As a rule, hepatitis (the ICD-10 code depends on the pathogen and is classified in the B15-B19 range), which is a polyetiologic inflammatory liver disease, has a viral origin. Today, in the structure of pathologies of this organ, viral hepatitis occupies the first place in the world. Infectionists-hepatologists treat such an ailment.

Etiology of hepatitis

The classification of the disease is complex. Hepatitis is divided into 2 large groups according to the etiological factor. These are non-viral and viral pathologies. The acute form includes several clinical variants with different causes.

In practice, the following types of non-viral ailment are distinguished:

Diseases of viral origin

At the moment, the etiology of each of these pathogens is undergoing a detailed study. In each type of ailment, genotypes were found - subspecies of viruses. Each of them always has its own distinctive features.

Viruses A and E are the least dangerous. Such infectious agents are transmitted through contaminated food and drink, and dirty hands. A month or a half is the period of cure for these types of jaundice. The most dangerous are viruses B and C. These insidious causative agents of jaundice are sexually transmitted, but more often through blood.

This leads to the development of severe (ICD-10 code B18.1). Jaundice of C viral origin (CVHC) often develops asymptomatically before the age of 15. The destructive process gradually occurs in the patient's body with chronic hepatitis C (ICD code B18.2). Unspecified hepatitis lasts at least six months.

If a pathological inflammatory process develops for more than 6 months, a chronic form of the disease is diagnosed. In this case, the clinical picture is not always pronounced. Chronic viral hepatitis occurs gradually. This form often leads to the development of liver cirrhosis if not properly treated. The described organ of the patient increases, the appearance of its soreness is observed.

The mechanism and symptoms of the development of the disease

The main multifunctional cells of the liver are hepatocytes, which play a major role in the functioning of this gland of external secretion. It is they who become the target of hepatitis viruses and are affected by the causative agents of the disease. Functional and anatomical liver damage develops. This leads to severe disorders in the patient's body.

A rapidly developing pathological process is acute hepatitis, which is in the international classification of diseases of the tenth revision under the following codes:

• acute form A - B15;
• acute form B - B16;
• acute form C - B17.1;
• acute form E - B17.2.

The blood test is characterized by high numbers of liver enzymes, bilirubin. In short periods of time, jaundice appears, the patient has signs of intoxication of the body. The disease ends with recovery or chronicity of the process.

Clinical manifestations of the acute form of the disease:

Danger of viral jaundice

Of all the pathologies of the hepatobiliary system, the viral type of the disease most often leads to the development of cancer or cirrhosis of the liver.

Due to the risk of the formation of the latter, hepatitis is especially dangerous. The treatment of these pathologies is extremely difficult. Fatal outcome in the case of viral hepatitis is often observed.

Diagnostic tests

Establishing the causative agent of the pathology, identifying the cause of the development of the disease are the purpose of the examination.

Diagnostics includes the following list of procedures:

1. Morphological studies. Puncture biopsy. A thin hollow needle is used to puncture the tissue for the purpose of examining biopsies.
2. Instrumental tests: MRI, ultrasound, CT. Laboratory tests: serological tests, liver function tests.

Therapeutic methods of exposure

Specialists, based on the results of the diagnostic examination, prescribe conservative treatment. Specific etiological therapy is aimed at eliminating the causes of the disease. In order to neutralize toxic substances, detoxification is mandatory.

Antihistamines are indicated for various types of ailment. Diet therapy is required. A balanced, sparing diet is essential for hepatitis.

At the first signs of trouble, it is important to contact an experienced specialist in a timely manner.

Chronic hepatitis C is a serious inflammatory liver disease that affects the tissues of an organ and, if untreated, leads to its complete destruction. The HCV virus provokes the pathology. This form is recognized as the most dangerous among hepatitis, which is due to the high risk of cirrhosis and oncological neoplasms, as well as the severe course of the disease.

Chronic hepatitis C, ICD-10 code B15-B19, is one of the six most common ailments around the world. In addition, the disease has very blurred symptoms. This leads to a high rate of development of serious complications due to delayed treatment.

Symptoms

The manifestation of the initial signs of hepatitis depends on the individual characteristics of the human body. The period between the penetration of the virus into the bloodstream and the appearance of the first symptoms, on average, ranges from several weeks to six months. These signs include:

• fatigue;
• decreased concentration of attention, performance;
• constant feeling of tiredness.

At the subsequent stages of disease progression, the following are observed:

• loss of appetite, regular nausea and vomiting with bloody discharge;
• drastic weight loss;
• yellowing of the skin, as well as redness of the palms and feet, the presence of itching.

Patients also note joint pain and sudden weight loss up to anorexia. In addition, the size of the liver and spleen increases. There is a general deterioration in the patient's condition, weakness and apathy.

Causes

The provocateur of the development of hepatitis C is the HCV virus, which enters the human body through blood or other biological fluids. The infection remains active for several days even after the material has dried. The disease enters the chronic phase due to its untimely detection. This is due to the complexity of diagnosis and the absence of symptoms at the initial stages of the development of pathology. Also, a similar situation can occur due to the patient's negligent attitude to his own health, which consists in ignoring medical recommendations, having bad habits, refusing to take medicines and following a special diet.

Infection routes

You can get viral hepatitis C in the following ways:

1. Medical and non-medical manipulations: dental services, injections, tattoos, piercings, manicure procedures using unsterilized instruments, blood and plasma transfusions, organ and tissue transplants from an infected donor.
2. Sexual contact with a person infected with hepatitis C.
3. Operations, childbirth in non-sterile conditions.
4. Using household items of a person infected with hepatitis C: razors, toothbrushes, and so on.

It is possible to suppress the activity of the virus by applying disinfectants with chlorine to the required surfaces.

Most susceptible to infection with hepatitis C:

• workers of medical and epidemiological institutions;
• persons who regularly use intravenous drugs;
• people leading a promiscuous intimate life, manifested in a large number of unprotected sex with questionable partners.

Viral hepatitis C is not transmitted by airborne droplets, through touch and household contacts.

Diagnostics

Detection of hepatitis C contains a set of measures, including instrumental diagnostics. This list includes:

1. Delivery of the necessary blood tests. First of all, this is a biochemical study. Based on it, the attending physician makes the first conclusions and prescribes subsequent diagnostic measures.
2. Analysis for the presence of antibodies to the disease virus.
3. Ultrasound examinations of the liver and other abdominal organs.
4. Tests to determine the genotype of the HCV virus, which allows you to draw up an optimal treatment plan.
5. Liver biopsy.
6. Fibrotest.
7. Computer and magnetic resonance imaging and radioisotope research methods.

It is necessary to start diagnostics at the first suspicion of the presence of viral hepatitis C in the body. Even a slight delay can lead to dire irreversible consequences. Operational actions ensure the elimination of the development of complications.

How to treat

The therapeutic course for combating hepatitis C is a list of procedures that can suppress the activity of the virus, eliminate the development of complications and improve the patient's quality of life. Treatment includes:

1. Medication component: the use of prescribed drugs in the appropriate dosage.
2. Compliance with a special diet with restriction of proteins, fats and carbohydrates; drinking regimen.
3. Refusal from addictions: the use of alcoholic and narcotic drugs, smoking tobacco.
4. Physiotherapy procedures.
5. Physiotherapy.
6. Compliance with sleep patterns.
7. General strengthening of the body and increasing immunity: taking vitamin-mineral complexes and so on.
8. Limiting contact with other viral diseases.
9. Providing emotional comfort to the patient.

Taken together, compliance with these conditions gives high rates of recovery for patients around the world.

Liver transplantation is sometimes done. However, the need for such a cardinal method is quite rare, especially since it has a number of serious contraindications.

Forecast

The expected results of hepatitis C treatment are based on the stage of the disease at the time of initiation of therapy, the presence of concomitant ailments and complications. The patient's diligence and patience, as well as the high qualifications of the hepatologist, are important factors.

Doctors give a favorable prognosis if the fight against the disease began in the initial phases, when the chronic course of hepatitis C with serious damage to the liver and the body as a whole is not yet observed.

The key condition is strict adherence to all medical recommendations and the prescribed therapeutic course, taking the necessary medications. At the current stage of development of medicine and special equipment, the percentage of recovery from viral hepatitis C is 45-90%.

Prevention

There is currently no vaccination against hepatitis C. However, despite this, serious illness can be avoided. It is enough to monitor the state of your own body and observe preventive measures. These include:

1. Systematic strengthening of immunity through sports, taking vitamins and minerals.
2. Compliance with the rules of personal hygiene.
3. Protected sexual intercourse with a regular partner.
4. Carrying out medical and non-medical procedures in proven clinics with qualified specialists.
5. Regular tests for the presence of viral hepatitis C in the body.
6. Compliance with the rules of a healthy lifestyle.
7. A balanced diet.
8. Stable psycho-emotional state.

Approximately 20% of cases of hepatitis C infection are of unclear etiology. Sometimes the disease occurs even in those population groups that lead a healthy lifestyle and are attentive to their own body. It is important to remember that prevention is a serious set of measures aimed at preventing the occurrence of an illness, which must be adhered to even in the absence of an obvious danger of infection.

Chronic viral hepatitis C ICD-10 code - B15-B19. Today this disease is recognized as curable. Complex therapy gives tremendous results. The course of treatment must be accompanied by the rejection of alcohol, drugs and tobacco products. Physical therapy and exercise are of great importance.

Gilbert's Syndrome

ICD-10 code

E80.4. Gilbert's syndrome.

Gilbert's syndrome is pigmentary hepatosis (simple familial cholemia, constitutional hyperbilirubinemia, idiopathic unconjugated hyperbilirubinemia, non-hemolytic familial jaundice) with an autosomal dominant mode of inheritance, characterized by a moderate intermittent increase in the content of unbound (indirect) bilirubin in the blood. The syndrome was first described by the French doctors A.N. Gilbert and P. Lereboullet in 1901.

This is the most common form of hepatitis pigmented hepatosis, which occurs in 2-5% of the population. Among Caucasians, the prevalence of the syndrome is 2-5%, among Mongoloids - 3%, among Negroids - 36%. The disease manifests itself in adolescence and continues almost throughout life. It is more common in males.

Etiology and pathogenesis

The syndrome is caused by a mutation in a gene UGT1A1,which encodes the enzyme uridine diphosphate glucuronyl transferase (UDPGT). The following links lie in the pathogenesis of the syndrome:

Violation of the capture of bilirubin by microsomes of the vascular pole of hepatocytes;

Disruption of bilirubin transport by glutathione-8-transferase, which delivers unconjugated bilirubin to hepatocyte microsomes;

Inadequacy of the microsomal enzyme UDFGT, with the help of which bilirubin is conjugated with glucuronic and other acids.

In Gilbert's syndrome, the activity of UDFGT decreases by only 10-30% compared to the norm, the main importance is attached to the violation of the capture of bilirubin by hepatocytes, which is associated with an abnormality of membrane permeability and a defect in the protein of intracellular transport.

Bilirubin exchangeconsists of its transport in blood plasma, capture by the liver, conjugation, biliary excretion (Fig. 6-1).

Every day, the human body produces about 250-300 mg of unconjugated bilirubin: 70-80% of this amount is the result of the daily breakdown of erythrocyte hemoglobin; 20-30% is formed from heme proteins in the bone marrow or liver. For a day, in a healthy person, about 1% of circulating erythrocytes disintegrates.

Bilirubin, which is formed in the cells of the reticuloendothelium, is a toxic compound. It is called unconjugated, indirect, or free, unbound bilirubin (due to the specificity of the reaction in its determination), is water-insoluble. That is why it is present in blood plasma in the form of a compound with albumin. The albumin-bilirubin complex prevents bilirubin from entering the urine through the glomerular membrane.

With the blood flow, indirect bilirubin enters the liver, where this form of bilirubin is converted into a less toxic form - direct (bound, conjugated) bilirubin. Both fractions make up total bilirubin.

In the liver, unconjugated bilirubin is separated from albumin at the level of microvilli of hepato-

Figure: 6-1.Exchange and conjugation of bilirubin

cytes, its capture by intrahepatic protein. The conjugation of bilirubin with the formation of mono- and diglucuronides (conjugated bilirubin) is provided by UDFGT.

The release of bilirubin into bile is the final stage of pigment exchange and occurs through the cytoplasmic membranes of hepatocytes.

In bile, conjugated bilirubin forms a macromolecular complex with cholesterol, phospholipids, and bile salts. Then, with bile, it enters the duodenum and small intestine, where it is transformed into urobilinogen, part of which is absorbed through the intestinal wall, enters the portal vein and is transported with blood flow to the liver (intestinal-hepatic circulation), where it is completely destroyed.

The main amount of urobilinogen from the small intestine enters the large intestine, where it is converted into stercobilinogen by bacteria and is excreted in the feces. The amount of fecal stercobilinogen and stercobilin varies from 47 to 276 mg / day, depending on body weight and gender.

Less than 2% of bilirubin is excreted in the urine as urobilin.

Clinical picture

Light yellowness, including icterus of the sclera, is the main symptom of the disease. In some cases, the staining of the skin occurs (Fig. 6-2, a), especially the feet, palms, nasolabial triangle, and armpits.

Figure: 6-2.Gilbert's syndrome: a - a patient - a participant in a beauty contest; b - ultrasound: no changes; c - a macropreparation of the liver with accumulation of lipofuscin

Patients should be examined in daylight. Under electric lighting, skin color is distorted and can be misinterpreted.

The yellowness of the skin and visible mucous membranes becomes clearly visible when the level of bilirubin in the blood serum reaches 43-50 μmol / L and higher.

Jaundice and hyperbilirubinemia are intermittent, so these symptoms are rarely permanent. Stress (for example, during exams or during a lot of physical exertion that occurs when lifting weights) contributes to the appearance of jaundice and increased icterus of the sclera. Various operations, colds, improper diet, fasting, drinking alcohol and some types of drugs contribute to the intensification of symptoms. Total bilirubin in Gilbert's syndrome ranges from 21 to 51 μmol / L and periodically rises to 85-140 μmol / L.

In half of the cases, dyspeptic complaints are observed: flatulence, stool disturbance, nausea, belching, lack of appetite. The onset of jaundice can be accompanied by discomfort in the liver and weakness.

The syndrome is associated with connective tissue dysplasia (especially often similar to the Marfan and Ehlers-Danlos syndromes).

Diagnostics

Diagnosing a disease involves testing.

Serum bilirubin test,which rises against the background of starvation. The patient receives food for 2 days, the energy value of which does not exceed 400 kcal / day. The level of bilirubin in blood serum is determined on an empty stomach and after 48 hours. The sample is positive if its rise is

50-100%.

Phenobarbital test- the level of bilirubin decreases while taking phenobarbital due to the induction of conjugated liver enzymes.

Nicotinic acid test- intravenous administration of the drug causes an increase in the level of bilirubin due to a decrease in the osmotic resistance of erythrocytes.

The result of a stool test for stercobilin is usually negative.

Liver tests, in particular the levels of the enzymes AST, ALT, ALP, etc., as a rule, are within normal limits or slightly increased. An increase in total protein and dysproteinemia may be observed; prothrombin time - within normal limits. There are no markers of hepatitis B, C, D viruses.

Molecular diagnostics include DNA analysis of the UDFGT gene.

With the help of ultrasound of the abdominal organs, the size and condition of the liver parenchyma are determined (Fig. 6-2, b); size, shape, wall thickness, possible calculi in the gallbladder and bile ducts.

If there are indications for the exclusion of chronic hepatitis (CG), liver cirrhosis, a percutaneous puncture biopsy of the liver with a morphological assessment of the biopsy is performed.

Pathomorphology

Morphological changes in the liver are characterized by fatty degeneration of hepatocytes and the accumulation of yellowish-brown lipofuscin pigment in them, more often in the center of the lobules along the bile capillaries (Fig. 6-2, c).

Differential diagnosis

Differential diagnosis is carried out with all types of hyperbilirubinemia (Table 6-1), hemolytic anemias, congenital cirrhosis of the liver and hepatitis, atresia of the biliary tract or small intestine, etc.

Table 6-1.Differential diagnosis of hereditary hepatosis

Treatment

Patients, as a rule, do not need special treatment, since Gilbert's syndrome is not a disease, but an individual, genetically determined feature of the body. Observance of the regime of study, work, rest, nutrition is of fundamental importance.

Alcoholic beverages and fatty foods are highly undesirable, physical overload (professional sports), sun exposure, long breaks between meals, and fluid restriction are not recommended.

Components of therapy and prevention of exacerbations of Gilbert's syndrome:

Diet therapy;

Elimination of provoking factors (infections, physical and mental stress, the use of hepatotoxic drugs and alcohol);

Contraindication to insolation.

An episode of jaundice can resolve on its own, without the use of drugs.

If the bilirubin level reaches 50 μmol / l and is accompanied by poor health, phenobarbital can be taken in a short course (1.5-2.0 mg / kg, or 30-200 mg / day in 2 doses for 2-4 weeks). Phenobarbital (luminal *) is part of such drugs as corvalol *, barboval *, valocordin *, therefore sometimes they prefer to use these drugs (20-30-40 drops 3 times a day for 1 week),

although the effect of such treatment is observed in only a small proportion of patients. The inducers of enzymes of the monoxidase system of hepatocytes, in addition to phenobarbital, include zixorin (flumecinol *), prescribed to adolescents at a dose of 0.4-0.6 g (4-6 capsules) once a week or 0.1 g three times a day in within 2-4 weeks. Under the influence of these drugs, the level of bilirubin in the blood decreases, dyspeptic symptoms disappear, but in the course of treatment, lethargy, drowsiness, and ataxia occur. In such cases, these drugs are prescribed in minimal doses before bedtime, which allows them to be taken for a long time.

Due to the fact that a significant part of patients develop cholecystitis and gallstone disease, it is recommended to take infusions of choleretic herbs, periodic tubing of sorbitol (xylitol), Karlovy Vary salt, etc. Hepatoprotectors are shown: ursodeoxycholic acid preparations (ursosan *, ursofalk *), phospholipids (Essentiale *), Silibinin (Carsil *), Milk Thistle Fruit Extract (Legalon 70 *), Field Artichoke Leaf Extract (Hofitol *), Liv 52 *; choleretics: cholagol *, cholenzyme *, allochol *, berberine *, holosas *; vitamin therapy, especially B vitamins.

The elimination of conjugated bilirubin is possible with the help of enhanced diuresis, the use of activated carbon, which adsorbs bilirubin in the intestine.

Thermal physiotherapy for the liver area is contraindicated.

Through phototherapy, the destruction of bilirubin fixed in tissues is achieved, thereby releasing peripheral receptors that can bind new portions of bilirubin, preventing its penetration through the blood-brain barrier.

Prevention

Prevention includes adherence to work, nutrition, rest. Avoid significant physical exertion, fluid restriction, fasting and hyperinsolation. The use of alcoholic beverages, hepatotoxic drugs is unacceptable.

Gilbert's syndrome is not a reason to refuse vaccinations.

Reorganization of chronic foci of infection and treatment of the existing pathology of the biliary tract are mandatory.

Forecast

The forecast is favorable. Hyperbilirubinemia persists for life, but is not accompanied by progressive changes in the liver and increased mortality. In life insurance, such people are classified as normal risk. When treated with phenobarbital, the bilirubin level decreases to normal values. The development of inflammation in the biliary tract, gallstone disease, psychosomatic disorders is possible.

Parents of children with this syndrome should consult a geneticist before planning another pregnancy.

The same should be done if relatives of a married couple planning to have children are diagnosed with this syndrome.

FATTY LIVER DEGENERATION

ICD-10 code

K76.0. Fatty degeneration of the liver.

Hepatosis (hepatic steatosis, non-alcoholic steatohepatitis) is a group of liver diseases, which are based on metabolic disorders in hepatocytes and the development of dystrophic changes in liver cells, while inflammatory phenomena are absent or mild.

In recent years, there has been a significant increase in the incidence of fatty liver degeneration, mainly associated with an increase in the prevalence of obesity. Among patients who underwent liver biopsy, approximately 7-9% of cases of hepatosis in Western countries and 1-2% in Japan are detected.

Etiology and pathogenesis

The causes of the disease are considered obesity, diabetes mellitus, dyslipidemia, rapid weight loss, lack of protein in the diet, congenital defects in β-oxidation of fatty acids, α-1-antitrypsin deficiency, exposure to liver toxic substances, including alcohol, etc. Hepatosis can be both an independent disease and a manifestation of other diseases.

Excessive fat accumulation in liver tissue (in hepatocytes and Ito cells) may result from first impact(Fig. 6-3, a, d) - saturated with lipids, simple carbohydrates and high calorie food:

Increasing the supply of free fatty acids to the liver;

Reducing the rate of β-oxidation of free fatty acids in the liver mitochondria;

Increased synthesis of fatty acids in liver mitochondria;

Reducing the synthesis or secretion of very low density lipoproteins and the export of triglycerides in their composition.

The result of a violation of the diet is insulin resistance and fatty liver.

Second impact(see Fig. 6-3, d) implies a violation of the excretion of lipids from the liver, which occurs when the amount of substances involved in their processing (protein, lipotropic factors) decreases. The formation of phospholipids, β-lipoproteins, lecithin from fats is impaired. In the pathogenesis, tumor necrosis factor-α, endotoxin, immune factors are important. It is assumed that, regardless of the reasons for the development of steatosis, the basis of inflammatory-necrotic changes in the liver are universal mechanisms. Being highly reactive compounds, free fatty acids serve as a substrate for lipid peroxidation. The generated free radicals cause the destruction of lipid, protein components of membranes, liver receptors, etc., causing further changes in the liver.

Classification

Distinguish between pigmentary and fatty hepatosis. Most often, the term "hepatosis" means fatty hepatosis (steatosis), since pigmentary hepatosis occurs much less frequently and is considered separately (see "Rare syndromes"), with the exception of Gilbert's syndrome.

Clinical presentation and diagnosis

In the initial stages, symptoms are minimal. As a rule, the course of the disease is latent, only an increase in the activity of hepatic transaminases and hepatomegaly are noted. In many patients, liver dysfunctions are diagnosed by chance, during examination for other diseases. There is a minimal or moderately pronounced activity of inflammation in the liver, detected by biochemical studies of blood serum. However, without treatment, a transition to cirrhosis of the liver can be observed, the phenomena of liver failure gradually increase.

Fatty hepatosis is often concluded by doctors of ultrasound diagnostics on the basis of characteristic signs: a uniform increase in the liver, a diffuse increase in its echogenicity (sometimes pronounced) while maintaining its uniformity, although with the progression of the process, a characteristic granularity of the parenchyma appears, indicating the onset of the development of steatohepatitis and hepatitis (Fig. 6-3, b).

Pathomorphology

According to morphological studies, steatohepatitis is an excessive accumulation of triglycerides in the liver, which is accompanied by damage to cell membranes and other organelles of hepatocytes, inflammatory process, fibrosis up to liver cirrhosis (Fig. 6-3, c).

Figure: 6-3.Functions and diseases of the liver: a - participation of the liver in lipid metabolism; b - ultrasound: hepatomegaly and increased liver echogenicity; c - macrodrug: liver steatosis; d - staged formation of liver pathology

Treatment

Diet therapy is a permanent and safe method of treating fatty liver disease.

In order to normalize the oxidation of fatty acids in mitochondria, improve the transport of triglycerides from the liver, and reduce the processes of lipid peroxidation, drugs are prescribed that improve lipid metabolism - hepatoprotectors, vitamin B 12, folic acid, thioctic acid (lipoic acid *), etc.

Prevention

A healthy lifestyle and a healthy diet are the foundation of primary prevention (Figure 6-4). Adequate physical activity is recommended.

Figure: 6-4.Nutritional pyramid for fatty liver degeneration

Dispensary observation is described below (see "Prevention of chronic hepatitis").

Forecast

With the exclusion of causal factors and timely treatment, recovery is possible, however, hepatosis can transform into chronic hepatitis and cirrhosis (see Fig. 6-3, d).

CHRONIC HEPATITIS

ICD-10 code

K73. Chronic hepatitis.

Chronic hepatitis is a group of diseases accompanied by the development of a diffuse inflammatory process in the liver, lasting more than 6 months, confirmed by biochemical parameters, the results of a morphological examination of the liver, as well as specific markers in the blood serum.

The prevalence of hCG has not been precisely established due to the large number of erased and asymptomatic forms, the lack of population studies. Chronic viral hepatitis (CVH) caused by persistence of hepatitis B (29.2%), C (33.3%), chronic hepatitis B + C (16.7%), less often B + D (4.1 %), D + G (no more than 2%). In 16.7% of cases, hepatitis of unknown etiology is detected.

Classification

The modern classification of hepatitis is presented in table. 6-2. Taking into account the etiology, the following types of hepatitis are distinguished.

. Specific viral hepatitis.The main forms of such hepatitis are hepatitis A, B and C. Hepatitis D is less common in the world. Hepatitis E remains a major problem in developing countries. Other hepatitis viruses (G, TTV, etc.) have been described, but their clinical significance is not great.

. Nonspecific viral hepatitisare caused by a group of viruses that can infect the liver and other organs. For example, the virus of infectious mononucleosis (Epstein-Barr virus) selectively affects the cells of the reticuloendothelial system (clinically manifested in the form of tonsillitis, hypersplenism, hepatitis, etc.). Adenovirus causes pharyngoconjunctival fever, acute pneumonia, hepatitis. Herpes simplex virus is an AIDS indicator infection.

Hepatitis - manifestation of an etiologically independent disease(with leptospirosis, pseudotuberculosis).

Hepatitis associated with the use of drugs - toxic-allergicand medicinal hepatitis.Alcoholic hepatitis is a combined lesion with acetaldehyde and some other factor.

. Nonspecific reactive hepatitis- the reaction of liver cells to the pathology of neighboring organs: pancreas, gallbladder, duodenum. Reactive hepatitis develops in patients with chronic pancreatitis, duodenal ulcer.

Among autoimmune forms of chronic hepatitis3 types of diseases have been identified (see Table 6-2).

Row rare liver diseasesmay have clinical and histological features of chronic persistent hepatitis:

Primary biliary cirrhosis;

Wilson-Konovalov's disease;

Primary sclerosing cholangitis;

Lack of α-1-antitrypsin.

The stage of fibrosis is established on the basis of a pathomorphological examination of liver biopsies (Table 6-3), roughly - according to ultrasound data (Table 6-4).

Table 6-2.Classification of Chronic Hepatitis (International Expert Group, Los Angeles, 1994)

* Established according to the results of histological examination of liver tissue and tentatively - according to the degree of ALT and AST activity (1.5-2 norms - minimal, 2-5 norms - low, 5-10 norms - moderate, above 10 norms - pronounced). ** Established on the basis of morphological examination of the liver and approximately - according to ultrasound data.

Table 6-3.Index of histological activity of hepatitis in points (Knodell R..J. Et al.,1994)

Note:1-3 points - the minimum degree of activity of chronic hepatitis; 4-8 - chronic hepatitis of moderate severity; 9-12 points - moderate chronic hepatitis; 13-18 points - severe chronic hepatitis.

Table 6-4.Ultrasound criteria for the stages of liver fibrosis in chronic hepatitis in children

Mixed hepatitisestablished as the main diagnosis in the presence of simultaneous replication of 2 types of virus or more. With the replication of one and the integration of the other, the main hepatitis and concomitant are established.

Chronic viral hepatitis

ICD-10 codes

B18. Chronic viral hepatitis.

818.0. Chronic viral hepatitis B with D-agent.

818.1. Chronic viral hepatitis B without D-agent.

818.2. Viral hepatitis C is chronic.

818.8. Other chronic viral hepatitis.

818.9. Unspecified chronic viral hepatitis.In more than 70% of cases, the cause of the development of chronic hepatitis is hepatotropic viruses B, C and D. There are 350-400 million people infected with the hepatitis B virus in the world, and about 1 million people die annually from diseases associated with hepatitis B virus (HBV) infection ... The prevalence of HBV infection in different countries ranges from 0.1 to 20%. The risk of acute HBV infection becoming chronic with age decreases: with perinatal infection it reaches 90%, with infection at the age of 1-5 years - 25-35%, and with infection of adults - less than 10%.

Etiology and pathogenesis

The mechanism of formation, diagnosis of hepatitis B and C are shown in Fig. 6-5. Viral hepatitis B (8 main genotypes - A-H) is found in blood and other biological fluids (semen, saliva, nasopharyngeal mucus), transmitted in four main ways:

Sexual;

Perinatal (from mother to child in the prenatal period and in childbirth);

Parenteral (through blood);

Horizontal (with close household contact or through infected common objects; mainly observed in early childhood).

In children, the main route of transmission of viral hepatitis B is perinatal. If a pregnant woman is a carrier of hepatitis B virus (and, in addition, is HBeAg-positive), the probability of infection of the newborn with the development of a carrier of the virus is 90%. As adults, 25% of these children die from chronic liver failure or liver cancer. Although HBsAg, HBeAg, and hepatitis B virus DNA are found in breast milk, the type of feeding does not affect the risk of hepatitis B virus transmission. Other risk factors for hepatitis B infection include:

Transfusion of blood and / or its components;

Injection of drugs, tattoos, piercings and other invasive procedures on the skin;

Unprotected penetrating sex, especially anal and vaginal intercourse;

Organ transplant;

Work in medical institutions;

Hemodialysis.

In regions with low endemicity of HBV infection, adolescents and young people have the highest incidence. The most common routes of transmission of viral hepatitis B in these groups are sexual and parenteral (with unsafe drug injections, in particular, the repeated use of disposable syringes).

It is considered that chronic hepatitis B(CHB) is a disease that is primarily chronic or occurs after an erased or subclinical form of acute infection.

CHB phases:

Initial, or immune tolerance;

Immune response (replicative), proceeding with pronounced clinical and laboratory activity;

Integrative;

Carriage of HBsAg.

The hepatitis B DNA virus (HBV DNA) itself does not cause cytolysis. Damage to hepatocytes is associated with immune responses in response to circulating viral and hepatic antigens. In the 2nd phase of viral replication, viral antigens are expressed: HBsAg (surface), HBcAg, (nuclear), HBeAg (Fig. 6-5, a), the immune response is more pronounced, which causes massive necrosis of the liver parenchyma and further mutation of the virus.

Replication of the hepatitis B virus is also possible outside the liver - in bone marrow cells, mononuclear cells, thyroid and salivary glands, which causes extrahepatic manifestations of the disease.

Transmission routes chronic hepatitis C(CHC) are similar to those with CHB. Unlike viral hepatitis B, the hepatitis C RNA virus has a direct hepatotoxic effect. As a consequence, the replication of the virus and its persistence in the body are associated with the activity and progression of hepatitis. It is interesting that viral hepatitis C is able to block apoptosis (programmed death) of cells affected by it in order to stay in the human body for a long time. Apoptosis is a normal process that rid the body of “worn out” or diseased cells. A protein encoded in the genome of hepatitis C virus, known as NS5A, blocks the opening of potassium channels in liver cells, protecting their "shelters" from natural death and thus staying in the human body for a long time. The life cycle of viral hepatitis C is shown in Fig. 6-5, b.

Figure: 6-5.Chronic hepatitis C and B: a - diagnosis of hepatitis C and B and dynamics of serological markers of hepatitis B; b - life cycle of the hepatitis C virus

Causative agent chronic hepatitis D(HGO) - RNA-containing particle, the outer shell of which is represented by HBsAg. In the center of the particle is the antigen of the hepatitis D virus. The delta virus is able to multiply in liver cells only in the presence of viral hepatitis B, since its proteins are used to exit the cell of the delta virus particle. The disease proceeds simultaneously with viral hepatitis B in the form of a coinfection or superinfection.

Clinical picture

The clinical picture of hCG is weak and nonspecific. Asymptomatic course is observed in 25% of patients. The formation of chronic hepatitis occurs more often in the outcome of acute hepatitis, proceeding in the form of atypical (erased, anicteric, subclinical) forms and extremely rarely - with manifest (icteric) forms of acute hepatitis. The acute phase of hepatitis and the appearance of clinical symptoms of the chronic form of the disease are separated by 5 years or more.

The clinical manifestations of hCG depend on the child's age at the time of infection, the severity of morphological

changes in the liver, phases of the infectious process (replication, integration), premorbid background. In children, unlike adults, cholestatic variantHCG is rare; in the presence of cholestasis, it is necessary to exclude congenital pathology of the intra or extrahepatic passages, α-1-antitrypsin deficiency, cystic fibrosis. The main syndromes of the disease are shown in table. 6-5.

Table 6-5.The main syndromes of chronic viral hepatitis

Extrahepatic manifestationsassociated with extrahepatic replication of the virus, are more characteristic of CHC, may manifest as recurrent dermatitis, hemorrhagic vasculitis, glomerulonephritis, arthropathies, thyroiditis, Sjogren's syndrome, pancreatopathies. Extrahepatic manifestations often develop at puberty, girls are characterized by the development of endocrine disorders, and boys develop glomerulonephritis and other diseases.

Extrahepatic manifestations include vascular changes (Table 6-6; Fig. 6-6). In children, they are much less common; their presence obliges an extended study of liver function.

Table 6-6.Vascular extrahepatic manifestations in chronic hepatitis

Figure: 6-6.Vascular extrahepatic manifestations in chronic hepatitis: a - telangiectasia; b - capillary; c - palmar erythema

Diagnostics

Specific methods. With the help of enzyme-linked immunosorbent assay (ELISA), the main markers of hCG are detected, with the help of polymerase chain reaction (PCR) - DNA or RNA virus (Table 6-7; Fig. 6-5, a).

Table 6-7.Marker diagnostics of chronic hepatitis B and C

Serological markersviral hepatitis B is used to establish the diagnosis and stage of the disease.

Antigens were presented above (see Fig. 6-5, a). Antibodies to the surface antigen of the virus (anti-HBsAg) appear in the blood after 3-6 months and persist for many years or possibly for life. Their detection indicates either a previous infection or previous vaccination.

Nuclear antigen (HBcAg) in the blood usually does not circulate, however, antibodies to it appear in the early stages of the disease, their titer quickly reaches a maximum, and then gradually decreases (but does not completely disappear). First, antibodies of the IgM class appear (anti-HBcAg IgM), then IgG appears. Antigen E (HBeAg) appears in the blood for a short time at the onset of the disease, which is accompanied by the production of antibodies to it (anti-HBe).

Chronic CHB infection is characterized by the presence of HBsAg and anti-HBcAg IgG in the blood.

In CHC, in addition to viremia (HCV RNA), antibodies of the IgM and IgG classes are detected. Without exacerbation of RNA, CHC and anti-HCV IgM are not detected, but antibodies of the IgG class remain (see Tables 6-7).

TO non-specific methodsinclude biochemical, immunological tests and instrumental studies.

Biochemical testsdo not carry information about the etiology of the disease, but reflect the nature of liver damage and the state of its function. These include:

An increase in the level of liver enzymes: in chronic hepatitis, an increase in ALT is more pronounced than AST, which is associated with different localization of enzymes (ALT - in the cytoplasm, AST - in mitochondria), in cirrhosis, on the contrary, the activity of AST prevails over that of ALT; also characterized by an increase in such enzymes as lactate dehydrogenase, γ-glutamyl transpeptidase,

ALF;

Violation of fat and pigment metabolism: an increase in the direct fraction of bilirubin, the content of total cholesterol, β-lipoproteins, ALP activity, 5-nucleotidase;

Violation of the protein-synthetic function of the liver: a decrease in total protein, an increase in the thymol test, a decrease in sublimate test, a decrease in the level of prothrombin, persistent dysproteinemia due to an increase in globulin fractions, especially γ-globulins, and a decrease in albumin.

Biochemical syndromes reflecting liver dysfunctions are presented in Chapter 1 (see Table 1-8, changes in protein fractions - Fig. 1-16, b).

Immunological tests.Characterized by a decrease in the levels of T-suppressors, an increase in the levels of serum immunoglobulins.

Instrumental methods.Ultrasound of the liver is an obligatory research method for chronic hepatitis, as it allows visualizing the liver, determining its size, revealing liver cirrhosis and portal hypertension. Even with an asymptomatic course of the disease, this method can reveal an increase in the liver, a change in the echogenicity of the parenchyma. Reohepatography, puncture biopsy of the liver can be used.

Today liver biopsyis the gold standard for the diagnosis of liver diseases (Fig. 6-7, a). During the biopsy, a piece of liver with a diameter of about 1 mm is obtained using a special needle. The procedure is carried out under local or general anesthesia and under ultrasound control, since it is necessary to control the needle movement, which makes the manipulation safe.

The degree of hCG activity is most often assessed using a semi-quantitative histological activity index, also known as the Knodell system, determined in points (see Table 6-3). The histology of a biopsy (tissue sample) of the liver makes it possible to decide on the need and tactics of antiviral therapy.

Pathomorphology

Morphological examination of liver biopsy specimens already in the first months of a child's life with primary chronic hepatitis reveals signs of inflammation that persist for many years, as well as progressive fibrosis with the formation of liver cirrhosis.

Figure: 6-7.Diagnostics of chronic hepatitis: a - biopsy technique; histological picture: b - CHB (staining with hematoxylineosin; χ 400); c - CHC (x 400).

CHB is characterized by necrosis (Fig. 6-7, b); pathognomonic sign in CHC is vacuolization of hepatocyte nuclei, the so-called opaque-glassy hepatocytes, as well as their stepwise necrosis (Fig. 6-7, c).

Differential diagnosis

Treatment

IN replication phase (exacerbation)shows hospitalization in a specialized department, bed rest, strict diet therapy.

Basic therapyincludes appointment antiviral drugs.Indications for its appointment:

The presence of markers of active hepatitis replication;

ALT levels are more than 2-3 times higher than normal;

Absence of cholestasis and signs of liver cirrhosis with decompensation;

Absence of severe concomitant diseases in the stage of decompensation;

Absence of autoimmune diseases, immunodeficiency state, mixed hepatitis.

Interferon inducersare characterized by low toxicity and the absence of side effects, unlike interferon preparations, thanks to their use, it is possible to significantly increase the life expectancy in children and adults (Fig. 6-8).

Figure: 6-8.Chronic hepatitis (course and treatment): a - antiviral treatment of children and adults with chronic viral hepatitis B and C and the years of life gained; b - natural course of hepatitis B

Interferon preparationscontraindicated in psychosis, epidemic syndrome, severe neutro- and thrombocytopenia, autoimmune diseases (AIH, thyroiditis, etc.), decompensated liver cirrhosis and kidney disease, heart pathology in the stage of decompensation.

Interferon-a-2b (reaferon *, roferon *, neuroferon *) - lyophilisate for preparation of a suspension for oral administration - is prescribed 30 minutes before meals, 1-2 ml of chilled boiled water are added to the contents of the bottle before use. The drug in injections is injected with CHB at a dose of 5 million IU / m 2, with CHC - 3 million IU / m 2 body surface area three times a week (1 time with an interval of 72 hours) s / c or i / m. The calculated dose of interferon is initially administered within 3 months. After this period, a control study is carried out (RNA or DNA of the virus, activity). If there is no clear positive dynamics of these indicators (the disappearance of RNA, virus DNA from the blood, a decrease in ALT), it is better to stop treatment according to this scheme or switch to combination therapy. But if there is a decrease in ALT activity, a decrease in the concentration of RNA, DNA of the virus in the blood, treatment according to the chosen scheme is continued for another 3 months, followed by a control

laboratory research. With positive dynamics in CHC, treatment is continued for 3 months to consolidate the results of treatment. Thus, the course of treatment for CHB is 6 months, for CHC - 9-12 months.

In pediatric practice, Viferon is used (a combination of α-interferon with membrane stabilizers), which is produced in rectal suppositories. Doses for children: up to 3 years old - 1 million IU, over 3 years old - 2 million IU 2 times a day with an interval of 12 hours 3 times a week. In patients treated according to the protocol program using Viferon, the effectiveness of treatment is assessed according to the above principles. If in this category of patients during the control study 3 months after the start of therapy there is no positive effect, then Viferon can be replaced with Reaferon *, Roferon *.

The inductor of α-interferon meglumine acridone acetate (cycloferon *) is administered with chronic hepatitis at 6-10 mg / kg per day, 10 injections daily, then 3 times a week for 3 months as a complex therapy.

The antiviral drug tilorone (amixin) is prescribed to children over 7 years old in tablets of 0.125 orally after meals, the first 2 days daily, then 125 mg every other day - 20 tablets, then 125 mg once a week for 10-20 weeks. The course of treatment for HCA is 2-3 weeks, for CHB - 3-4 weeks.

In CHB against the background of viral replication, the antiviral chemotherapy drug lamivudine (zeffix, epivir *) in oral solution and tablets is recommended. Dosed at 3 mg / kg per day for children from 3 months of age, but not more than 100 mg orally 1 time per day for a course of 9-12 months. Tablets of 100 mg 1 time per day are prescribed to adolescents (16 years of age and older) by mouth, regardless of food intake.

In general, interferon therapy is effective in 40% of CHB patients and 35% of CHC patients, but in 10-30% of patients after the end of treatment, relapses of the disease are possible.

In severe chronic hepatitis C is prescribed glucocorticoids:prednisolone or methylprednisolone in tablets of 0.001; 0.0025 and 0.005 mg at 1-2 mg / kg per day in 2 divided doses without taking into account the daily rhythm. After achieving remission, the dose is reduced by 5-10 mg to a maintenance dose of 0.3-0.6 mg / kg per day: 10-15 mg / day of prednisolone or 8-12 mg / day of methylprednisolone.

Treatment effectiveness criteria:

. biochemical - the most informative is the determination of the level of ALT, and during treatment, the activity of ALT should be determined throughout the course and another 6 months after cancellation, and then every 3-6 months for 3 years;

Virological - determination of RNA, DNA of the virus using PCR;

Histological - the most informative for evaluating the effectiveness of treatment, but in practice they are not always realizable, especially in pediatrics.

Biochemical remissionat the end of treatment involves the normalization of enzyme levels immediately after the end of the course of therapy; complete remission- normalization of AST and ALT levels and the disappearance of RNA, DNA of the virus immediately after treatment; stable biochemical remission- maintenance of the normal value of transaminases after 6 months or more after stopping therapy; stable complete remission- maintenance of normal levels of AST and ALT and the absence of RNA, DNA of the virus 6 months after treatment.

If a stable complete remission is achieved, it is recommended to continue monitoring the patient for at least 2 years with a frequency of once every six months. In the remission phase (CVH integration phase), antiviral therapy is usually not carried out, treatment consists of the organization of the diet, regimen, the use of probiotics, enzymes, herbal remedies, laxatives according to indications to prevent gastrointestinal dysfunction and intestinal autointoxication.

Accompanying therapyis a symptomatic and pathogenetic treatment.

In order to stop cholestasis, ursodeoxycholic acid preparations (ursosan *, urdoksa *, ursofalk *) are used as monotherapy in the non-replicative phase of hepatitis, in the replicative phase - in combination with interferons up to 6-12 months at 10 mg / kg once a day before bedtime.

Hepatoprotectors with the ability to protect hepatocytes are prescribed in courses of up to 1.5-2 months. Repeated course - in 3-6 months according to indications.

Artichoke leaf extract (chophytol *) is a herbal remedy that has hepatoprotective and choleretic effects. Hofitol * is prescribed for children over 6 years old in 1-2 tablets or 1/4 tsp. solution for oral administration 3 times a day before meals, adolescents - 2-3 tablets or 0.5-1 tsp. solution 3 times a day, course - 10-20 days. Solution for intramuscular or intravenous slow administration - 100 mg (1 ampoule) for 8-15 days; average doses can be significantly increased, especially in inpatient treatment.

Hepatoprotector "Liv 52 *" is a complex of biologically active substances of plant origin; it is prescribed for children over 6 years of age 1-2 tablets 2-3 times a day, for adolescents 2-3 tablets 2-3 times a day.

Ademetionine (Heptral *) is a hepatoprotector that has choleretic and cholekinetic, as well as some antidepressant effect. Children are prescribed with caution orally, intramuscularly, intravenously. With intensive care in

the first 2-3 weeks of treatment - 400-800 mg / day intravenously slowly or intramuscularly; the powder is dissolved only in a special supplied solvent (L-lysine solution). For maintenance therapy - 800-1600 mg / day orally between meals, without chewing, preferably in the morning.

Prevention

The main preventive measures should be aimed at preventing infection with hepatitis viruses, therefore, early detection of patients with erased forms of the disease and their adequate treatment are required. Carriers of HBsAg require regular (at least once every 6 months) monitoring of biochemical and virological parameters in order to prevent the activation and replication of the virus.

Recombinant vaccines are used for vaccination against hepatitis B: "Biovac B *", "Engerix B *", "Euvax B *", "Shanvak-B *" and others. RD for newborns and children under 10 years of age - 10 mcg (0, 5 ml of suspension), for children over 10 years old - 20 μg (1 ml of suspension).

Newborns born to mothers - carriers of hepatitis B, along with the vaccine, are recommended to administer immunoglobulin against hepatitis B, while the drugs should be injected in different places. In accordance with the rules that exist in the Russian Federation, this category of children is vaccinated four times according to the scheme: 0 (on the birthday) -1- 2-12 months of age. Against hepatitis B, adolescents aged 11-13 years are necessarily vaccinated according to the same scheme.

Medical workers and people from risk groups for hepatitis B infection are widely vaccinated. Vaccination leads to a gradual decrease in the level of infection of the population of the Russian Federation with the hepatitis B virus.

A vaccine against hepatitis C has not yet been developed, and therefore the prevention of hepatitis C is based on the suppression of all possibilities of parenteral (including transfusion) infection.

Dispensary observation is described below.

Forecast

The likelihood of a complete recovery is negligible. With CHB, there is a long-term persistence of the pathogen virus, possibly a combination with an active pathological process. On average, after 30 years, 30% of patients with chronic active hepatitis B develop liver cirrhosis. Within 5 years, approximately every fourth patient with cirrhosis caused by hepatitis B develops liver function decompensation, another 5-10% of patients develop liver cancer (see Fig. 6-8). Without treatment, approximately 15% of patients with cirrhosis die within 5 years. In 1-1.5% of cases, cirrhosis is formed, and in the remaining 89%, long-term remission occurs with HBsAg carriage. With ΧΓD, the prognosis is unfavorable: in 20-25% of cases, the process flows into liver cirrhosis; release from the pathogen does not occur. CHC flows slowly, gently, without cessation of viremia for many years, with a periodic increase in the activity of transaminases and with a pronounced tendency to fibrosis. As the process progresses, liver cirrhosis and hepatocellular carcinoma develop.

AUTOIMMUNE HEPATITIS

ICD-10 code

K75.4. Autoimmune hepatitis.

AIH is a progressive hepatocellular inflammation of the liver of unknown etiology, characterized by the presence of periportal hepatitis, frequent association with other autoimmune diseases, increased concentration of immunoglobulins (hypergammaglobulinemia) and the presence of autoantibodies in the blood.

Like other autoimmune diseases, AIH is more common in females, with an overall incidence of about 15-20 cases per 100,000 population. In childhood, the proportion of AIH among chronic hepatitis ranges from 1.2 to 8.6%, observed at the age of 6-10 years. The ratio of girls to boys is 3-7: 1.

Etiology and pathogenesis

The pathogenetic mechanism of development of AIH is based on a congenital defect in membrane HLA receptors. Patients have a defect in the function of T-suppressors linked by the HLA haplotype, resulting in uncontrolled synthesis of IgG antibodies by B-lymphocytes that destroy the membranes of normal hepatocytes, and pathological immune reactions against their own hepatocytes develop. Often, not only the liver is involved in the process, but also large glands of external and internal secretion, including the pancreas, thyroid, and salivary glands. Genetic predisposition (immunoreactivity to autoantigens) is considered as the main factor in the pathogenesis of AIH, which, however, is not sufficient in itself. It is believed that triggering agents (triggers) are needed to implement the process, among which viruses (Epstein-Barr, measles, hepatitis A and C) and some drugs (for example, interferon preparations) and unfavorable environmental factors are considered.

Figure: 6-9.AIH pathogenesis

The pathogenesis of AIH is shown in Fig. 6-9. The effector mechanism of damage to hepatocytes is probably more related to the reaction of autoantibodies to hepato-specific antigens of hepatocytes than to direct T-cell cytotoxicity.

Classification

Currently, there are 3 types of AIH:

- type 1- the classic version, it accounts for 90% of all cases of the disease. Detect antibodies to anti-smooth muscle cells (Smooth Muscle Antibody- SMA) and nuclear antigens (liver-specific

squirrel - Antinuclear antibodies- ANA) in the title more than 1:80 in adolescents and more than 1:20 in children;

-type 2- makes up about 3-4% of all cases of AIH, most of the patients are children from 2 to 14 years old. Detect antibodies to liver and kidney microsomes (Liver Kidney Microsomes- LKM-1);

-type 3- characterized by the presence of antibodies to soluble hepatic antigen (Soluble Liver Antigen- SLA) and hepato-pancreatic antigen (LP).

Some features of AIG, taking into account the types, are presented in table. 6-8.

Table 6-8.Classification and features of AIH types

Clinical picture

The disease in 50-65% of cases is characterized by the sudden onset of symptoms similar to those in viral hepatitis. In some cases, it begins gradually and is manifested by increased fatigue, anorexia and jaundice. Other symptoms include fever, arthralgia, vitiligo (pigmentation abnormalities resulting in the disappearance of the melanin pigment in certain areas of the skin) and nosebleeds. The liver protrudes from under the edge of the costal arch by 3-5 cm and becomes denser, there is splenomegaly, the abdomen is enlarged (Fig. 6-10, a). As a rule, extrahepatic signs of chronic liver pathology are detected: spider veins, telangiectasias, palmar erythema. Some patients have a cushingoid appearance: acne, hirsutism and pink striae on the thighs and abdomen; 67% are diagnosed with other autoimmune diseases: Hashimoto's thyroiditis, rheumatoid arthritis, etc.

Diagnostics

Diagnosis is based on the detection of syndromes of cytolysis, cholestasis, hypergammaglobulinemia, an increase in IgG concentration, hypoproteinemia, a sharp increase in ESR, confirmed by the detection of autoantibodies against hepatocytes.

Characteristic hypersplenism syndrome,its signs:

Splenomegaly;

Pancytopenia (decrease in the number of all blood cells): anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia (with a sharp degree of severity, bleeding syndrome appears);

Compensatory bone marrow hyperplasia.

In diagnostics, instrumental research methods (scanning, liver biopsy, etc.) are of absolute importance.

Pathomorphology

Morphological changes in the liver with AIH are characteristic, but nonspecific. HCG, as a rule, turns into multilobular cirrhosis of the liver (Fig. 6-10, b); characterized by a high degree of activity: periportal

necrosis, port-portal or central-portal bridge necrosis, less often - portal or lobular hepatitis, mainly lymphocytic infiltration with a large number of plasma cells, the formation of rosettes (Fig. 6-10, c).

Figure: 6-10.AIH: a - a child with an outcome in liver cirrhosis; b - macropreparation: macronodular cirrhosis; c - micropreparation: histological picture (staining with hematoxylin-eosin; χ 400)

Differential diagnosis

Differential diagnosis is carried out with CHB, cholecystitis, Wilson-Konovalov disease, drug hepatitis, α-1-antitrypsin deficiency, etc.

A definite and probable AIH is distinguished. The first option is characterized by the presence of the above indicators, including an increase in autoantibody titers. In addition, there are no viral markers in the blood serum, damage to the bile ducts, copper deposition in the liver tissue, there are no indications for blood transfusion and the use of hepatotoxic drugs.

The probable variant of AIH is justified when the existing symptoms make it possible to think about AIH, but are not sufficient for making a diagnosis.

Treatment

The basis is immunosuppressive therapy. Prescribe prednisolone, azathioprine or their combinations, which make it possible to achieve clinical, biochemical and histological remission in 65% of patients within 3 years. Treatment is continued for at least 2 years until all criteria are in remission.

Prednisolone is prescribed at a dose of 2 mg / kg (maximum dose - 60 mg / day) with a gradual decrease by 5-10 mg every 2 weeks under weekly monitoring of biochemical parameters. In the absence of normalization of the level of transaminases, azithioprine is additionally prescribed at an initial dose of 0.5 mg / kg (the maximum dose is 2 mg / kg).

A year after the onset of remission, it is desirable to cancel immunosuppressive therapy, but only after a control puncture liver biopsy. Morphological examination should indicate the absence or minimal activity of inflammatory changes.

With the ineffectiveness of glucocorticoid therapy, cyclosporine (sandimmum neoral *) is used for oral administration from the first year of life, which is released in a solution of 100 mg in 50 ml in a vial, capsules of 10, 25, 50 and 100 mg,

the drug is prescribed at a dose of 2-6 mg / kg per day (no more than 15 mg / m 2 per week). Cyclophosphamide (cyclophosphamide *) is prescribed intravenously drip at a dose of 10-12 mg / kg once every 2 weeks, then in tablets of 0.05 g at 15 mg / kg once every 3-4 weeks, course dose - no more 200 mg / kg.

Primary resistance to treatment is observed in 5-14% of patients. They are primarily subject to consultation at liver transplant centers.

Prevention

Primary prevention has not been developed, secondary prevention consists in early diagnosis, dispensary observation of patients (described below) and long-term immunosuppressive therapy.

Forecast

The disease without treatment continuously progresses and does not have spontaneous remission - cirrhosis of the liver is formed. In type 1 AIH, glucocorticoids are more effective and the prognosis is relatively favorable: in many cases, it is possible to achieve long-term clinical remission. In type 2 AIH, the disease usually progresses rapidly to cirrhosis. Type 3 is not clinically well-defined and its course has not been studied.

With the ineffectiveness of immunosuppressive therapy, patients are shown liver transplantation, after which the 5-year survival rate is more than 90%.

Medicinal hepatitis

ICD-10 code

K71. Medicinal hepatitis.

Drug-related hepatitis is a toxic liver injury including idiosyncratic (unpredictable) and toxic (predictable) drug-induced liver disease associated with the intake of hepatotoxic drugs and toxic substances.

Etiology and pathogenesis

The liver plays an important role in the metabolism of xenobiotics (foreign substances). A group of enzymes located in the endoplasmic reticulum of the liver, known as cytochrome P450, is the most important family of metabolic enzymes in the liver. Cytochrome P450 assimilates about 90% of toxic and medicinal products.

Often, the liver becomes a target for their damaging effects. There are direct and indirect types of liver damage.

Direct type of liver damagedepends on the dose of the drug and is due to the effect of the drug itself on the cells of the liver and its organelles. To drugs with obligate dose-dependent hepatotoxic action include paracetamol and antimetabolites, leading to necrosis of hepatocytes. Direct liver damage can also be caused by tetracycline, mercaptopurine, azathioprine, androgens, estrogens, etc.

Indirect type of liver damagenot dependent on the dose of drugs, observed when taking nitrofurans, rifampicin, diazepam, meprobamate, etc. This type reflects the individual reaction of the child's body as a manifestation of hypersensitivity to drugs.

The liver is involved in the metabolism of various xenobiotics through biotransformation processes, which are divided into two phases.

. First phase- oxidative reactions involving cytochromes P450. During this phase, active metabolites can be formed, some of which have hepatotoxic properties.

. Second phase,during which the previously formed metabolites are conjugated with glutathione, sulfate or glucuronide, as a result of which non-toxic hydrophilic compounds are formed, which are excreted from the liver into the blood or bile.

Medicinal, or medication, hepatitis occupies a special place among the toxic liver damage. Their formation occurs more often as a result of the uncontrolled use of drugs (Fig. 6-11, a). Almost any drug can cause liver damage and the development of hepatitis of varying severity.

Toxins can be roughly divided into household and industrial toxins. Industrial poisons of organic nature (carbon tetrachloride, chlorinated naphthalene, trinitrotoluene, trichlorethylene, etc.), metals and metalloids (copper, beryllium, arsenic, phosphorus), insecticides (dichlorodiphenyltrichloroethane - DDT, carbofos, etc.) are isolated.

Figure: 6-11.Medicinal hepatitis: a - the formation of medicinal hepatitis with hepatocyte necrosis; b - histological picture of medicinal hepatitis after treatment of acute leukemia (staining with hematoxylin-eosin; χ 400)

Particularly severe forms of damage to hepatocytes develop when poisoning with substances such as paracetamol, pale toadstool poison, white phosphorus, carbon tetrachloride, all industrial poisons.

Clinical picture

Typical forms of liver damage with hepatotoxic effects of drugs are presented in table.

6-9.

Table 6-9.Most common hepatotoxic effects of drugs

Drug reactions can be transient, chronic hepatitis is rarely observed. Liver function tests may return to normal within a few weeks (up to 2 months) after drug withdrawal, but with cholestatic hepatitis, this period may increase to 6 months. Jaundice always indicates more severe liver damage, possibly the development of acute liver failure.

Diagnostics

The basis for the diagnosis of medicinal lesions of the liver is a carefully collected anamnesis of the drugs used, prescribed or used as self-medication. Usually, the time interval between taking the drug and the onset of the disease is from 4 days to 8 weeks.

A biopsy may be indicated if a previous liver pathology is suspected or if blood biochemical parameters (liver function tests) are not normalized after drug withdrawal.

Pathomorphology

Discomplexation of the hepatic tracts, severe protein (granular and balloon) degeneration of hepatocytes, polymorphism of hepatocyte nuclei, dystrophic and necrobiotic changes in the nuclei of hepatocytes are observed (Fig. 6-11, b).

Differential diagnosis

The possibility of toxic effects of drugs should be considered in the differential diagnosis of liver failure, jaundice. It is necessary to exclude other causes: viral hepatitis, diseases of the bile ducts, etc. In rare cases, it is necessary to carry out differential diagnostics with congenital metabolic diseases that can cause liver damage, type I glycogenosis (Gierke's disease),

Type III (measles disease), type IV (Andersen's disease), type VI (Hers disease). These diseases are due to the excessive accumulation of glycogen in the liver cells. Chronic liver lesions of drug origin should also be differentiated from lipidoses: Gaucher disease (based on the accumulation of nitrogen-containing cerebrosides in reticulohistiocytic cells) and Niemann-Pick disease (resulting from the accumulation of phospholipids in the cells of the reticuloendothelial system, mainly sphingomyelin). It is also necessary to exclude galactosemia and fructosemia.

Treatment

A prerequisite and main condition for treatment is a complete rejection of the use of a hepatotoxic drug.

A high-calorie (90-100 kcal / kg per day) diet rich in proteins (2 g / kg per day) and carbohydrates helps to restore the functional state of the liver. For therapeutic purposes, essential phospholipids are recommended, which have a membrane stabilizing and hepatoprotective effect, as well as inhibitors of lipid peroxidation processes. Thioctic acid is also prescribed

lot (lipoic acid *, lipamide *), which reduces the toxic effect of drugs due to its antioxidant effect; children over 12 years old - flavonoid silibinin (carsil *) 5 mg / kg in 3 divided doses (do not chew pills, take after meals with plenty of water).

Forecast

The prognosis depends on how quickly the drug that caused liver damage is canceled. Usually, clinical manifestations and changes in biochemical parameters are normalized within a few days, rarely weeks.

The prognosis is always serious when a picture of chronic liver damage with hepatocellular failure is formed.

Prevention of chronic hepatitis

Primary prevention has not been developed, while secondary prevention consists in early recognition and adequate treatment of children with acute viral hepatitis.

The widespread introduction of vaccination against hepatitis A and B will solve the problem of not only acute, but also chronic hepatitis.

CIRRHOSIS OF THE LIVER

ICD-10 codes

K71.7. Toxic liver damage with fibrosis and cirrhosis of the liver.

K74. Fibrosis and cirrhosis of the liver is cryptogenic. K74.3. Primary biliary cirrhosis. K74.4. Secondary cirrhosis of the liver. K74.5. Biliary cirrhosis, unspecified. K74.6. Other and unspecified cirrhosis of the liver. P78.3. Congenital cirrhosis.

Liver cirrhosis is a chronic progressive disease characterized by dystrophy and necrosis of the hepatic parenchyma, accompanied by its nodular regeneration, diffuse proliferation of connective tissue. It is a late stage of various diseases of the liver and other organs, in which the structure of the liver is disturbed, and the functions of the liver are not performed in full, as a result of which liver failure develops.

It is necessary to distinguish liver cirrhosis from its fibrosis. Fibrosis is a focal proliferation of connective tissue with various liver lesions: abscesses, infiltrates, granulomas, etc.

In economically developed countries, cirrhosis of the liver occurs in 1% of the population, is one of the 6 leading causes of death in patients aged 35 to 60 years. Every year in the world, 40 million people die from viral cirrhosis of the liver and hepatocellular carcinoma, which develops against the background of the carriage of the hepatitis B virus. It is more often observed in males, the ratio with the female sex is 3: 1.

Biliary atresia is one of the common causes of biliary cirrhosis in infants, with an incidence of 1 in 10,000-30,000 newborns.

Etiology and pathogenesis

Many diseases of the liver and other organs, long-term use of drugs (see Fig. 6-11, a, 6-12, a), etc. lead to cirrhosis of the liver. In addition, other diseases are important in the formation of cirrhosis:

Primary biliary cirrhosis;

Hereditary metabolic disorders (hemochromatosis, hepatolenticular degeneration, galactosemia, α-1-antitrypsin deficiency, etc.);

Violation of venous outflow from the liver (Budd-Chiari syndrome, veno-occlusive disease, severe right ventricular heart failure), etc.

Atresia of the biliary tractrefer to developmental anomalies, which in most cases is associated with intrauterine hepatitis, often caused by one of the reoviruses. In some children, the occurrence of this malformation is due to unfavorable factors that acted at 4-8 weeks of intrauterine life. Usually, these children have malformations of other organs (more often the kidneys, heart, spine). Some children have an association with trisomies on the 13th and 18th pairs of chromosomes. Atresia is characterized by complete closure of the intra-, extrahepatic bile ducts in various forms. More often (in 70-80% of cases), the intrahepatic form of atresia occurs.

One of the main signs and complications of liver cirrhosis is portal hypertension syndrome,which occurs due to an increase in pressure in the portal vein (a vein that brings blood from the abdominal organs to the liver) more than 5 mm Hg. As a result of increased pressure in the portal vein, blood cannot flow from the abdominal organs and blood stagnation occurs in these organs (Fig. 6-12, b).

The approximate cellular composition of the liver: 70-80% - hepatocytes, 15% - endothelial cells, 20-30% - Kupffer cells (macrophages), 5-8% - Ito cells (Fig. 6-13, a). Ito cells(synonyms: stellate cells of the liver, fat-storing cells, lipocytes) located in the perisinusoidal space of Disse play a key role in the pathogenesis of liver cirrhosis. Being the main cells of the connective tissue in the liver, they form the extracellular matrix, normally accumulating lipids. When the liver is damaged, Ito cells begin to produce type I collagen and cytokines, acquiring fibroblast-like properties (Fig. 6-13, b). This process takes place with the participation of hepatocytes and Kupffer cells.

Figure: 6-12.Liver cirrhosis: a - etiological factors; b - the portal system of the liver and the mechanism of the formation of portal hypertension

The pathogenesis of liver cirrhosis is shown in Fig. 6-13, b, but in approximately 10-35% of patients, the etiology and pathogenesis of liver cirrhosis remain unknown.

1 Figure: 6-13.a - part of the hepatic lobule and its cellular composition; b - pathogenesis of liver cirrhosis

Changes in the liver with cirrhosis are usually diffuse, only with biliary cirrhosis they can be focal. The death of hepatocytes, associated with inflammation and fibrosis, leads to a disruption of the normal liver architectonics: loss of the normal hepatic vasculature with the development of portocaval shunts and the formation of regeneration nodes of preserved hepatocytes (Fig. 6-14, a), and not normal hepatic lobules detected in autopsy material or in vivo using MRI (Fig. 6-14, b).

Figure: 6-14.Changes in the liver in cirrhosis: a - a macro-preparation of micronodular cirrhosis of the liver; b - MRI of the liver: the arrow indicates the regeneration node

Classification

Allocate extrahepatic biliary atresia (without or in combination with gallbladder atresia), intrahepatic bile duct atresia (without or in combination with extrahepatic biliary atresia), total atresia. The classification of liver cirrhosis is presented in table. 6-10.

Table 6-10.Classification of liver cirrhosis

Clinical picture

With primary biliary cirrhosis of the liver, which is manifested by inflammation of the bile ducts of the liver with impaired outflow of bile, jaundice, itching, fever and other symptoms are observed. Biliary cirrhosis, associated with congenital atresia of the biliary tract, forms quickly, leading to death in the absence of surgery for health reasons.

Alcoholic cirrhosis of the liver develops in people who consume alcoholic beverages in excessively large doses for a long time; it is not considered in childhood hepatology.

Cirrhosis of the liver in older children develops slowly and may initially be asymptomatic. The signs indicated in table. 6-11, as a rule, develop gradually and are invisible for a child who has a chronic disease of the liver or other organs for a long time, and for his parents.

Hepatomegaly is observed at the onset of the disease. Gradual destruction of hepatocytes, fibrosis as the underlying disease progresses lead to a decrease in the size of the liver.A decrease in liver size is especially characteristic in cirrhosis caused by viral and autoimmune hepatitis.

Table 6-11.Signs of liver cirrhosis

Complications of liver cirrhosisare portal hypertension syndrome (Table 6-12), varicose veins of the lower extremities, bleeding from the dilated veins of the esophagus, hepatic coma.

Table 6-12.Diagnosis of portal hypertension syndrome

Varicose veins- complication of liver cirrhosis, manifested by pain in the extremities, visible and significant increase in veins. Bleeding from dilated esophageal veinsmanifested by the discharge of blood from the mouth and / or blackening of the stool. Hepatic coma- brain damage that develops as a result of the accumulation of a large amount of toxic substances in the blood, as a rule, develops with decompensated cirrhosis; the main signs of the syndrome of hepatic cell failure are presented in table. 6-13.

Table 6-13.Signs of hepatocellular failure syndrome

Diagnostics

In the biochemical analysis, initially the syndromes of cytolysis, cholestasis, inflammation are detected, and later - hepatodepressive syndrome (see Table 1-8).

When ultrasound describes micronodular (Fig. 6-15, a) or macronodular (Fig. 6-15, b) types of liver cirrhosis. Histological synonyms for these names:

Small-nodular cirrhosis is characterized by the formation of small nodules (about 1 mm in diameter);

Large-nodular cirrhosis - large fibrous scars are revealed in areas of previous destruction of the hepatic architectonics.

Pathomorphology

A classical macropreparation of the liver, clearly representing biliary cirrhosis of the liver, is shown in Fig. 6-15, c.

During the life of a child, only a biopsy can accurately indicate liver cirrhosis, in which severe dystrophic changes in hepatocytes, cholestasis, foci of proliferation of connective tissue (fibrous nodes), between which arelets are located normal liver cells, are revealed (Fig. 6-15, d).

Differential diagnosis

Treatment

The main principles for the treatment of liver cirrhosis are as follows.

Elimination of the causes leading to cirrhosis (etiotropic treatment): antiviral therapy (viral hepatitis), withdrawal symptoms (alcoholic cirrhosis), drug withdrawal (drug hepatitis).

Figure: 6-15.Liver cirrhosis according to ultrasound data: a - micronodular; b - macronodular: congenital atresia of the bile ducts with the formation of cirrhosis: c - macropreparation; d - micropreparation (staining with hematoxylin-eosin; χ 400)

Diet therapy.

Therapy of the developed complications of liver cirrhosis: symptomatic treatment of hepatic encephalopathy, portal hypertension syndrome, etc.

Pathogenetic: removal of excess iron and copper (hemochromatosis, Wilson-Konovalov disease), immunosuppressive therapy (AIH), treatment of cholestasis (primary biliary cirrhosis).

With an established diagnosis biliary atresiasurgical treatment: choledochojejunostomy or protoenterostomy (Kasai's operation - creating a direct anastomosis between the decapsulated open surface of the liver in

area of \u200b\u200bthe gate and intestines), transplantation of a part of the liver. Treatment is supportive before surgery. Glucocorticoids are ineffective, as are other drugs. At the same time, vitamin K should be administered parenterally once a week, and courses of hepatoprotectors, vitamins E, D should be carried out periodically.

Treatment of complications of liver cirrhosis

Strict bed rest;

Hyponosodium diet: with minimal and moderate ascites - limiting the intake of table salt to 1.0-1.5 g / day; with tense ascites - up to 0.5-1.0 g / day;

Limiting fluid intake to 0.8-1.0 liters per day;

Diuretic therapy: aldosterone antagonists and natriuretics;

Therapeutic paracentesis (3-6 liters) with intravenous administration of albumin solution (at the rate of 6-8 g per 1 liter of ascitic fluid removed);

Ultrafiltration using a peritoneal-venous shunt, transjugular intrahepatic portosystemic shunt;

Liver transplant.

DiureticsHydrochlorothiazide (hypothiazide *) in tablets and capsules is administered orally to children from 3 to 12 years old at 1-2 mg / kg per day in 1 dose. Hypokalemia can be avoided by taking medications containing potassium or eating foods rich in potassium (fruits, vegetables).

Spironolactone (veroshpiron *, aldactone *, veropilactone *) in tablets, capsules, initial daily dose - 1.33 mg / kg, maximum - 3 mg / kg in 2 divided doses, or 30-90 mg / m2, course - 2 weeks ... Contraindicated in infancy.

Furosemide (lasix *) in tablets of 40 mg and granules for suspension preparation, ampoules of 1% - 2 ml. Newborns are prescribed 1-4 mg / kg per day 1-2 times, 1-2 mg / kg intravenously or intramuscularly 1-2 times a day, children - 1-3 mg / kg per day, adolescents - 20 -40 mg / day

Diuretics are prescribed in the morning. It is necessary to control the level of potassium in the blood serum, ECG.

The criterion for the effectiveness of the therapy is a positive water balance, amounting to 200-400 ml / day with a small volume of ascites and 500-800 ml / day - with edematous ascitic syndrome in older children. Paracentesisperform according to strict indications (with a large amount of liquid) with the simultaneous administration of albumin in an amount of 4-5 g IV. If drug therapy is ineffective, surgical treatment (shunting) is possible.

Hemostatic therapy (ε-aminocaproic acid, vicasol *, calcium gluconate, dicinone *, erythrocyte mass).

Restoration of the volume of circulating blood (albumin solution, plasma).

Pharmacological reduction of portal pressure (vasopressin, somatostatin, octreotide).

Mechanical tamponade of the esophagus (Sengstaken-Blackmore probe).

Endoscopic methods for stopping bleeding (sclerotherapy with ethanolamine, polidocanol, ligation of vein trunks).

Transjugular intrahepatic portosystemic shunt.

Prevention of stress gastrointestinal ulcers (blockers of H2-histamine receptors, PPI).

Prevention of hepatic encephalopathy (lactulose, siphon enemas).

Prevention of spontaneous bacterial peritonitis (antibiotics).

The main pharmacological agents for hemorrhagic syndrome

ε-Aminocaproic acid for intravenous administration and in granules for the preparation of a suspension for oral administration, the daily dose for children under 1 year old is 3 g; 2-6 years old - 3-6 g, 7-10 years old - 6-9 g.

Menadione sodium bisulfate (vicasol *) 1% solution is prescribed for children under 1 year old - 2-5 mg / day, 1-2 years - 6 mg / day, 3-4 years - 8 mg / day, 5-9 years - 10 mg / day, 10-14 years old - 15 mg / day. The duration of treatment is 3-4 days, after a 4-day break, the course is repeated.

Etamsylate (dicinone *) is produced in tablets of 250 mg and in the form of a 12.5% \u200b\u200bsolution in ampoules of 2 mg (250 mg in an ampoule) for intramuscular and intravenous administration. For bleeding, children under 3 years old are injected with 0.5 ml, 4-7 years old - 0.75 ml, 8-12 years old - 1-1.5 ml and 13-15 years old - 2 ml. This dose is repeated every 4-6 hours for 3-5 days. In the future, treatment with dicinone * can be continued in tablets (daily dose - 10-15 mg / kg): children under 3 years old - 1/4 tablet each, 4-7 years old - 1/2 tablet, 8-12 years old - 1 tablet each and 13-15 years old - 1.5-2 tablets 3-4 times a day.

A remedy for strengthening the vascular wall - flavonoid troxerutin, ascorbic acid + rutoside (ascorutin *).

To reduce portal pressure, desmopressin (minirin *), an analogue of the natural hormone arginine-vasopressin, is used at 100-200 mg at night.

Treatment malignant neoplasm of the livercarried out by specialists of the oncological center. Indications for splenectomy

Segmental extrahepatic portal hypertension.

Severe hypersplenism with hemorrhagic syndrome.

Lagging in the physical and sexual development of children with liver cirrhosis.

Giant splenomegaly with severe pain syndrome (heart attacks, perisplenitis).

Treatment spontaneous bacterial peritonitiscarried out with cephalosporins of the III-IV generation.

A radical treatment for liver cirrhosis is liver transplantation.

Prevention

The basis secondary preventionis the timely etiotropic and pathogenetic treatment of acute and chronic hepatitis.

Prevention of cirrhosis per se tertiaryand quaternary,since they carry out treatment aimed at stabilizing the pathological process in the liver, preventing exacerbations, reducing the risk of developing and progression of complications. Children should be under dynamic supervision in specialized clinics and centers, and on an outpatient basis - under the supervision of a pediatrician and gastroenterologist. Immunoprophylaxis is carried out strictly individually.

Prevention of complications, for example, the first bleeding from varicose veins of the esophagus, is possible thanks to endoscopic examination at least once every 2-3 years in order to dynamically observe their probable development. The condition of patients with the initial stage of esophageal varicose veins is monitored endoscopically 1 time in 1-2 years. Prophylactic treatment is carried out with moderate and severe degrees.

Forecast

The prognosis of liver cirrhosis is unfavorable and, as a rule, uncertain and unpredictable, since it depends on the cause of cirrhosis, the patient's age, the stage of the disease, and the possibility of unforeseen fatal complications. By itself, cirrhosis of the liver is incurable (except for those cases when a liver transplant was performed), however, correct treatment of cirrhosis allows for a long time (20 years or more) to compensate for the disease. Compliance with diet, traditional and alternative methods of treatment (Fig. 6-16), giving up bad habits significantly increase the patient's chances of compensating for the disease.

Figure: 6-16.Treatment options for patients with cirrhosis

Without surgical treatment, children with biliary atresia die at the age of 2-3. The earlier the operation is performed, the better the prognosis. About 25-50% of early-operated children survive 5 years or more when they receive a liver transplant. The outcome depends on the presence or absence of an inflammatory and sclerotic process in the liver.

LIVER FAILURE

ICD-10 codes

K72. Liver failure. K72.0. Acute and subacute hepatic failure. K72.1. Chronic liver failure. K72.9. Hepatic impairment, unspecified.

Liver failure is a complex of symptoms characterized by a violation of one or more functions of the liver, resulting from damage to its parenchyma (hepatocellular or hepatocellular failure syndrome). Portosystemic or hepatic encephalopathy is a symptom complex of central nervous system disorders that occurs in hepatic failure with profound impairment of numerous vital functions of the liver.

Mortality from liver failure is 50-80%. In acute liver failure, the development of hepatic encephalopathy is possible, which is rare in acute liver diseases, but the mortality rate can reach 80-90%.

Etiology and pathogenesis

Acute liver failureoccurs in severe forms of viral hepatitis A, B, C, D, E, G, poisoning with hepatotropic poisons (alcohol, some drugs, industrial toxins, mycotoxins and aflatoxins, carbon dioxide, etc.). Its causes may be herpes viruses, cytomegalovirus, infectious mononucleosis virus, simple and shingles, Coxsackie virus, measles causative agent; septicemia with liver abscesses. Acute liver failure is described in toxic hepatosis (Reye's syndrome, condition after the small intestine is disconnected), Wilson-Konovalov's disease, Budd-Chiari syndrome.

Budd-Chiari Syndrome(ICD-10 code - I82.0) develops due to progressive narrowing or closure of the hepatic veins. Due to thrombophlebitis of the umbilical vein and the Arancian duct, which flows into the mouth of the left hepatic vein, Budd-Chiari syndrome can begin in early childhood. As a result, stagnation develops in the liver with compression of the liver cells.

Reye's syndrome(ICD-10 code - G93.7) - acute encephalopathy with cerebral edema and fatty liver infiltration that occurs in previously healthy newborns, children and adolescents (more often at the age of 4-12 years), associated with a previous viral infection (for example, varicella smallpox or influenza type A) and taking medications containing acetylsalicylic acid.

Chronic liver failureis a consequence of the progression of chronic liver diseases (hepatitis, liver cirrhosis, malignant liver tumors, etc.). The main etiological factors are indicated in Fig. 6-17, a.

At the heart of pathogenesis liver failurethere are two processes. First, severe dystrophy and widespread necrobiosis of hepatocytes lead to a significant decrease in liver function. Secondly, due to the numerous collaterals between the portal and vena cava, a significant part of the absorbed toxic products enters the systemic circulation bypassing the liver. Poisoning is caused by non-neutralized protein breakdown products, metabolic end products (ammonia, phenols).

Emergence hepatic encephalopathyin liver failure it is associated with disorders of homeostasis, acid-base state and electrolyte composition of the blood (respiratory and metabolic alkalosis, hypokalemia, metabolic acidosis, hyponatremia, hypochloremia, azotemia). Cerebrotoxic substances enter the systemic circulation from the gastrointestinal tract and liver: amino acids and their decay products (ammonia, phenols, mercaptans); products of hydrolysis and oxidation of carbohydrates (lactic acid, pyruvic acid, acetone); products of impaired fat metabolism; false neurotransmitters (asparagine, glutamine), which have toxic effects on the central nervous system. The mechanism of damage to brain tissue is associated with dysfunction of astrocytes, which make up approximately 30% of brain cells. Astrocytes play a key role in regulating the permeability of the blood-brain barrier, in ensuring the transport of neurotransmitters to the neurons of the brain, as well as in the destruction of toxic substances (in particular, ammonia) (Fig. 6-17, b).

Figure: 6-17.Chronic hepatic failure and hepatic encephalopathy: a - etiology of hepatic failure; b - the mechanism of formation of hepatic encephalopathy

Ammonia exchange.In healthy people, ammonia is converted to uric acid in the liver in the Krebs cycle. It is required in the reaction of the conversion of glutamate to glutamine, which is mediated by the enzyme glutamate synthetase. With chronic liver damage, the number of functioning hepatocytes decreases, creating the prerequisites for hyperammonemia. When portosystemic shunting occurs, ammonia, bypassing the liver, enters the systemic circulation - hyperammonemia occurs. Ammonia entering

into the brain, leads to disruption of the functioning of astrocytes, causing morphological changes in them. As a result, with liver failure, cerebral edema occurs, and intracranial pressure rises.

Under conditions of liver cirrhosis and portosystemic shunting, the activity of glutamatesynthetase of skeletal muscles increases, where the process of ammonia destruction begins. This explains the decrease in muscle mass in patients with liver cirrhosis, which, in turn, also contributes to hyperammonemia. The processes of metabolism and excretion of ammonia also occur in the kidneys.

Clinical picture

The clinical picture is manifested by disorders of consciousness and cognitive functions, drowsiness, monotonous speech, tremors, and discoordination of movements. Particularly important signs are a rapid decrease in the size of the liver, its softening and tenderness to palpation. Table 6-14 briefly summarize the clinical manifestations of the stages of liver failure and encephalopathy, the differences between acute and chronic liver failure - in table. 6-15.

Table 6-14.Classification of stages of liver failure and encephalopathy

Table 6-15.Differential diagnosis of acute and chronic liver failure

Hepatic coma is preceded by general excitement, which turns into depression of consciousness: stupor and stupor, then its complete loss occurs. Meningeal phenomena, pathological reflexes (grasping, sucking), motor restlessness, convulsions appear. Breathing becomes irregular, like Kussmaul or Cheyne-Stokes. The pulse is small, irregular. From the mouth and from

hepatic odor emanates from the skin (fetor hepatica),due to the release of methyl mercaptan; jaundice and hemorrhagic syndrome increase, ascites, hypoproteinemic edema increase (Fig. 6-18, a). Clinical manifestations of decompensated and terminal stages are clearly shown in Fig. 6-18, b-d. The term "malignant form" (the most severe form) denotes a qualitatively new clinical condition that occurs in patients with viral hepatitis B if they develop massive or submassive liver necrosis.

Figure: 6-18.Hepatic failure: a - clinical manifestations; a and b - decompensated stage; c - terminal stage ("floating eyeball"); d - hepatic coma

Over the next 2-3 days, a deep hepatic coma develops. Sometimes a coma occurs, bypassing the stage of excitement.

Diagnostics

Laboratory and instrumental studies are carried out.

A general blood test reveals anemia, leukocytosis, thrombocytopenia, and increased ESR.

In a biochemical study, bilirubinemia, azotemia, hypoalbuminemia, hypocholesterolemia are diagnosed, the levels of ALT, AST, ALP increase, the levels of fibrinogen, potassium, sodium, prothrombin index decrease, and metabolic acidosis is noted.

Ultrasound, CT scan of the liver reveals a change in the size and structure of the liver parenchyma.

Pathomorphology

Morphological changes in the liver concern all its tissue components: parenchyma, reticuloendothelium, connective tissue stroma, and to a lesser extent - biliary tract.

Distinguish three variants of the acute form of the disease:

Acute cyclic form;

Cholestatic (pericholangiolytic) hepatitis;

Massive liver necrosis.

The severity of morphological changes depends on the severity and etiology of the disease (Fig. 6-19, a, b). At the height of the disease, alternative, exudative processes prevail, during the period of recovery - the processes of proliferation and regeneration.

Figure: 6-19.Liver necrosis, macro- and micropreparations: a - the etiology is unknown; b - adenoviral etiology; c - χ 250; d - χ 400 (staining with hematoxylin-eosin)

In cholestatic (pericholangiolytic) hepatitis, morphological changes concern mainly intrahepatic bile ducts (cholangiolitis and pericholangiolitis).

Liver necrosis is an extreme degree of changes in the liver, which can be massive, when almost the entire hepatic epithelium dies or a slight border of cells is preserved along the periphery of the lobules, or submassive, in which most hepatocytes undergo necrobiosis, mainly in the center of the lobules (Fig. 6-19 , c, d).

Differential diagnosis

For the purpose of differential diagnosis, it is necessary to exclude extrahepatic causes of symptoms from the central nervous system. Determine the level of ammonia in the blood upon admission to the hospital of a patient with liver cirrhosis and signs of CNS damage. It is necessary to establish the presence in the patient's history of such pathological conditions as metabolic disorders, gastrointestinal bleeding, infections, constipation.

When symptoms of hepatic encephalopathy occur, differential diagnosis is carried out with diseases, which include the following.

Intracranial pathological conditions: subdural hematoma, intracranial bleeding,

stroke, brain tumor, brain abscess.

Infections: meningitis, encephalitis.

Metabolic encephalopathy, developed against the background of hypoglycemia, electrolyte disturbances, uremia.

Hyperammonemia caused by congenital anomalies of the urinary tract.

Toxic encephalopathy caused by alcohol intake, acute intoxication, Wernicke's encephalopathy.

Toxic encephalopathy, which has arisen on the background of taking medications: sedatives and antipsychotics, antidepressants, salicylates.

Postconvulsive encephalopathy.

Treatment

Treatment consists in limiting the amount of protein in the diet, prescribing lactulose. Patients with hepatic encephalopathy are candidates for liver transplantation.

In the complex of therapeutic measures for liver failure, there are stages (Fig. 6-20), and also distinguish basic (standard) therapy and a number of more radical means aimed at cleansing the body of toxic metabolic products, as well as replacing (temporary or permanent) functions the affected liver.

Basic therapyacute liver failure is aimed at correcting the electrolyte, energy balance, acid-base state, vitamins and cofactors, disorders of the blood coagulation system, hemocirculation, eliminating hypoxia, preventing complications, preventing the absorption of putrefactive decay products from the intestine. The basic therapy includes the use of glucocorticoids.

General principles of management of a patient with acute liver failure

Individual post of a nurse.

Monitor urine output, blood glucose and vital signs every hour.

Figure: 6-20.Stages of hepatic encephalopathy treatment

Serum potassium control 2 times a day.

Blood test, determination of the content of creatinine, albumin, assessment of the coagulogram daily.

Prevention of bedsores.

General principles of management of a patient with chronic liver failure

Active monitoring of the patient's condition, taking into account the severity of symptoms of encephalopathy.

Weighing the patient daily.

Daily assessment of the balance of fluids drunk and excreted per day.

Daily determination of blood tests, electrolytes, creatinine.

Determination of the content of bilirubin, albumin, activity of AST, ALT, ALP 2 times a week.

Coagulogram, prothrombin content.

Assessment of the necessity and possibility of liver transplantation in the final stage of liver cirrhosis.

Hepatic encephalopathy treatment

Elimination of provoking factors.

Stopping gastrointestinal bleeding.

Suppression of the growth of proteolytic microflora in the colon and treatment of infectious diseases.

Normalization of electrolyte disorders.

Reducing the degree of hyperammonemia:

a) reduction of ammoniacal substrate:

Cleansing the gastrointestinal tract (siphon enemas, laxatives);

Decreased protein intake;

b) binding of ammonia in the blood:

Ornithine (hepa-merz *);

c) suppression of the formation of ammonia:

Broad-spectrum antibiotics;

Acidification of intestinal contents with lactulose. To reduce ammonia, enemas are recommended.

or using laxatives to empty your bowels at least 2 times a day. For this purpose, lactulose (normase *, duphalac *) is prescribed in syrup, 20-50 ml orally every hour until diarrhea appears, then 15-30 ml 3-4 times a day. For use in an enema, the preparation is diluted up to 300 ml in 500-700 ml of water.

Before the patient is discharged from the hospital, the dose of lactulose should be reduced to 20-30 ml at night, with possible subsequent cancellation at the outpatient stage.

TO radical treatment methodsinclude the following measures for the massive removal of toxic products from the patient's blood.

Guided hemodilution.

Plasmapheresis.

Replacement blood transfusion.

Temporary (or permanent) replacement of the patient's liver by extracorporeal connection of xeno liver (porcine), cross circulation.

Hetero- and orthotopic liver transplantation.

Prevention

The best way to prevent liver failure is to prevent the risk of developing cirrhosis or hepatitis. This requires specific immunization, it is important to observe a healthy lifestyle, personal hygiene rules, and diet therapy.

The introduction of a specific immunoglobulin in case of accidental transfusion of infected blood and at the birth of a child to a mother who is a carrier of HBsAg or a patient with hepatitis B will allow passive immunization. Active immunization - vaccination of a child in the first day after birth, unvaccinated children of any age, as well as persons from risk groups: professional (doctors, emergency workers, military, etc.), persons on programmed hemodialysis, etc. (revaccination every 7 years). Vaccination against viral hepatitis B protects against hepatitis D.

Forecast

By eliminating the cause of the liver failure, the manifestations of hepatic encephalopathy can be reduced. Chronic hepatic coma is fatal, but with acute hepatocellular failure, recovery is sometimes possible. With the development of hepatic encephalopathy, mortality can reach 80-90%.

The liver is the main (although not the only) organ in which drugs and other xenobiotics are metabolized (you can read about drugs affecting the liver here).
There are 3 main types of interactions and interactions between drugs and the liver:
1) metabolic transformations (biotransformation) of drugs in the liver;
2) the effect of liver disease on drug metabolism;
3) the damaging effect of drugs on the liver.
This must be taken into account in clinical psychiatry and narcology due to the widespread use, often in medium and high doses, of psychotropic and other drugs that have hepatotoxic properties or (more often) create a high metabolic load on hepatocytes.
Often, it is not the drug that has hepatotoxic properties, but its metabolite, which is formed during the biotransformation of the drug in the liver. A typical example of this is paracetamol (acetaminophen). The formation of toxic derivatives is characteristic of drugs metabolized with the participation of the cytochrome P450 family. It is characteristic that the toxic effects of drug metabolites may accompany their pharmacological activity.
Drug metabolism usually consists of two stages: non-synthetic (1) and synthetic (2) reactions.
At the first (initial) stage, non-synthetic reactions occur, including oxidation, reduction, hydrolysis, or a combination of these processes. The resulting drug metabolites can have pharmacological activity, sometimes higher than the parent substance.
At the second (final) stage of metabolism, synthetic reactions take place, during which an intermediate metabolite combines with an endogenous substrate and forms a highly polar product excreted in urine or bile (polarity is a property that determines the ability of a substance to excrete). The main synthetic reactions are conjugation with glucuronic acid, conjugation with amino acids (glutamine and glycine), acetylation, sulfation, and methylation. The products of synthetic reactions usually (but not always) show no pharmacological activity.
Oxidation reactions take place with the participation of a complex complex of microsomal enzymes, the basis of which is hemoprotein cytochrome P450.
There is a limiting metabolic rate for drugs and psychoactive substances. The kinetic properties of enzymes involved in the metabolism of xenobiotics are such that the rate of reactions catalyzed by them cannot exceed a certain value. At therapeutic doses of drugs (or low doses of surfactants), only a small part of the active sites of the enzyme is involved in the reaction. With an increase in the plasma concentration of the substance being metabolized, the active centers of the enzyme are almost completely occupied in the reaction. The intensity of biotransformation ceases to increase in proportion to the concentration of the substance and reaches the saturation threshold. Similar patterns are observed in the metabolism of some anticonvulsants and ethanol.

Reactive hepatitis according to ICD 10 is a chronic disease. It develops as a side reaction to another chronic disease. As a rule, the reason lies in infections and pathologies of the gastrointestinal tract. As a result, against the background of the main ailment, the liver becomes inflamed, and organ dystrophy develops. Disease code according to ICD K75.2.

To begin with, you need to deal with these numbers and an incomprehensible medical abbreviation. ICD is the international medical classification of diseases, and 10 stands for the number of revisions. The fact is that the final version of the handbook was adopted a whole century ago, and before that it was revised 9 times and on the tenth it was finally installed.

Modern doctors and scientists use a teaching aid compiled in the last century to facilitate the maintenance of medical records, card indexes and registration of sick leaves. The International Code List makes it easy to enter statistics both manually and into computers. Technology, thus, is capable of processing huge amounts of information, and in general, and on a specific medical institution, and on the diseases themselves with their varieties.

Take, for example, reactive hepatitis according to ICD-10 code K75.2. Encrypted combinations of characters have their meaning, meaningful and orderly. The first is a specific letter. It means that the disease belongs to any system of the body. In this case, K, here we are talking about the digestive organs. The next couple of numbers tell us about the organ itself or a group of organs. Liver diseases have a range of K70 – K77. After the dot comes a type of disease, in this case, reactive hepatitis.

Such statistical records without unnecessary amounts of information and other clarifications will indicate the patient's illness. The attending physician puts a special mark in his sick-list, according to which, after consulting the reference book, you can voice a detailed diagnosis.

The advantages of such an international disease coding system:

• simplicity in medical records of diseases;
• reducing the time to search for a disease by reference;
• optimization of the process of machine registration of patients;
• complete computerization of statistical data by regions, cities, countries.

Such a system allows, without unnecessary problems, in a more simplified way to analyze the incidence rate both on a national scale and on a regional scale. It also helps in the process of developing new medicines, determining the demand for vaccines, and, accordingly, the volume of their production, etc.

Speaking about the disease itself, it is necessary to understand directly the diagnosis of hepatitis. The ending "-it" speaks of the inflammatory process in the organ, and the root of the word - that this organ is the liver.

So, hepatitis is an inflammation of the liver. It comes in two varieties - viral and non-viral - depending on the nature of the occurrence.

Specifically, reactive hepatitis KSD considers as a chronic form of the disease, developed under the influence of another serious illness. It is not a question of a viral pathogen, but of liver damage due to problems in other organs of the digestive system.

The most common causes of reactive hepatitis are:

• stomach ulcer;
• stomach cancer;
• duodenal ulcer;
• pancreatitis;
• chronic enterocolitis;
• dumping syndrome;
• gallbladder disease;
• rheumatism;
• scleroderma;
• lupus erythematosus;
• rheumatoid arthritis;
• diabetes;
• hemolytic anemia;
• polyarthritis nodosa;
• thyrotoxicosis;
• burns;
• intoxication.

As for the pathogenesis, the liver begins to change due to impaired detoxification function. Toxins and antigens now freely enter the hepatic artery and portal vein. Liver cells do not receive their norm of nutrients, thus, fatty and protein degeneration of the organ is observed. The liver is affected locally, the foci are surrounded by lymphocytes, macrophages, neutrophils.

According to the location of inflammation on the liver, several types of reactive hepatitis are distinguished: lobular and portal. In the first case, the parenchyma is affected, and there are several foci of this lesion. There is edema with a low degree of infiltration. After a while, fibrosis joins.

What is remarkable about hepatitis, of any type, is a latent development. A person can be sick with hepatitis for a long time and not know it. In most cases, the manifestations can be ignored until the moment when the diagnosis is found during some third-party examination.

This "accidental surprise" is not uncommon. By its inconspicuousness, inflammation of the liver differs from inflammatory processes that affect other organs. Meningitis and rhinitis can be recognized immediately by the mucus from the nasal passages. Gastritis affects the stomach, causing pain in the upper abdomen; arthritis makes you know the pain in the joints, pyelonephritis immediately hits the kidneys, the lower back and the urinary canal hurt. The same with otitis media (ear inflammation), conjunctivitis (eye inflammation), sinusitis, colitis and other similar diseases.

Even when the disease is detected, it is mostly asymptomatic. If signs appear, then the stage of development of the process has already gone far.

The manifestations are weak, unexpressed:

1. Pain in the right hypochondrium, not too sharp, accompanied by heaviness.
2. General weakness of the body.
3. The liver is enlarged, but not much.
4. Sometimes painful sensations are possible on palpation.
5. In some cases, pulling pains in muscles and joints are possible.
6. Dyspepsia - nausea, vomiting, weight loss due to lack of appetite.
7. Headache, fatigue.
8. It is difficult to fall asleep at night, and in the daytime it constantly tends to sleep.
9. Apathy, irritability, depression.
10. Itching is possible.
11. The skin and mucous membranes are painted in a yellowish tint.

Prolonged reactive hepatitis will only worsen symptoms. But in general, the prognosis is more favorable, the changes affecting the liver are reversible. Recovery, although long, is possible.

To begin with, a specialist hepatologist conducts diagnostic measures:

1. Interview and examination - identification of dominant complaints and clinical signs.
2. Laboratory tests - general, biochemical, enzyme immunoassay.
3. Instrumental diagnostics - ultrasound (ultrasound), biopsy followed by the study of a fragment, scintigraphy (a radioisotope technique, the mechanism of which consists in introducing a special drug into the body, which is monitored by hardware during its removal).

After detecting changes in the liver (it does not matter if the patient is an adult or a child), treatment should be started.

Therapy takes place according to three compulsory principles:

1. Elimination is the isolation of the body from the provoking factor. In the case of reactive hepatitis, it is logical to first cure the underlying disease, and then make sure that repeated contact with pathogens does not occur.
2. Diet adjustment is a mandatory exclusion of alcohol, fatty foods and fried foods. It is necessary to remove spices and seasonings from the diet, all kinds of synthetic food additives, flavor enhancers. A complete diet should be balanced in calories and benefits. It is preferable to give the predominant role to vegetables and fruits, combining them with dietary meat and fish.
3. Drug therapy - here a variation of the liver disease will be the decisive factor. Since reactive hepatitis is not a viral species, antiviral drugs are not needed here. You will need medicines that increase immunity, B vitamins, hepatoprotectors and antioxidants.