is 50 years.

Currently, almost half of patients are diagnosed with the disease in the asymptomatic stage. In the absence of adequate treatment, after 10-20 years, patients may develop cirrhosis of the liver and liver failure.

A characteristic sign of primary biliary cirrhosis is pruritus. Even more often than skin itching, weakness occurs in patients. Moreover, there is no correlation of weakness with the severity of histological manifestations, with the severity of biochemical indicators of activity, and with the age of the patient.

Half of the patients may have jaundice. The presence of concomitant autoimmune diseases, such as autoimmune thyroid disease, autoimmune thyroiditis, Raynaud's syndrome, is characteristic.

In some cases, we encounter severe hyperpigmentation of the skin, the presence of xanthelasma and xanthoma.

In 60% of patients, as a rule, the liver is enlarged. According to biochemical samples, cholestasis is determined. The presence of antimitochondrial antibodies in a titer of 1:40 or more is a characteristic feature.

As for the morphological data, the determining factor is the presence of non-purulent destructive cholangitis.

On this slide you see a photograph of our patient who suffers from primary biliary cirrhosis. Expressed xanthelasmas and xanthomas, which are less common. In about 10 patients with severe cholestasis, they are located on the back surface of the hands and at the level of the elbow. This is due to an increase in serum cholesterol levels of more than 400 mg/dl if this has been observed for more than three months.

So, what are the main diagnostic criteria for primary biliary cirrhosis. This is an increase in the level of alkaline phosphatase (AP) and gammaglutamyl transpeptidase, the presence of antimitochondrial antibodies of the M2 fraction directed to the E2 component of the pyruvate dehydrogenase complex. This is the presence of destructive cholangitis, lymphocytic infiltration.

In some cases, approximately 10 - 20 patients who suffer from primary biliary cirrhosis, we are faced with a situation where there are features of autoimmune hepatitis. This is the so-called phenomenon of crossover. Crossover syndrome is a combination of symptoms of both autoimmune hepatitis and primary biliary cirrhosis.

It is believed that two of the three criteria listed here for each disease must be present in order to make this diagnosis.

For primary biliary cirrhosis, these are:

• an increase in the level of alkaline phosphatase more than 2 times the upper limit of the norm, or the level of gamma-glutamyl transpeptidase more than 5 times the upper limit of the norm;
• the presence of antimitochondrial antibodies in a titer of 1:40 and above;
• the presence of non-purulent destructive cholangitis according to liver biopsy.

For autoimmune hepatitis, the presence of the following criteria:

• an increase in the level of alanineamine transaminase by more than 5 times from the upper limit of the norm;
• an increase in the level of class G immunoglobulin by more than 2 times, or the presence of antibodies in smooth muscles in a diagnostic titer of 1:80;
• according to liver biopsy, it is important to determine periportal or periseptal stepwise necrosis.

Histological preparation. This is the liver tissue of our patient who suffers from decussation syndrome (primary biliary cirrhosis and autoimmune hepatitis). There is a pronounced lymphohistocytic infiltration in the portal tract, in the center the presence of stepped necrosis. Slightly to the right, an unevenly expanded lumen of the vitelline duct (a phenomenon of proliferation of ducts).

It is well known that the drug that is officially approved in all countries for the treatment of primary biliary cirrhosis is "Ursodeoxycholic acid" (UDCA). Interesting data Pares A., which were presented in the journal "Gastroenterology" in 2006, which evaluated the impact of "Ursodeoxycholic acid" on the survival of patients with primary biliary cirrhosis.

The survival of those patients who had a good response to therapy did not actually differ from that of a similar age and population. Significantly exceeded survival, which was predicted by the Mayo model. This is the green "curve". These data are reliable, and the survival of patients with a good biochemical response is strikingly different from the survival predicted by the Mayo model. And the Mayo model is practically the main model that allows you to calculate the prognostic survival of patients with primary biliary cirrhosis.

What is considered a good biochemical response. It is customary to determine it after a year of therapy with Ursodeoxycholic acid. There are so-called Paris criteria. This means normalization of bilirubin levels. It must be less than 1 mg/dl (or less than 17 µmol/l) in the C system.

The level of alkaline phosphatase (AP) should be less than or equal to three times the normal limit. The level of aspartate aminotransferase (AST) should be less than two norms.

As for the Barcelona criteria, this is a decrease by 40% or normalization of the level of alkaline phosphatase after a year of therapy with Ursodeoxycholic acid.

We have our own experience of four years of therapy with "Ursodeoxycholic acid", the drug "Ursosan" in patients with primary biliary cirrhosis. We have shown that in terms of its effect on biochemical parameters, Ursosan is most effective in patients with the first stage of primary biliary cirrhosis. It was they who showed normalization of the level of serum transaminases and a decrease in the level of bilirubin by more than 2.5 times. Bilirubin is the main prognostic marker in patients with primary biliary cirrhosis.

The minimum therapeutic effect was noted in patients with the fourth (last) stage of the disease at the stage of liver cirrhosis, which is consistent with the data of international studies.

So, this is the strategy. Patients with primary biliary cirrhosis should receive "Ursodeoxycholic acid" at a dose of 13-15 mg/kg/day. This is the standard, officially approved therapy.

If a biochemical response is observed, which we have already discussed earlier, Ursodeoxycholic acid monotherapy should be continued under constant monitoring of the patient's condition, the level of biochemical samples.

If there is no response, and there are signs of overlap with autoimmune hepatitis, the phenomena of lobular hepatitis, an increase in the level of aspartic transaminase, or another situation, then a suboptimal biochemical response is obtained. We do not receive the full answer that we expected. This is almost a third of patients.

What to do. In this situation, a single universal strategic step has not yet been developed. Various options are suggested. One of them is the additional appointment of "Budesonide" at a dose of 3 to 9 mg per day.

The second stage drug is Mycophenolate Mofetil. This is an immunosuppressive therapy that can eliminate or reduce the side effects of corticosteroids. The suggested dose is one and a half grams per day.

If the answer is no, then the question of the possibility of using fibrates is now being considered. The duration of this course has not yet been determined. The suggested dose is 200 mg per day.

So, what recommendations for the treatment of primary biliary cirrhosis can be formulated today. According to the European Society for the Study of the Liver, it is considered that the officially approved drug is Ursodeoxycholic acid. The dose is 13-15 mg/kg/day for a long time. With a suboptimal biochemical response, a combination of "Ursodeoxycholic acid" with "Budesonide" (second-generation glucocorticoid) is possible.

As for the cross syndrome, here, perhaps, a combination of "Ursodeoxycholic acid" with corticosteroids is required. In the second option - monotherapy with Ursodeoxycholic acid.

In our clinic, headed by academician Vladimir Trofimovich Ivashkin, we have our own good experience in treating patients with the "Ursodeoxycholic acid" cross syndrome with corticosteroids.

Our patients (58 patients) were divided into 2 groups according to the variant of the overlapping syndrome. Patients with the first option took corticosteroids and Ursosan (ursodeoxycholic acid - at a standard dose of 13-15 mg/kg/day).

The second option is patients who had histological features resembling primary biliary cirrhosis. At the same time, they had antibodies in smooth muscles and antinuclear antibodies in the diagnostic titer and a fairly high biochemical activity, an increase in the level of transaminases. They received Ursosan monotherapy.

Sixty percent of our patients had a complete response, and more than a quarter showed a partial response to therapy.

When analyzing the cumulative survival of patients with overlapping syndrome, we found that the survival of patients exceeds the survival predicted by the Mayo model. The survival of our patients is the upper yellow "curve". The lower red line is the survival rate, which is predicted by the Mayo model. "Ursodeoxycholic acid" is able to improve the survival of patients with cross-syndrome.

What new directions in the treatment of primary biliary cirrhosis exist at the moment. These are farnesoid X receptor (FXR) agonists - “Obeticholic acid”. Is it 6? ethyl-chenodeoxycholic acid, which is currently in the third phase of clinical trials. Preliminarily, it can be said that it improves the biochemical tests of patients with primary biliary cirrhosis and lowers their level of serum immunoglobulin M.

And the second direction is PPAR? agonists. These are fibrates. They have anti-inflammatory and immunomodulatory properties. Currently being actively studied.

The second direction of my today's message is primary sclerosing cholangitis. It is also a chronic cholestatic liver disease characterized by diffuse inflammation and fibrosis of the intra- and extrahepatic bile ducts.

Unlike primary biliary cirrhosis, primary sclerosing cholangitis affects mainly men. The ratio of men to women is 2:1. As a rule, the disease is diagnosed in patients aged 40 years. Extremely rare in children. In 60 - 80% of cases there is a combination of primary sclerosing cholangitis with inflammatory bowel disease. 80% are patients with non-specific ulcerative colitis, 10-15% are Crohn's disease.

Various clinical variants of the debut of primary sclerosing cholangitis are possible. This may be an asymptomatic increase in liver function tests. The patient is being examined as part of a clinical examination and he has elevated markers of cholestasis syndrome.

Either this is a classic manifestation (skin itching, weakness, jaundice). Or it could be markers of recurrent bacterial cholangitis. Either the diagnosis is already at the stage of complications of cholestasis. Or at the stage of complication of portal hypertension, when the debut occurs with bleeding from varicose veins of the esophagus.

Most often, we fix an increase in the level of alkaline phosphatase. As a rule, this is a 100% finding in a biochemical blood test. Aspartic and alanine transaminases are elevated in almost 90% of patients. Gamma-glutamyltransferase in 85% of cases.

Antineutrophil cytoplasmic antibodies (ANCA) are found in 65-70% of cases (especially if the patient still has ulcerative colitis). In 60%, bilirubin may be elevated. Antibodies in smooth muscles, antinuclear factor, we meet in approximately half of the patients.

Basic diagnostic criteria for primary sclerosing cholangitis. This is the presence of chronic cholestasis, that is, an increase in the level of gamma-glutamyl transpeptidase, alkaline phosphatase, lucinaminopeptidase (LAP). These are data from endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiography. Of course, the exclusion of the causes of secondary sclerosing cholangitis.

Changes that are typical during cholangiography. This is the presence of diffuse multifacal annular strictures that alternate with areas of normal or slightly divided ducts. Presence of short, band-like strictures or saccular protrusions that resemble diverticula.

Data from endoscopic retrograde cholangiopancreatography. Arrows indicate strictures of the extrahepatic bile ducts.

Magnetic resonance cholangiogram of a 72-year-old patient suffering from primary sclerosing cholangitis. The top arrow shows the narrowing at the level of the right anterior hepatic duct, and the bottom arrow shows where the common hepatic duct should be visible. Lack of visualization suggests the presence of a stricture.

As for the data of a liver biopsy, here a typical symptom is “onion peel”. This is the presence of concentric fibrosis. But when it comes down to whether all patients need a liver biopsy, the current recommendations are: no, not all patients.

If you have no doubts about the diagnosis of primary sclerosing cholangitis, there are typical biochemical signs, typical cholangiogram data, then in this case morphological verification can wait.

If you suspect that there is a syndrome of overlap in combination with autoimmune hepatitis, or you suspect sclerosing cholangitis in the small ducts (when there are no characteristic cholangiographic findings), then liver biopsy is certainly the final word here.

"Ursodeoxycholic acid" is one of those drugs that has been intensively, actively and widely studied in the treatment of patients with primary sclerosing cholangitis. It is well known and approved for the treatment of primary biliary cirrhosis. Given the similarity of clinical manifestations, many researchers have tried this drug in the treatment of primary sclerosing cholangitis.

What features, what actions of the drug can be considered attractive. "Ursodeoxycholic acid" stimulates the processes of detoxification of bile acids, stimulates secretion, and has an apoptos-inhibiting property. In addition, it protects cholangiocytes from the toxic effects of hydrophobic bile acids. Even the antifibrotic effect of the drug is described.

Primary sclerosing cholangitis. Lindor study data from 1997. 105 patients entered the study. "Ursodeoxycholic acid" was used in a standard dose of 13-15 mg/kg for 2-5 years. An improvement in biochemical parameters has been noted in patients with primary sclerosing cholangitis. At the same time, there was no significant effect on clinical signs or survival.

Olsson data, 2006. A more representative cohort of patients, a higher dose of the drug. "Ursodeoxycholic acid" was taken at a dose of 17 - 23 mg / kg / day for five years. There was an excellent trend towards improved survival with Ursodeoxycholic Acid. However, it was not statistically significant.

According to the Mitchell pilot study, the drug was well tolerated at a dose of 20 mg/kg/day. An improvement in liver function tests was noted. In the USA, a large representative study was conducted, in which 150 patients took part. There was a higher dose of the drug (28-30 mg/kg/day). For five years, patients had to take this drug.

However, the study was terminated early because the ursodeoxycholic acid group experienced more frequent fatalities, the need for liver transplantation, or death.

There is interesting evidence that "Ursodeoxycholic acid" can reduce the risk of colorectal dysplasia in patients with primary sclerosing cholangitis and ulcerative colitis. In the experiment, it was shown that "Deoxycholic acid" stimulates the proliferation of the colorectal epithelium in animals. In turn, "Ursodeoxycholic acid" suppresses apoptosis, which is induced by "Deoxycholic acid". "Ursodeoxycholic acid" inhibits the growth of colon cancer cells that are stimulated by "Deoxycholic acid".

At the same time, there is currently no basis for broad recommendations for the unconditional intake of Ursodeoxycholic Acid in patients suffering from primary sclerosing cholangitis. With regard to the recommendations of the European Society for the Study of Liver Diseases, it is considered proven that taking the drug at a dose of 15 - 20 mg / kg / day improves liver tests and prognostic markers of the disease. However, an effect on survival has not been proven. For the prevention of colorectal cancer, the drug may be recommended in high-risk groups.

Primary biliary cirrhosis from etiology to treatment

Primary biliary cirrhosis (PBC) -

chronic progressive liver disease with a predominant lesion of the intrahepatic bile ducts and the development of chronic intrahepatic cholestasis, leading to the formation of fibrosis and cirrhosis of the liver. The disease affects predominantly young and middle-aged women (90% of patients), racial and national characteristics are not noted.

The prevalence of this disease, previously considered rare, in modern conditions is becoming very significant and amounts to 3.5-15 cases per 100 thousand population. The increase in the incidence is associated with the improvement of diagnostic methods, the possibility of conducting automated biochemical studies of cholestasis markers, as well as the determination of antimitochondrial antibodies (AMA) in the early stages of the disease.

Etiology and pathogenesis

The cause of the disease has not been elucidated. The significance of genetic predisposition, immune disorders, bacterial, viral and other antigens in the development of PBC is discussed.

In favor of the genetic mechanisms of the development of the disease, data on a higher incidence of PBC in families where there is already a patient with PBC speak. For example, in New York, in such families, the incidence of PBC is 1.3%, and in London - 5.5%. The disease can be passed from mother to daughter

Central Research Institute of Gastroenterology

and in the second generation it develops at a younger age. In confirmation of the genetic factor, data are given on the detection of AMA in 7% of relatives of patients with PBC (in the population - only in 0.5% of cases). At present, the relationship between the development of PBC and the detection of certain antigens of the major histocompatibility complex is not questioned.

Trigger factors for the immunopathological reaction in PBC can be viral (hepatotropic viruses), bacterial (enterobacteria, Helicobacter) and other antigens (AH). The frequency of detection of markers of hepatitis B, C, and B viruses in PBC is 5-17% (according to TsNIIG - 21%). But often the disease develops as a result of only a violation of immunoregulation.

The essence of the hypothesis about the trigger role of viral and bacterial antigens is as follows: it is known that there is a certain similarity between the mitochondria of mammals and bacteria. During evolution, many AGs, including the E2 antigen of the human mitochondrial inner membrane, remain highly conserved and are present in bacteria, yeast, and mammals. Cross-reactions to AG of the epithelium of the bile ducts and microorganisms are possible. Proteins sensitive to PBC-specific AMA are detected in some types of microorganisms (Escherichia, Rickettsia) and, apparently, are localized in their wall. It is possible that those found in PBC

AMAs were originally directed against enterobacteriophageal antigens that appear in intestinal infections. There is evidence of a high frequency of detection of anti-colreticulin class A immunoglobulins in patients with PBC, yersiniosis, and alcoholic liver disease, which reflects the reactivity of the intestinal immune system and suggests the presence of unknown bacterial AH, which can also be trigger factors in the development of PBC. A cross-reaction was found between Mycobacterium gordone and the E2 subunit of the pyruvate dehydrogenase complex, the main immune target for AMA in PBC, but M. gordone could not be detected in the liver tissue.

In the study of hepatobiopsy specimens, Helicobacter pylori is detected in the liver tissue in every fourth examined person with chronic cholestatic diseases. In 69% of cases, antibodies to H. pylori were found in the blood serum of patients with PBC. It can be assumed that H. pylori infection stimulates an autoimmune response in the development of PBC.

In the development and course of PBC, an important role is played by disturbances in the functional activity of the immune system, in particular, T- and B-lymphocytes that regulate cellular and humoral immune responses. The epithelium of the bile ducts is infiltrated with cytotoxic T-lymphocytes.

Great importance in the pathogenesis of PBC is given to the spectrum of produced cytokines.

new - biologically active mediators that carry out the interaction of immunocompetent cells with each other and with other cells. Various cytokines selectively stimulate cell subpopulations and the expression of membrane molecules, which is necessary for the interaction of immunocompetent cells with bile duct epithelial cells. Through cytokines, the nature, depth and

the duration of inflammation and the body's immune response. According to TsNIIG, in patients with PBC, in 76-97% of cases, a moderately elevated content of cytokines with pro-inflammatory (tumor necrosis factor a, interleukin-6, interferon-y) and anti-inflammatory properties (interleukin-4) is determined. The concentrations of these cytokines increase with an increase in the biochemical and immunological activity of the disease, which confirms their role in the maintenance and regulation of inflammation in PBC.

A possible direct mechanism of cell death in PBC is apoptosis, carried out by both T-helpers and secreted cytokines. Apoptosis is defined as a form of programmed cell death with characteristic morphological and biochemical features. The main cells undergoing apoptosis in the liver of patients with PBC are biliary epithelial cells (in contrast to hepatocytes in autoimmune hepatitis). Apoptosis of epithelial cells in the bile ducts in PBC is determined significantly more often than in primary sclerosing cholangitis (PSC) and in healthy individuals. It is possible that in PBC, in contrast to PSC, apoptosis is secondary to inflammatory cell damage.

The significance of the humoral immune response in PBC is confirmed by the high level of secretion of immunoglobulins M (IgM) and autoantibodies to various subcellular structures, primarily to mitochondria. The close association between PBC and AMA was first discovered by Wochasie! a1. in 1966. Most often, in routine practice, total AMA are determined using the method of indirect immunofluorescence (IFL), and in the last decade, a highly sensitive method of enzyme-linked immunosorbent assay (ELISA) has been developed to determine individual types of AMA. PBC is characterized

detection of antimitochondrial antibodies to the M2 antigen (AMAM2) produced against antigens located on the inner side of the mitochondrial membrane in the form of a complex of enzymes (E2 is a subunit of the pyruvate dehydrogenase complex). AMAM2 are detected in the majority of patients with PBC (85-95%) and are not organ- or species-specific. According to TsNIIG, in patients with PBC, AMAM2 was detected in peripheral blood by ELISA in 85.4% of cases, their content averaged 250.2 ± 67.8 U/ml (from 40 to 1400 U/ml). An increase in the level of AMAM2 correlated with an increase in clinical, biochemical and immunological activity, reaching a maximum at stages 3-4 of PBC, which confirms their prognostic value.

In addition to the detection of AMA in blood serum, in recent years there have been works on the determination of AMA in saliva and urine. AMA were found in saliva in 9 out of 12 PBC patients with serum AMA. In the urine, AMA were found in 71 of 83 (86%) patients with PBC and 71 of 78 (91%) patients with PBC positive for AMA. In the control group, which included 58 people with other liver diseases and healthy individuals, AMA were not found in any case. The authors suggest that the use of this method for population screening will allow detection of preclinical stages of PBC.

Clinical picture

The development of the disease is preceded by a long asymptomatic period or a course under the guise of another disease. This fact serves as the basis for distinguishing the asymptomatic stage of PBC. As a rule, there are no physical changes at this time, but a slight increase in the activity of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) can be detected in the blood. With the help of IFL

total AMA are found in a diagnostic titer of 1: 40 and above.

The disease begins imperceptibly. Patients with PBC in the early stages feel well and remain able to work for a long time. The earliest and most persistent symptoms include itching - local or diffuse, moderate or pronounced. Sometimes it is the only symptom for several months or even years. Itching can become excruciating and cause chronic insomnia in patients, which leads to fatigue, reduced performance and quality of life. In some patients, itching appears at later stages, but may be absent throughout the entire period of the disease.

Yellowness of the sclera and skin in a small number of cases precedes skin itching, but usually appears after several months or years, sometimes these symptoms occur almost simultaneously. In the early stages of the disease, jaundice can be undulating, and in the future, its steady progression is often noted.

Often, patients complain of increased fatigue and aching pain in the right hypochondrium of varying intensity.

On examination, attention is drawn to dryness and pigmentation of the skin, traces of scratching, hyperkeratosis of the skin (mainly of the lower extremities), the presence of xanthelasma on the eyelids (very rarely on the palms and elbows). Along with this, more than half of the patients at the time of the first visit to the doctor revealed hepatomegaly of varying severity (significant hepatomegaly is not typical), in a third of patients - a slight increase in the spleen. Edema, ascites, manifestations of encephalopathy are found, as a rule, in the terminal stage of the disease.

The frequency of detection of clinical symptoms (%) in patients with PBC (n = 150) during primary hospitalization at the Central Research Institute of Human Resources:

Weakness, fatigue 68.8

Weight loss 24.6

Skin itching of varying intensity 75.8

Skin changes (pigmentation, 67.2

dryness, xanthelasma, xanthomas, traces of scratching)

Yellowness of the skin 12.5

Hepatomegaly 87.7

Splenomegaly 46.7

Edema-ascitic syndrome 11.7

Combination with autoimmune 29.7

diseases and syndromes

Asymptomatic 7.0

In a laboratory study in patients with PBC, characteristic deviations of the biochemical blood test are revealed: a significant increase in the activity of alkaline phosphatase, GGTP, moderate (3-5 times) - alanine aminotransferase (AlAT) and asparaginaminotransferase (AsAT), an increase in the content of bilirubin (to varying degrees ). In the study of humoral immunity, in the vast majority of cases, a significant increase in the level of IgM is found (on average, 6.2 ± 0.6 g/l). The detection of AMAM2 is diagnostically significant. Patients with PBC often have antinuclear (ANA) and antismooth muscle (AGMA) antibodies; often determined by antiphospholipid antibodies, as well as antibodies to reticulin and endo-mysium. In a clinical blood test, moderate anemia and an increase in ESR are often noted.

Approximately one third of patients already at the time of the first visit to the doctor revealed instrumental signs of portal hypertension: splenomegaly, changes in portal blood flow, an increase in the diameter of the splenic and portal veins, varicose veins of the esophagus.

PBC often co-occurs with other autoimmune diseases and syndromes. By

according to TsNIIG, most often (31%) lung lesions in the form of fibrosing alveolitis are detected. One fifth of patients have thyroid diseases: diffuse goiter and autoimmune thyroiditis. Quite often, PBC is accompanied by rheumatoid arthritis - in 12.5%. In 1-3%, Sjögren's syndrome (dry syndrome: keratoconjunctivitis, xerophthalmia, xerostomia), Raynaud's syndrome and systemic scleroderma are found.

Long-term cholestasis leads to a deterioration in the absorption of fat-soluble vitamins, as a result of which certain complications develop. Osteoporosis is the most common (according to TsNIIG - about 15%), associated with impaired metabolism of vitamin D involved in calcium metabolism. In 10% of cases, a deficiency of fat-soluble vitamins is manifested by trophic disorders of the skin, mucous membranes, visual impairment, and polyneuropathy. Steatorrhea, which is considered characteristic in the presence of prolonged cholestasis, was noted in our observations in isolated cases.

Histological picture

Needle biopsy of the liver is of great importance in the diagnosis of PBC, especially in the asymptomatic and early stages of the disease. At the stage of liver cirrhosis, morphological changes become less specific.

The division of PBC into clinical and morphological stages is conditional. The biopsy material shows signs of at least two stages of the disease with a predominance of one of them.

At stages 1-2 of PBC, biopsy specimens reveal varying degrees of damage to the bile ducts. The earliest changes should be considered dystrophy, destruction and desquamation of the epithelium of the bile ducts (a picture of non-purulent

destructive cholangitis). Characterized by the formation of granulomas. The progression of PBC is mainly due to the degree of destruction of the intrahepatic bile ducts.

At stages 2-3, the biopsy reveals tubular proliferation, periductular fibrosis, and sclerosis with the formation of blind septa.

For the 4th stage of PBC, a picture of pronounced micronodular cirrhosis is characteristic along with signs typical of earlier stages.

In PBC, as in other diseases that occur with cholestasis, copper is deposited in the liver, but not in a toxic form. Many works in recent years have been devoted to eosinophilic infiltration of the portal tracts in PBC. Electron microscopy revealed the presence of apoptotic bodies in hepatobioptates of patients with PBC, which confirms the involvement of apoptosis processes in damage to biliary epithelial cells and hepatocytes in PBC.

Differential Diagnosis

PBC should be differentiated from autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), viral hepatitis with cholestasis (viral hepatitis C, cytomegalovirus hepatitis, etc.), alcoholic hepatitis, drug-induced liver injury, sarcoidosis, etc.

With AIH, high (8-10 times or more higher than normal) levels of AST and ALT are noted, the level of IgO increases significantly, ANA, AGMA are detected. An increase in the level of cholestasis markers is not typical.

The diagnosis of PSC is established on the basis of the characteristic pattern of retrograde cholangiopancreatography or magnetic resonance cholangiography in the absence of AMA.

To rule out viral infection

liver, all patients need to determine the markers of viral hepatitis.

Cholestasis caused by taking drugs or alcohol is established on the basis of anamnesis data.

The combination of diverse extrahepatic clinical manifestations (damage to the lungs, lymph nodes, bone and nervous systems, myocardium, eyes) with changes in laboratory parameters (blood calcium levels, converting enzyme activity, etc.) requires the exclusion of sarcoidosis.

Criteria for making a diagnosis of PBC:

Female gender (90% of cases);

Complaints of weakness, pruritus, jaundice;

The presence of moderate hepatomegaly of unknown origin;

Changes in the skin (hyperpigmentation, xanthelasma, traces of scratching);

Increased GGTP, alkaline phosphatase, IgM in blood serum;

Detection of AMA in blood serum;

Histological signs of PBC in the biopsy with the determination of AMA by immunohistochemical method in the liver tissue;

The presence of extrahepatic systemic manifestations.

Course and forecast

Options for the debut of the disease

An analysis of the anamnesis data and clinical symptoms of PBC patients observed by us at the TsNIIG allowed us to identify several options for the onset of the disease.

Most often, PBC debuts with pruritus (76%), much less often with jaundice (12.5%).

Much less often, the first manifestations of PBC are complications of liver cirrhosis (edematous-ascitic syndrome - 11.7%, bleeding from esophageal varices - 1.5%) and extrahepatic systemic manifestations (rheumatoid arthritis).

ritis, autoimmune thyroiditis, Raynaud's syndrome, etc.) - 1.5%.

In 7%, the disease was diagnosed at a clinically asymptomatic stage.

Options for the course of PBC

The classic clinical picture of PBC includes pruritus of varying intensity, detection of AMA in the blood serum, a slight or moderate increase in the activity of aminotransferases (2-3 times higher than normal).

In recent years, there has been a significant increase in interest in patients with PBC who do not have AMA in their blood serum, the so-called AMA-negative patients, who make up 5-15% of all patients. Some foreign scientists distinguish a group of AMA-negative patients into a separate nosological unit - autoimmune cholangitis (AIC). This pathology is characterized by all the clinical and histological signs of PBC, however, AMA are not detected in the blood serum. Some authors point to the presence of high titers of ANA and AGMA in the blood serum of such patients (1: 160 or more). There is a point of view according to which AIH is an early stage of PBC. In a comparative study of groups of patients with PBC, seronegative and seropositive for AMA, it was found that the frequency of occurrence of the DR.p1*08 and DQP*04 class II HLA genes was significantly higher in AMA-positive patients with PBC compared with the control (14.9 and 6 .5%), and in the group of AMA-negative patients, these genes were not detected. It is possible that the autoimmune response in the form of AMA formation in a certain group of patients is genetically determined.

Some patients may have clinical manifestations and/or histological features characteristic of both PBC and AIH. To describe these cases, the term "cross syndrome" (overlap-syndrome) is most often used. The frequency of this syndrome is 6-15%.

Thus, the following variants of the course of PBC can be distinguished:

1) classic AMAM2-positive;

2) AMAM2-negative;

3) cross syndrome of PBC and AIH (overlap-syndrome).

In patients with asymptomatic course of the disease, the prognosis does not differ from that in the population. The life expectancy of these patients is 15-20 years or more.

With the appearance of clinical symptoms, the prognosis worsens, the average life expectancy is about 12 years.

Various prognostic models for patients with PBC have been proposed. The most popular model developed at the Mayo Clinic, which takes into account the age of the patient, serum levels of bilirubin and albumin, pro-thrombin time, the presence or absence of ascites. In recent years, the survival rate of patients with PBC has been higher than expected by the Mayo model, which is associated with the frequent diagnosis of the disease in the early stages.

In clinical practice, to assess the prognosis, it is enough for a doctor to determine the concentration of bilirubin in the blood serum every six months. Its increase indicates the progression of the disease.

The course of PBC is continuously progressive, there is a gradual increase in jaundice and the formation of cirrhosis of the liver, followed by decompensation in the form of varicose veins of the esophagus, expansion of the portal and splenic veins, the appearance of edematous-ascitic syndrome, impaired protein-synthetic function of the liver, and an increase in hepatocellular insufficiency. The activity of cholestasis and cytolysis enzymes may decrease in the later stages of PBC due to a decrease in the functioning mass of the liver.

neither. In the terminal stage, itching may also decrease. Patients die from bleeding from varicose veins of the esophagus or with symptoms of increasing hepatocellular insufficiency.

Patients with PBC have an increased risk of developing cholangiocarcinoma and hepatocellular carcinoma and therefore should be monitored closely. Of 1692 patients with PBC seen at the Mauo clinic in 1976-1985, 114 had primary liver cancer. The risk of developing hepatocellular carcinoma in the late stages of PBC is comparable to that in hepatitis C virus-associated cirrhosis.

Pathogenetic therapy

The goal of the ongoing pathogenetic therapy in PBC is to slow down the progression of the disease, improve the quality of life and increase its duration.

Currently, the use of ursodeoxycholic acid (UDCA) is recognized as the most effective. The main effects of UDCA in the treatment of cholestatic liver diseases are due to choleretic, anti-apoptotic and immunomodulatory mechanisms. The use of the drug at a daily dose of 13-15 mg/kg for 3 months or more leads to an improvement in well-being and positive dynamics of laboratory tests in the early stages of PBC.

Summarizing the results of the treatment of PBC, LeuBsverg, and. (2001) provides data that UDCA monotherapy contributes to the normalization of biochemical parameters in 33% of patients after 3-5 years from the start of treatment. With an incomplete biochemical response, progression of the disease is noted in 28% of cases, and with a complete biochemical response - only in 5%. In patients with an incomplete biochemical response,

It is recommended to use UDCA in combination with immunosuppressants.

Data are given on a 2-year treatment of patients with PBC with a combination of UDCA and sulindac (non-steroidal anti-inflammatory drug) at a dose of 100-300 mg/day. In patients treated with sulindac, the activity of alkaline phosphatase, GGTP, as well as the content of IgM and decreased significantly compared with the UDCA monotherapy group and an incomplete biochemical response.

As a pathogenetic agent in the treatment of patients with PBC, ademetionine is also used, which increases the fluidity of cell membranes, increases their resistance to the cytotoxic effects of bile acids, free radicals and other toxic agents.

In patients with PBC and AIH overlap syndrome, glucocorticosteroids (GCS) are used in combination with UDCA - prednisolone 20-30 mg / day, followed by a decrease to a maintenance dose of 5-10 mg / day. GCS cause regression of clinical symptoms, improvement of histological and biochemical parameters, improvement of quality and increase in life expectancy. A study is underway on the simultaneous use of corticosteroids and bisphosphonates (alendronate, etidronate) in order to reduce the risk of severe osteoporosis.

Other immunosuppressive drugs.

Numerous controlled studies have shown the absence of a significant positive effect on the life expectancy of patients with azathioprine, methotrexate, cyclosporine, D-penicillamine, colchicine. At the same time, the side effects of some of them are so serious that these drugs are not currently recommended for the treatment of patients with PBC.

There is a report on the use of a new immunosuppressive drug that selectively and reversibly inhibits the function of T-lymphocytes. Reception in those

12 months of mycophenolate mofetil (2 g/day) in combination with UDCA (1 g/day) contributed to a significant decrease in the activity of alkaline phosphatase and inflammatory changes in the liver tissue. The authors suggest using this combination of drugs for long-term treatment of patients with PBC, including those at the asymptomatic stage.

As an alternative to prednisolone, which increases the manifestations of osteoporosis, data are given on the treatment of budesonide, a new generation GCS, the systemic circulation of which is 20% (prednisolone - 80%, methylprednisolone - 87%, hydrocortisone - 58%). At a daily dose of 3-9 mg/day, budesonide reduces the amount of CD3+, CD4+, CD8+ and other lymphocyte populations by 60%, which corresponds to the effectiveness of 16-32 mg/day of prednisolone. Two-year treatment with UDCA in combination with budesonide (9 mg/day) showed a significant decrease in the main parameters of cytolysis and cholestasis, as well as an improvement in the histological picture compared with UDCA alone (with a minimal risk of reducing bone mineral density).

In recent years, eosinophilic infiltration of the portal tracts in patients with PBC has played an important role. In this regard, the report on the treatment of a small group of patients with PBC with pranlukas, an antileukotriene drug used in bronchial asthma and atopic dermatitis, is topical. Positive results were obtained in all 12 patients: after 1, 2, and 6 months of treatment, the activity of AP, GGTP, and the content of IgM and IgO decreased.

Further studies are needed to evaluate the effect of all of the above drugs.

Symptomatic treatment

Symptomatic treatment for PBC is aimed at reducing pruritus,

strengthening bone tissue, eliminating the consequences of bile deficiency in the intestines.

To reduce skin itching, drugs are used that reduce the flow of bile acids into the enterohepatic circulation: ion-exchange resins (vazozan, questran, cholestyramine), other adsorbents (enterosgel, polyphepan). The use of phenobarbital (an inducer of microsomal oxidation) is limited by a pronounced sedative effect. Histamine β-receptor blockers (tavegil, diazolin, pipolfen) have a short-term effect. The use of extracorporeal methods is expanding, especially in cases of a combination of intense pruritus with hypercholesterolemia. These methods give a quick but unstable effect, their use is limited by high cost.

In the presence of osteoporosis, vitamin B3 preparations are used in combination with calcium (alfacalcidol) and other drugs.

In order to compensate for the deficiency of fat-soluble vitamins, patients are prescribed their synthetic analogues. Doses, route of administration and duration of treatment are determined individually depending on the degree of hypovitaminosis.

Liver transplant

The method of choice in the terminal stage of PBC is liver transplantation. Indications for liver transplantation in PBC (Leubiciner I., 2001):

Decreased prothrombin index below 30%;

Increasing hepatic encephalopathy;

Ascites resistant to treatment;

Reducing the volume of the liver less than 800 cm3 (according to ultrasound);

Ineffective treatment of pruritus.

Severe osteoporosis, a sharp decline in the quality of life can also serve as a basis for liver transplantation.

The immediate and long-term results of liver transplantation in patients with PBC are assessed as good. Skin itching, jaundice, ascites and manifestations of hepatic encephalopathy are rapidly reduced. Due to postoperative immunosuppressive therapy, the severity of osteoporosis initially increases, but then stabilizes. Survival of patients within 5 years after transplantation, according to large European centers, reaches 85-90%. Most patients (up to 80%) after successful liver transplantation fully restore their working capacity. In the postoperative period, 10-15% of patients showed the appearance of histological signs of PBC without clinical symptoms. The need for re-transplantation occurs in about 10% of patients.

Golovanova E.V. Diagnostic and prognostic value of antimitochondrial antibodies and cytokines in primary biliary cirrhosis: Dis. ... cand. honey. Sciences. M., 2003. 168 p.

Ivashkin V.T., Bueverov A.O. Autoimmune liver diseases in the practice of a clinician. M., 2001. 102 p.

Leishner U. A practical guide to diseases of the biliary tract: Per. with him. M., 2001. 256 p.

Podymova S.D. Modern ideas about the pathogenesis and therapy of intrahepatic cholestasis // Rus. honey. magazine 2001. T 3. No. 2. S. 66-69.

Sherlock S., Dooley J. Diseases of the liver and biliary tract: Per. from English. M., 1999. 859 p.

Yakovenko E.P., Grigoriev P.Ya., Agafonova N.A. and others. Intrahepatic cholestasis - from pathogenesis to treatment // Practitioner. 1998. No. 13. C. 20-23.

Chazouilleres O., Wendum D., Serfaty L. et al. Primary biliary cirrhosis autoimmune hepatitis overlap syndrome: clinical features and response to therapy // Hepatol. 1998. V. 28. No. 2. P. 296-301.

Faust T. W. Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation // Liver Transpl. 2001. No. 11. Suppl. 1. P 99-108.

Kim W.R., Lindor K.D., Locke G.R. et al. Epidemiology and natural history of primary biliary cirrhosis in a US community // Gastroenterol. 2000. V. 119. No. 6. P 1631-1636.

Liermann G.R.F., Evangelista G.C., McMaster P et al. Transplantation for primary biliary cirrhosis: a retrospective analysis of 400 patients in a single center // Hepatol. 2001. V. 33. No. 1. P 22-27.

Miyaguchi S., Oda M., Saito H. et al. Novel therapeutic approach to primary biliary cirrhosis patients: anti-eosinophil strategy // Hepato-Gastroenterol. 1998. V. 45. No. 23. P 1457-1461.

Nijhawan PK., Therneau T.M., Dickson E.R. et al. Incidence of cancer in primary biliary cirrhosis: The Mayo experience // Hepatol. 1999. No. 29. P. 1396-1398.

Tanaka A., Borchers A.T., Ishibashi H. et al. Genetic and family considerations of primary biliary cirrhosis // Amer. J. Gastroenterol. 2001. V. 96. No. 1. P 8-15.