Signs of liver inflammation in children. Prevalence of liver disease in children. Chronic hepatitis - liver disease in children

Liver diseases in children are hereditary and acquired, can manifest or occur at any age. In the first month of life, a child may develop symptoms of hepatomegaly - a moderate increase in the liver in children is a condition of the body, and not a disease. It passes by the age of two months, while pathological changes in the organ itself do not occur. In the first two weeks after birth, a newborn may have jaundice: this is normal and does not pose a threat to health.

Liver diseases such as:

It manifests itself as yellowing of the skin of the face, chest, abdomen from the chest to the navel and eye sclera, occurs in 50% of babies. It is important to prevent the transition from physiological to pathological, so that this does not lead to complications.

Infant jaundice occurs for natural reasons: due to the conflict between the Rh factor of the mother and the infant; mismatch of their blood groups (which is rare); premature birth, as a result of which the composition of the baby's blood changes more slowly.

When the child takes the first breath with light, a change in the composition of the blood occurs: in a premature baby, the body has not yet matured, and bilirubin is processed worse, its excess and leads to temporary staining of the skin and the whites of the eyes in yellow... At this time, the liver of a still weak child is overloaded, there is a risk of the transition from physiological jaundice to pathological.

With natural (neonatal) jaundice:

• the skin of the newborn acquires a yellow tint no earlier than 36 hours after birth;
• the level of bilirubin should decrease every day;
• the most intense yellowness becomes on the third day - after this time, the skin begins to lighten.

After 2 (maximum 4) weeks, the yellowness should go away completely. All this time, the child should be active, eat and sleep well.

Symptoms of pathological jaundice in a newborn:

• Yellowing of the skin a few hours after birth;
• Yellow skin on the arms, legs, feet, and palms;
• Frequent crying;
• Lethargy, constant sleepiness;
• Poor appetite up to refusal to eat;
• Dark colored urine;
• Colorless feces;
• Markedly enlarged liver
• The shade of yellow is not lemon, but greenish.

With these signs, you should immediately go to the hospital to measure and control the dynamics of the bilirubin level, undergo an ultrasound scan of the liver to detect damage to the bile ducts and a violation of the outflow of bile, and take liver tests for ALT and AST.

If the baby has physiological jaundice, glucose preparations, vitamins, herbal medicine are prescribed to him to support the body.

In order to reduce the level of bilirubin, phototherapy is recommended - staying for a certain time under the light of green and blue lamps... A nursing mother is prescribed a special diet food to reduce the fat content of milk so that a weakened baby does not have digestive problems.

In order to prevent pathological jaundice in infants, bilirubin is regularly measured in the first days of life, and parents should monitor the change in skin color in the child. In severe cases, surgery, blood transfusion and other procedures are prescribed in a hospital setting.

Hepatitis (jaundice)

If, against the background of yellowing of the skin, the child has manifestations unusual for physiological jaundice, this indicates a genetic pathology or the development of jaundice due to mechanical injuries received during the passage of the birth canal. A viral origin of the disease is also possible.

If pathological jaundice is not detected in a newborn child in time, this can lead to the penetration of bilirubin into the brain and the development of nuclear jaundice, the consequences of which are: damage to the central nervous system, delayed physical development, mental retardation. The child is probably losing coordination of movements. General intoxication of the body can be fatal.

Viral hepatitis

Transmitted to an infant from an infected mother during childbirth, an older child can pick up the virus during contact with a sick person. there is a chance of getting infected at the dentist, during vaccination in the clinic or surgical treatment in the hospital: the virus persists on poorly sterilized instruments.

Toxic hepatitis

It occurs as a result of an overdose of drugs, poisoning with household chemicals, food poisoning. In adolescent children, it can develop while drinking alcohol.

Autoimmune hepatitis

A pathology in which liver cells are destroyed by a person's own immune system. In an incompletely formed child's body, the progressive process of affecting one of the main hematopoietic organs occurs faster than in an adult. The liver tissue dies off and is replaced by scar tissue, leading to cirrhosis.

Fatty hepatitis

It occurs in children with obesity and pancreatic diseases. The liver tissues are reborn as a result of the accumulation of fat in them, the organ begins to function defectively.

Every third child preschool age sick with giardiasis. Children under 3 years of age tolerate the disease hard, since at this age, during infection, a high temperature rises, severe nausea, there is vomiting.

absorb nutrients from the blood, releasing toxins into it in return. The child's immunity decreases, he begins to feel weak, there is a lack of appetite. The weakened body becomes vulnerable to colds and inflammatory diseases, bronchial asthma and allergies can develop.

You can suspect giardiasis in a child by frequent oily, fetid stools.

Biliary obstruction

It is a blockage of the bile ducts. Infant baby it is almost impossible to cure with such a pathology - a liver transplant is necessary, the consequence of which can be cirrhosis. The reasons can be both congenital pathology and mechanical trauma during childbirth.

Tumor diseases

Oncological neoplasms in the liver tissues are very dangerous for children. This happens rarely, according to statistics. childhood cancer the liver accounts for only 4% of all cases of similar diseases in the population, but in 70% of cases of tumors in the liver tissues in children are malignant tumors. The most common cause is advanced hepatitis B and C.

Hepatic disorders

Almost all liver diseases in children have symptoms similar to various diseases gastrointestinal tract and other organs. If a child has risk factors for liver disease, then importance should be attached to the following symptoms:

• Jaundice of the skin and yellowness of the sclera;
• A constant subfebrile temperature from 37.1 ° C to 38 ° C without signs of colds and pains - this indicates sluggish latent inflammatory processes, which is characteristic of liver pathologies;
• Dark colored urine;
• Colorless feces;
• Nausea;
• Lack of appetite.

The child can feel heaviness in the right hypochondrium, bitterness in the mouth, becomes lethargic and physically unbearable, and experiences general malaise.

In children 5-7 years old, the biliary system is actively developing. In this regard, there may be moderate hepatomegaly - a small but palpable enlargement of the liver. The child may experience mild ailments, the skin may turn yellow. This is due to age-related physiology, and does not speak of a disease. There is no need for any treatment, but the diet shown for liver diseases in children will not be superfluous.

Treatment and prevention

Treatment of liver diseases in children is conservative and surgical. Prescribed for inflammation - antibiotics; with hepatitis, cirrhosis - hepatoprotectors; v necessary cases – choleretic drugs... Laparoscopy is performed - a bloodless operation, if necessary - an abdominal one.

Preventive measures are aimed at maintaining the immunity of the growing child's body and the formation of tissues. The menu should contain vegetables, herbs, fruits, dairy products - cottage cheese, yoghurts. Meals should be complete, the child should follow the meal regimen - breakfast, lunch and dinner should be on time.

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Terminology

Hepatomegaly: significant enlargement of the liver.
Jaundice: yellow staining of the mucous membranes, sclera and skin caused by the deposition of bile pigments in them.
Cholestasis: a violation of the movement of bile in the form of stagnation in the bile ducts and / or ducts.
Hepatitis: inflammation of the liver:

1. acute - lasting no more than 3 months;
2. chronic lasting more than 3 months;
3. congenital (synonym - fetal) - the general name of hepatitis that occurs with intrauterine damage to the liver of the fetus under the influence of various factors inducing inflammation;
4. infectious (synonym - Botkin's disease, epidemic, hepatitis A) - of a viral nature, characterized mainly by the fecal-oral route of infection, incubation period lasting 3-6 weeks, more often acute onset with an increase in body temperature;
5. active (synonyms - aggressive, chronic active) - chronic hepatitis, characterized by frequent exacerbations, pronounced portal, periportal and intralobular infiltration; transition to cirrhosis of the liver is possible;
6. persistent (synonym - chronic persistent) - chronic hepatitis, characterized mainly by mild infiltrative processes in the liver, benign course with rare exacerbations and long periods of remission, wear clinical picture, preserving the possibility of restoring the morphological structure of the liver;
7. reactive (synonym - satellite, concomitant) - hepatitis resulting from damage to other internal organs.

Liver cirrhosis: a chronic, progressive disease characterized by dystrophy and necrosis of the hepatic parenchyma, accompanied by its nodular regeneration, diffuse proliferation of connective tissue and deep restructuring of the liver architectonics.

Classification

To date, we do not have a generally accepted classification of liver disease in children, which is due to the variety of their clinical forms and syndromes, the lack of a common understanding of the etiopathogenesis of many of them, as well as a single concept of its construction. In this chapter, the reader will be able to familiarize himself with different options classifications based on syndromic, pathogenetic, or nosological principles. We deliberately cite both those and others below, although we are convinced that classifications of a nosological nature should be considered methodologically more important. Syndromic classifications are predominantly of screening value, followed by a mandatory access to a clinical diagnosis. Even MS Maslov (1951) pointed out: "The name" jaundice "should be removed from the terminology, because jaundice is only a symptom ... In addition, there is no doubt the existence of liver suffering, where the symptom of jaundice is not revealed at all."
Two clinical symptoms are considered most characteristic of liver disease in children, namely jaundice and hepatomegaly. They are the pivotal ones in the construction of classifications of liver diseases based on the syndromic principle. As can be seen from these classifications, both jaundice and an enlarged liver can be observed in diseases of various organs and systems of the child's body, and not just the liver itself, which should be taken into account when carrying out differential diagnosis... Jaundice and (or) hepatomegaly, being integrative signs of the disease, are an external expression of complex pathological processes occurring in one or another link of the biological system available for physical assessment.

Liver disease with jaundice

Newborns and infants

Infections (congenital and acquired):

Metabolic disorders:

1. hereditary - ai-antitrypsin deficiency, galactosemia, hereditary fructose intolerance, cystic fibrosis, tyrosinosis, Niemann-Pick disease;
2. acquired - cholestasis and liver damage associated with completely parenteral nutrition, severe erythroblastosis;
3. idiopathic disorders - neonatal hepatitis (giant cell hepatitis), familial liver cirrhosis, hereditary lymphostasis with cholestasis.

Anomalies in the structure of the bile ducts:

1. atresia and hypoplasia - atresia of the extrahepatic biliary tract, hypoplasia of the intrahepatic biliary tract, hepatic artery dysplasia;
2. cysts - cyst of the common bile duct, cystic enlargement of the main intrahepatic ducts (Caroli disease), congenital liver fibrosis, polycystic liver and kidney disease.

Children and adolescents

Scheme 1. Differential diagnostic algorithm for neonatal jaundice

Table 1.
Clinical forms of neonatal jaundice

Genesis of jaundice (according to the time of action of the factor)	Excess factions bilirubin	Defect level in the exchange of bilirubin	A type (on patho- genetic mechanism)	Time mani- festivals	Severity		Complications
Congenital	Free	Suprahepatic	Hemolytic	1st day	Moderate	Fast and slow progressing	Bilirubin encephalopathy
Acquired	Related	Hepatic	Transport "Capture"	On the 2-3rd day		Stable	Biliary cirrhosis (fibrosis) of the liver
Idiopathic		Sub-hepatic	Conjugation	After the 3rd day	Sharp expressed	Transient
		Mixed	Excretory			With periodic rises
			Mechanical "Thickening"	On the 10-14th day		Regressive
			Enterohepatitis

* If possible, indicate the shade of jaundice: lemon, orange, greenish, etc.

Classification of jaundice of newborns

Hereditary	Acquired
I. Hemolytic
Erythrocyte membranopathies Erythrocyte enzymopathies Hemoglobinopathies	Hemolytic disease of the newborn Hemorrhages (hematomas) Polycythemia, polyglobulia Medicinal hemolysis
II. Hepatic
Seizure disorder B (Gilbert's syndrome) Conjugation disorder B (Crigler-Najar syndrome type I and II) Impaired excretion of B (Dabin-Johnson, Rotor syndromes) Symptomatic (with hypothyroidism, galactosemia, fructosemia, tyrosinosis, Niemann-Pick disease, etc.)	Infectious hepatitis Toxic and metabolic hepatosis Jaundice from breast milk Conjugation disorder B in pyloric stenosis Iatrogenic conjugation disorder
III. Mechanical
Syndromic anomalies of the biliary tract Familial cholestasis Deficiency of a - antitrypsin, cystic fibrosis	Syndrome of thickening of bile Atresia of the biliary tract with inflammation and (or) hepatitis Paresis and other types of intestinal obstruction Compression from outside the biliary tract
IV. Mixed genesis
	Transient jaundice of newborns (physiological) Preterm jaundice With intrauterine infections With disseminated intravascular coagulation

At the heart of jaundice, including the neonatal period, are most often violations of pigment, bilirubin metabolism, in connection with which we briefly recall its main stages.

The main source of bilirubin (B) is hemoglobin metabolites formed from senescent erythrocytes in the cells of the reticuloendothelial system. B (free, indirect, unconjugated) is released into the blood, where it binds to its proteins and is transported to the liver. About 5-20% of B is formed in hepatocytes from other heme-containing substances. The capture of B by hepatocytes, its conjugation and release into the bile capillaries are active processes in which various enzymes are involved. In particular, in the endoplasmic reticulum of hepatocytes with the participation of the enzyme glucuronyltransferase, B is conjugated with glucuronic acid to form glucuronides B (bound, direct, conjugated B), which are water-soluble and non-toxic compounds. Through the biliary pole of the hepatocyte, conjugated B is excreted into the bile capillaries, and then with bile into the intestine. Two transport proteins B (Y and Z) have been isolated. Both of them are involved in the transfer of B from the blood capillary through the hepatocyte to the bile capillary, and only one of them (Z), being present both in the liver and in the intestine, is in the enterohepatic cycle of B. The main factor of B uptake from the blood and its carrier is in hepatocyte protein Y is considered. In newborns, especially in premature babies, on the one hand, there is an insufficient synthesis of the transport protein Y, on the other, underdevelopment of glucuronyl transferase activity. This is regarded as the main causes of transient hyperbilirubinemia ("physiological jaundice") in newborns. Thus, "physiological jaundice" is essentially conjugational, that is, caused by the accumulation of indirect B in the blood due to its inadequate translation into a straight line.
In pediatric practice, the most widespread are information about conjugative jaundice caused by hereditary defects in the glucuronyltransferase system (hereditary pigmentary hepatosis) - Gilbert's syndrome, Crigler-Najar, Dabin-Johnson, Rotor. At the same time, variants of jaundice, primarily of the neonatal period, caused by impaired conjugation and transport of free B under the influence of non-heritable causes (hypoxia, endocrine factors, drug therapy, other). This is reflected in the corresponding classifications based on the pathogenetic principle.
Of clinical interest is jaundice, the least known to medical practitioners, in 1% of breastfed babies. The cause of jaundice is the steroid pregnan-3, 20-diol found in breast milk, which competes with B for glucuronyl transferase, thereby disrupting the process of conjugation of the latter. According to another hypothesis, increased content in breast milk fatty acids and, possibly, protein lipase causes the attachment of free B to the transport protein, and thus the capture and conjugation of B by hepatocytes. Jaundice with this variant of hyperbilirubinemia appears between the 6th and 8th days of life in a healthy child and gradually decreases after the cessation of breastfeeding or after several weeks against the background of continued natural feeding. Due to the possibility of developing neurological complications of hyperbilirubinemia, it is advisable to temporarily (for 7-10 days) replace breast milk with adapted milk formulas. In the future, when returning to natural feeding, hyperbilirubinemia does not recur.

The estimated prevalence of neonatal liver disease is 1 in 2,500 live births.

Early recognition is especially important in Newborns and Infants, as a delay in diagnosis can cause Negative influence on the forecast.

It is clearly recognized that if biliary atresia is diagnosed after 2 months of age, the success rate of surgical correction (hepatoportoenterostomy) is sharply reduced.

Moreover, as liver dysfunction progresses, early recognition makes possible more successful nutritional support for the patient and a potential delay in the decline. hepatic function... The result can be improved growth and fewer side effects.

It has great importance because orthotopic liver transplantation is usually more successful in infants weighing more than 10 kg at the time of surgery (liver transplantation is a reality for a pediatric patient with severe liver disease).

Unfortunately, early recognition of severe liver disease in a pediatric patient remains a major challenge. One of the factors contributing to this is that the lesion of the liver of a pediatric patient has a limited number of manifestations.

Consequently, various disorders often have virtually identical initial manifestations.

For example, newborns with liver damage almost always present with jaundice. Unfortunately, the difference between "physiological hyperbilirubinemia" and hyperbilirubinemia, indicating severe liver damage, is often underestimated. Data from the United Kingdom have documented a number of factors contributing to the late referral of children with liver disease (Table 1).

Table 1
Reasons for the delay in referral to a specialist for children with liver disease

Lack of follow-up of neonatal jaundice (including inability to fractionate serum bilirubin) Inadequate investigation of hemorrhagic disease / coagulopathy Misdiagnosis of cholestasis (conjugated bilirubinemia) as jaundice caused by breast milk(unconjugated bilirubinemia) False confidence caused by decreased bilirubin concentrations or pigmented stools

ETIOLOGY

The causes of liver disease in pediatric patients vary by age (Table 2).

Table 2.
The most common causes of liver disease in children of different ages

NEWBORNS AND INFANTS

Cholestatic disorders - Biliary atresia - Common bile duct cyst - Insufficiency of intrahepatic bile ducts (e.g. Allagile syndrome) - Progressive familial intrahepatic cholestasis syndromes (Byler disease and syndrome) - Benign recurrent intrahepatic cholestasis (Caroli's disease and syndrome) disease) - Cholelithiasis

Idiopathic neonatal hepatitis and mimicking diseases- Cystic fibrosis - Alpha-1-antitrypsin deficiency - Hypopituitarism / hypothyroidism - Neonatal iron storage disease

Viral hepatitis and other infectious diseases of the newborn- Cytomegalovirus - Herpes simplex / human herpes virus 6 / - Epstein - Barr virus - Parvovirus B19 - Rubella - Reovrus - type 3 - Adenovirus - Enterovirus - Syphilis - Tuberculosis - Toxoplasmosis

Metabolic disease- Disorders of peroxysmal function (Zellweger syndrome) - Disorders of bile acid metabolism - Disorders of the urea cycle (arginase deficiency) - Disorders of amino acid metabolism (tyrosinemia) - Disorders of lipid metabolism (Niemann-Pick type C / Gaucher / Wolman) - Disorders of carbohydrate metabolism (galactosemia, fructosemia, glycogen storage disease type IV)

Toxic / pharmacological damage (e.g. acetaminophen (paracetamol), total parenteral nutrition, hypervitaminosis A)

Tumors (intra- and extrahepatic)

Moreover, although "neonatal hepatitis" can be caused by viruses, it is not the same entity as viral hepatitis seen in older children and adolescents.

Although the lists various reasons leading to liver disease in children is extremely long, about 10 diseases account for approximately 95% of all cases of observed cholestasis, and of these, biliary atresia and neonatal hepatitis are responsible for more than 60%.

Typically, the clinician first suspects liver disease in the newborn who presents with classic features such as persistent jaundice, hepatomegaly, coagulopathy, or weight loss.
In other cases, it is the accidental detection of abnormalities in serum testing.
Jaundice, confusion, and coma have been reported in older children and adolescents with acute hepatitis or after exposure to a toxin. Pruritus seen in older children can be considered irritability in infants.

ANAMNESIS AND SIGNS OF LIVER DISEASE

Newborn

Although the infant may have had jaundice at birth (physiologic hyperbilirubinemia) or is breastfeeding, it is important not to attribute jaundice to a baby over 14 days old due to one of these causes.

Jaundice in any child over 2 weeks of age should raise suspicion of liver disease and prompt an appropriate assessment.

A careful history can provide clues as to the existence and type of liver disease.

For example, the onset of liver disease associated with dietary changes may raise the suspicion of a congenital malfunction of carbohydrate metabolism, such as an inability to metabolize galactose or fructose.

A positive family history of a suspected genetic disorder should focus the initial assessment in this direction. A recurrent clinical phenotype within a family suggests an inherited disorder such as tyrosinemia or Byler syndrome (progressive familial idiopathic cholestasis).

Idiopathic neonatal hepatitis is more common in boys, especially preterm and low birth weight infants.

In contrast, biliary atresia occurs more frequently in girls of normal weight, and the rate of intrafamilial recurrence approaches zero. Also, the concomitant polysplenia syndrome speaks in favor of the diagnosis of biliary atresia.

Patients with biliary atresia have earlier onset of jaundice and the appearance of acholic stools than those with neonatal hepatitis.

In cholestatic disease, jaundice is almost invariably noted in the first month of life.

Aholic stools are also highly characteristic of cholestasis in infancy. In the presence of extra or intrahepatic obstruction, little or no bilirubin is secreted into the intestine, leading to a lack of color in unformed fecal material.

Although some pigment may be present in the stool of newborns with biliary obstruction due to desquamation of pigmented cells into the stool.

Moreover, the disintegration of the stool into pieces usually indicates that the pigment is only superficial, while it interior is clay-colored at best.

Maternal fever or other signs of infection raise the suspicion of sepsis as the underlying cause of neonatal jaundice. Gram negative bacteria (e.g. E coli) causing infection urinary tract infections are especially common.

Older child

In older children with a history of anorexia. fever, vomiting, abdominal pain, and dark urine should lead to suspicion of hepatitis A virus (HAV) infection.
HAV infection is also a likely etiology of liver disease in any child with a history of influenza-like illness who suddenly develops jaundice with elevated aminotransferase readings in the absence of any known exposure to hepatotoxic agents. Hepatitis A is often anicteric infection in children younger than 5 years of age and is often unrecognized.

Signs of liver disease in patients who have received tattoos, who have used intravenous drugs, or whose medical condition has resulted in increased exposure to parenteral blood products (hemodialysis, hemophilia, surgery) prior to widespread screening (1992) may raise suspicion of infection hepatitis C.
Adolescents who develop jaundice should be asked confidentially about intravenous drug use, exposure to pure cocaine, intranasal use, which may be associated with hepatitis C (and possibly hepatitis B) infection.

If the course of confirmed hepatitis B infection is particularly severe, concurrent infection or superinfection with hepatitis (D) delta should be suspected.

It is always important to ascertain exposure data to potentially hepatotoxic drugs, including isonazid, nitrofurantoin, sulfonamides, and nonsteroidal anti-inflammatory drugs such as acetaminophen and ibuprofen.

If an overdose or intoxication is the cause of liver dysfunction, children may have an altered mental status and even coma.

Confusion and coma raise suspicion of liver failure or metabolic disease resulting in hyperammonemia, hypoglycemia, and a combination of both.
Adolescent girls who develop jaundice and have a history of acne, intermittent arthritis and fatigue, possibly with autoimmune hepatitis; this nosological unit is less common in boys and younger children.

Patients with immunodeficiency and jaundice may suffer from cytomegalovirus, Epstein-Barr virus or retrovirus infections.

A history of pharyngitis in a patient who also has jaundice, splenomegaly, and lymphadenopathy suggests Epstein-Barr virus infection.

Colic in the upper right quadrant and a history of nausea (especially after eating a fatty meal) indicate gallbladder disease, which is more common in older children.

Consideration should be given to the signs and symptoms of obesity, heart, endocrine, or intestinal disease, as abnormalities in serum aminotransferase may reflect secondary liver damage in systemic disease (liver as an "innocent bystander").
An increase in the concentration of aminotransferases (especially AST) can also be a manifestation muscle disease.

Older children and adolescents with liver disease may initially complain of anorexia, fatigue, and yellow sclera.

Cholestasis can lead to complaints such as pruritis and especially dark and frothy urine. This color is due to choluria (bile pigment in the urine); the presence of foam suggests choleuria (bile salts in the urine).

Bile salts are detergent molecules that lower the surface tension of solutions, thus creating visible foam.

PHYSICAL MANIFESTATIONS

Common physical manifestations associated with specific liver disease are listed in Tables 3-6.

Table 3.
Diseases Causing Jaundice / Elevated Liver Enzymes

BABIES
Infection- Bacterial sepsis (E coli) - Viral infections: cytomegalovirus, rubella, Coxsackievirus, echovirus, herpesvirus, adenovirus. -Metabolic disorders -Hereditary: alpha 1-antitrypsin deficiency, galactosemia, hereditary fructose intolerance, cystic fibrosis, Niemann's disease -Pick, tyrosinemia -Acquired: cholestasis and liver disease caused by general parenteral nutrition, hypothyroidism, panhypopituitarism progressive familial intrahepatic cholestasis (e.g. Byler disease), Ivemark syndrome, cerebrohepatorenal (Zellweger) syndrome

Malformations of bile streams

Non-syndromic and syndromic atresia / insufficiency of intrahepatic bile ducts (Allagile syndrome) - Cystic malformations: common bile duct cysts, cystic enlargement of intrahepatic bile ducts (Caroli disease), congenital hepatic fibrosis, polycystic liver and kidney disease.

CHILDREN OVER AGE AND AGE

Acute viral hepatitis (HAV)

Hereditary diseases:

Wilson disease, cystic fibrosis, hepatic porphyria, Dubin-Johnson syndrome, Rotor syndrome

Malignant diseases:

Leukemia, lymphoma, liver tumors

Chemical substances:

Hepatotoxic drugs, toxins (hydrocarbon intestines, alcohol, organophosphates, hypervitaminosis A, mushrooms, acetaminophen). schistosomiasis, leptospirosis, visceral larva migrans

Idiopathic or secondary lesions: chronic hepatitis, inflammatory bowel disease (ulcerative colitis), rheumatoid arthritis, obesity.

Among this profusion of physical manifestations, the most common are hepatomegaly and jaundice.

Hepatomegaly is often the only manifestation of liver disease, although palpation of the liver edge can be misleading due to variations in contour norm, body habitus, or displacement of the liver edge by adjacent organs or external or internal neoplasms.

Hence, liver width measurement is a useful adjunct to palpation during initial presentation and follow-up.
Liver width - the distance between the edge of the liver and upper bound dullness, determined by percussion at the right midclavicular line. The average width varies from 4.5 cm at 1 week of age to 6-7 cm in early adolescence.

Normally, the liver is round and soft, and the surface is smooth. A hard, thin edge and nodular surface may suggest fibrosis or cirrhosis.
The latter condition is also often associated with a small liver.

Palpation of the liver in the epigastric region indicates either cirrhosis or a Riedel lobe (normal anatomical lengthening of the right lobe, which can be mistaken for hepatomegaly).

Table 4.
Diseases causing hepatomegal

BABIES AND CHILDREN
Accumulation diseases

Acute: Reye's syndrome (fat) - Chronic: glycogenoses, mucopolysaccharidoses, Gaucher's disease, Niemann-Pick disease, gangliodidosis, Wolman's disease - Nutritional problems: total parenteral nutrition (calorie overload, kwashiorkor, diabetes) - Infiltrative disorders: leukemia, lymphoma, Langerhans cell histiocytosis, granulomas (sarcoidosis, tuberculosis) Congenital hepatic fibrosis

Tumors

Primary: hepatoblastomas, hematoma, hemangioendothelioma - metastatic: neuroblastoma, Wilms tumor, gonadal tumors.

Table 5.
Diseases Causing Liver Failure

NEWBORNS AND INFANTS

Infections:

Herpesviruses, echo, adenoviruses, sepsis.
Metabolic disorders: hereditary fructose intolerance, mitochondrial diseases, tyrosinemia, galactosemia, nonatal iron storage disease.
Ischemia / shock:
Drugs / Toxins: valproate, acetaminophen

CHILDREN AND ADOLESCENTS
Infections: herpes viruses, echo, adenoviruses, sepsis
Drugs / Toxins: valproate, acetaminophen, mushrooms (Amanita)
Malignant disease
Ischemia / shock: congenital heart disease, myocarditis, severe hypotension.
Metabolic: Wilson's disease, fatty liver infiltration during pregnancy.

Table 6.
Various physical manifestations associated with liver disease

BABIES
Microcephaly: congenital cytomegalovirus, rubella, toxoplasmosis
Typical face type: arneriohepatic dysplasia (Allagile syndrome)
Cataract: galactosemia
Retinal pigmentation: Allagille syndrome
Abnormal manifestations during lung ascultation: cystic fibrosis.
Neuromuscular disorders (tremors, lethargy): lipid storage disease, Wilson's disease, oxidative phosphorylation disorders

CHILDREN
Prurite: chronic cholestasis
Hemangiomas: liver hemangiomatosis
Kayser-Fleischer Rings: Wilson's disease
Glossitis: cirrhosis

Kidney enlargement: congenital hepatic fibrosis or polycystic disease
Arthritis and erythema nodosum: liver disease with chronic inflammatory bowel disease. acne, fatigue: autoimmune hepatitis.

Palpation of the abdomen can also reveal an enlarged spleen, which is usually of normal size early in the course of liver disease.

If the spleen is enlarged, one of the many causes of portal hypertension or storage disease should be suspected.
Pain on palpation with hepatomegaly may simply reflect a mild viral stroke with enlargement of the Glisson capsule due to edema, which is responsible for perceived pain localized to the liver.

Severe hepatosplenomegaly indicates storage disease or malignant disease, although particularly dramatic hepatomegaly itself is associated with severe hepatic fibrosis

In this condition, the kidney must be evaluated to rule out coexisting autosomal recessive or dominant polycystic kidney disease.

Auscultation of the liver may allow the clinician to detect vascular bruising caused by anatomical vascular malformations or increased blood flow to the liver.

Ascites suggests increased portal venous pressure and impaired hepatic function.

Certain physical signs raise significant suspicion of specific liver disease. In newborns who suffer from congenital infection, comorbidities often include microcephaly, chorioretinitis, purpura, low birth weight, and generalized organ failure.

Dysmorphic traits can be characteristic of certain chromosomal abnormalities. Patients with Alagille syndrome usually have a characteristic face type (coracoid nose, high forehead, butterfly-shaped vertebrae and murmur on cardiovascular auscultation due to peripheral pulmonary stenosis and posterior embryotoxin on ophthalmologic examination.

The presence of intermittent vomiting in a newborn, especially unrelenting vomiting, may indicate a congenital metabolic disorder, which is usually also associated with poor nutritional status and irritability. The onset of symptoms (such as vomiting) after the introduction of a new product containing galactose or fructose could raise suspicion of galactosemia or hereditary fructose intolerance.

Congenital ascites may suggest liver failure, cirrhosis, or storage disease.
Children with cholestasis often suffer from intense pruritis, which is characteristic of obstructive liver disease, which is primarily manifested by irritability.

LABORATORY ASSESSMENT

Types of liver damage
Laboratory manifestations of liver damage can be divided into 2 types:
1) cholestatic or obstructive lesion of the bile ducts and
2) hepatocellular damage or damage to liver cells.
However, there is often significant overlap between the types of damage in a patient with liver disease.

Cholestasis is characterized by the accumulation of compounds that cannot be excreted due to occlusion or obstruction of the biliary tree. Hence, serum concentrations of substances (bile pigments, enzymes, bile salts) that are normally present in bile or are removed through bile usually increase in cholestatic conditions. Alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and conjugated bilirubin (all require pure biliary tree for elimination) are usually elevated.

Conversely, hepatocyte necrosis after viral or toxic liver stroke (eg, acetaminophen overdose or viral hepatitis) usually causes primarily an increase in enzymes contained within the hepatocyte, such as aminotransferases (ALT and AST). In hepatocellular disease, serum GGT and AP levels still do not rise to the same extent as aminotransferases. This distinction between the two main types of liver damage is not always clear-cut.

For example, cholestasis invariably leads to some degree of hepatocellular dysfunction due to the toxic accumulation of bile within the hepatocytes and biliary tree. In hepatocellular disease, decreased bile blood flow (sludge) that results from hepatocyte necrosis also causes a mild increase in serum obstruction markers (AP, GGT).

The two main types of liver disease can be differentiated early on. painful process but most often, the underlying type of liver disease is diagnosed by interpreting a combination of clinical and laboratory criteria, including liver biopsy. This is especially true for newborns and infants, who show the greatest overlap between types of liver damage. It is most important to recognize the presence of cholestasis in patients in this age group, even in premature infants who have jaundice after 14 days of life requiring evaluation. Table 7 shows the objectives of the stepwise assessment of infants with jaundice.

Table 7.
Objectives for the stepwise assessment of infants with jaundice
Recognize cholestasis (unconjugated or physiologic hyperbilirubinemia)
Assess the severity of liver damage
Separate specific entities (e.g. metabolic versus viral versus anatomical)
Differentiate biliary atresia from idiopathic neonatal hepatitis
Differentiate idiopathic neonatal hepatitis from progressive familial intrahepatic cholestasis and bile duct insufficiency.

Table 8 lists our recommendations for data collection when evaluating an infant with suspected cholestasis. An accelerated assessment is proposed for infants who present at 2 months of age with cholestasis to rapidly rule out biliary atresia.

Table 8.
Stepwise assessment of infants with suspected cholestatic liver disease

Confirm cholestasis
- Clinical evaluation (family history, feeding history, physical examination)
- Fractionation of serum bilirubin and determination of serum bile acid levels
- Evaluation of stool color
- Index of hepatic synthetic function (time of prothrombin and albumin)

Recognize specific nosological units
- Viral and bacterial cultures (blood, urine, cerebrospinal fluid)
- Hepatitis B surface antigen and other viral and syphilis titers (VDRL) in selected at-risk patients
- Metabolic screening (urine reducing substances, urine and serum amino acids.)
-Thyroxine and thyroid-stimulating hormone
- Alpha 1-antitrispin phenotype
- Sweat chlorides
- Qualitative analysis of urine bile acid profile
- Ultrasonography

Differentiate biliary atresia from neonatal hepatitis
- Hepatobiliary scintigraphy or duodenal intubation for bilirubin
- Liver biopsy

Liver function tests

Since the liver has a large functional reserve, abnormal laboratory parameters are often the only manifestation of overt hepatic disease and can be noted long before overt clinical manifestations. In the usual scenario, a doctor who suspects liver disease will usually order "Liver function tests" (LFT) to evaluate liver function. By consistently monitoring these indicators, information about the prognosis, response to therapy and the degree of dysfunction can be provided.

However, the term LFT is not entirely accurate, as only two of the commonly reported parameters are true indicators of hepatic function - prothrombin time (PT) and serum albumin levels - both of which measure synthetic ability. All of the other parameters are essentially indirect measures of hepatic function, and many of these parameters change in situations other than liver disease. For example, elevations in aspartate aminotransferase (AST) accompany hemolysis of red blood cells, muscle breakdown, and pancreatic disease.

Biochemical abnormalities associated with liver disease are not limited to LFT abnormalities. For example, nonketotic hypoglycemia suggests a defect in fatty acid beta-oxidation and ketone production. Severe ketosis - a rare finding in infants - may indicate organic acidemia, glycogen storage disease, or a deficiency in neurogenesis. An increase in anion shift in metabolic acidosis also suggests organic acidemia. Hypo- and hyperthyroidism can be associated with jaundice. Sweat chloride determination may be required to rule out cystic fibrosis. Iron and ferritin tests are helpful in diagnosing neonatal iron storage disease. Determination of bile acid levels in urine and serum usually helps to rule out the possibility of congenital disorders of bile acid metabolism. Urinary succinylacetone levels may indicate the presence of tyrosinemia. A urine sample and culture should always be obtained from any child with jaundice, as urosepsis is usually associated with conjugated hyperbilirubinemia (eg, E coli urinary tract infection). Anemia and hemolysis may indicate the presence of a hemolytic condition responsible for jaundice (usually unconjugated) and may not be associated with liver disease.

Of all the laboratory research fractionation of bilirubin is most important.
A healthy mature liver removes unconjugated bilirubin from the blood and mediates the conjugation of unconjugated bilirubin by two glucuronic acid molecules. Bilirubin conjugation converts an essentially fat-soluble substance (unconjugated bilirubin) into a water-soluble substance (conjugated bilirubin) that can be secreted into bile, an aqueous medium. It is the fat-soluble nature of unconjugated bilirubin that allows it to cross the blood-brain barrier and potentially cause kernicterus.

Physiologic neonatal jaundice (in which levels of unconjugated bilirubin increase) results from an immaturity of the glucuronyl transferase system responsible for conjugating bilirubin. Jaundice associated with breastfeeding (slight temporary delay in conjugating ability) is usually the result of ingredients in breast milk.

In unconjugated bilirubinemia, serious liver disease is unlikely, but the child may need to be evaluated for possible hemolysis, congenital disorders of bilirubin metabolism (eg, Crigler-Najar types 1 and II), and dysfunction thyroid gland... Extreme unconjugated hyperbilirubinemia may be associated with neonatal kernicterus.
In the presence of conjugated (direct, bound) bilirubin, the evaluation should be aggressive. A serum conjugated bilirubin reading greater than 17 mcmol / L (1 mg / dL) or greater than 15% of the total bilirubin reading should be considered abnormal and evaluated immediately! Unconjugated bilirubin levels reflect excess bilirubin production (eg, as a result of hemolysis) or a delayed liver's ability to bind bilirubin. The conjugated fraction is associated with serious liver disease and indicates cholestasis.

Analysis of urine
Urobilinogen is formed as a result of the degradation of conjugated bilirubin by bacteria present in the intestinal lumen, and is also found in urine. Most of the urobilinogen is excreted in the stool as coprobilinogen; 20% undergoes enterohepatic recirculation. Only a small fraction enters the urine, but it increases in the presence of hepatocellular damage due to decreased liver uptake and recirculation. Undoubtedly, urinary urobilinogen is almost absent in the presence of an obstructive process, since less bilirubin enters the intestine and less is converted to urobilinogen. Interestingly, delta-bilirubin, due to its covalent binding to albumin, is not excreted in the urine, and therefore tends to remain elevated in serum for some time after initially cholestatic stroke, since its disappearance depends on the breakdown of albumin. -bilirubin complex.

Aminotransferase activity
Alanine aminotransferrase (ALT) levels (formerly known as serum glutamic pyruvate transferase - SGPT) and AST (formerly known as serum glutamic oxaloacetic transaminase-SGOT) are the most sensitive assays for hepatocyte necrolysis. A significant increase in these enzymes, which are released from damaged hepatocytes, indicate hepatocellular damage. Slightly disturbed levels can also be associated with cholestatic processes, since the backflow or stasis of bile is toxic to hepatocytes. These enzymes catabolize the reversible transition of the alpha-amino group of the amino acids alanine and aspartic acid into the alpha-keto group of ketoglutaric acid, which leads to the formation of pyro-tartaric acid (ALT) and oxalic-acetic acid (AST).

ALT is more specific for liver disease because it is found only in low concentrations in other tissues (eg, muscle). In contrast, AST is found in high concentrations in many tissues, including heart and skeletal muscle, kidney, pancreas, and red blood cells. The coenzyme of both enzymes is vitamin B6, so persistently abnormally low AST and ALT values ​​suggest an underlying vitamin B6 deficiency.

In general, aminotransferase readings still do not provide information regarding specific diagnoses, but particularly high levels suggest drug hepatotoxicity (eg, acetaminophen overdose), hypoxia / shock, and viral hepatitis. These levels still have no predictive value; patients with very high abnormalities may feel good, especially in the case of acetaminophen toxicity. However, they are useful in monitoring a patient's clinical progress, for example, progressively declining AST / ALT scores in a young patient who has HAV infection and who is otherwise doing well is a reassuring sign that the liver disease is resolving. Conversely, declining AST / ALT values ​​in the presence of a wrinkled liver, an increasing PT of partial thromboplastin time (PTT), and in the absence of clinical improvement are an ominous sign. This suggests a reduced functioning hepatocyte mass due to necrosis, which has reduced the amount of enzymes available for release into the circulation.

Alkaline Phosphatase (AP) Levels
AP is localized primarily in the tubular membrane of the liver cells, therefore, an elevated serum AR level usually indicates obstructive liver disease (eg, bile duct obstruction). However, AR is found in other tissues, including bone, kidney, and small intestine. High rates of AR are usually found in children during periods of accelerated growth, such as surges in puberty. Especially high levels should lead to suspicion of possible bone pathology (eg, rickets), especially if an increase in AR is not associated with an increase in GGT. If levels of the latter enzyme are also elevated, bone disease is unlikely. This simple observation reduces the need to fractionate the AP value into individual isoenzymes to determine the exact source of their increase. For example, zinc-coenzyme-AP - persistently low AP levels may indicate low serum zinc levels.

Serum and urine bile acids
The production and transport process that takes place in the liver (bile acid synthesis, conjugation and secretion) maintains cholesterol levels, facilitates bile flow and provides surface active detergent molecules that promote intestinal lipid absorption. The proper functioning of this system promotes a balance between the absorption of bile acids from the intestine and their uptake by hepatocytes. With no changes ileum(eg, short bowel, Crohn's disease) Serum bile acid levels are a reliable indicator of the integrity of the enterohepatic circulation.

Although serum bile acids do not provide specific information about the type of liver disease present, they are elevated in patients with either acute or chronic liver disease in whom bilirubin levels may still be normal. Changes in serum bile acid levels can be not only quantitative but also qualitative. In certain diseases, "atypical" bile acids such as lithocholic acid accumulate instead of the normal cholic and chenodeoxycholic acids. Interpretation of elevated serum bile acid levels in newborns and infants is complicated by the presence of relative "physiological cholestasis", which can lead to elevated serum bile acid levels even in healthy infants. However, specific defects in bile acid metabolism are associated with cholestasis, either due to insufficient production of normal trophic and choleretic bile acids, or excessive production of hepatotoxic bile acids. Accurate identification of precursors of metabolites makes it possible to determine specific congenital disorders of bile acid metabolism. With the help of recent technological advances such as fast atom bombardmnet - mass spectrometry (fast atomic bombardment mass spectrometry), it is possible to quickly analyze urine samples from individuals with suspected specific bile acid disorders and to determine specific congenital disorders of bile acid metabolism, such as 3 β-hydroxysteroid dehydrogenase / isomerase and delta-4-3-oxosteroid-5-β reductase deficiency, which manifest as severe liver disease.

Gamma Glutamyl Transferase (GGT)
GGT - contained in the epithelium of the small bile duct, as well as inside hepatocytes; in the pancreas, spleen, brain, mammary glands, small intestine and especially in the kidneys. Therefore, an increase in serum GGT does not specifically indicate liver disease.

Since GGT levels are still not elevated in individuals with bone or intestinal abnormalities, this finding is particularly useful in identifying the origin of elevated AR levels. GGT values ​​(like AR) change with age, the laboratory should use age-appropriate reference values. For example, an apparently high GGT level in a newborn may not be abnormal; similar indicators in this age group are usually up to 8 times higher than those observed in adults. Finally, GGT scores may be elevated in response to various pharmacological modalities such as anticonvulsants, so the clinician needs to be aware of the patient's recent exposure to drugs.

Albumen
A decrease in serum levels of albumin, which is synthesized in the uneven endoplasmic reticulum of healthy hepatocytes, may suggest decreased production due to decreased hepatic function after hepatocellular disease. But, low concentration albumin - late onset in liver disease. When present, it raises suspicion of a chronic illness. Undoubtedly, the sharp decrease in albumin in a patient with long-term illness is of particular concern, although such a decrease in patients with ascites may simply reflect a change in the total volume of distribution.

Ammonia
The production of ammonia occurs as a result of the action of bacteria in the colon on proteins in the diet, and the liver plays a major role in the elimination of ammonia. Undoubtedly, a poorly functioning liver still does not catabolize ammonia. Hyperammonemia and encephalopathy are classic manifestations of liver failure, and there is a labile correlation between encephalopathy and serum ammonia levels (unless the sample is obtained in a fasting state and quickly transported to the laboratory on ice, dramatically increased ammonia levels can be obtained).

Prothrombin Time (PT)
The production of coagulation factors II, VII, IX and X depends on an adequate intake of vitamin K (individuals with malnutrition are at risk). Because it is a fat-soluble vitamin, vitamin K deficiency is common in people with obstructive liver disease, in whom bile acids do not reach the intestines. Therefore, PT, the time required for prothrombin (factor II) to convert to thrombin, is usually elevated in the presence of biliary obstruction. RT can also be elevated in the presence of true hepatocellular disease, a poorly functioning liver cannot properly gamma-carboxylate the above factors in the liver, despite the presence of vitamin K. This is the basis for parenteral (non-oral) vitamin K administration in patients with elevated RT values. ... If this therapy corrects the PT value, liver function is likely to be within normal limits, and the deficiency is most likely due to obstruction. Therefore, it is useful to re-measure the PT value after administration of vitamin K.

One of the first steps in evaluating a newborn with cholestasis is to measure PT / PTT and administer vitamin K. Untreated hypoprothrombinemia can lead to spontaneous bleeding and intracranial hemorrhage.

Micronutrients and Vitamin-Related Disorders
Copper accumulates in the liver during cholestasis as it is excreted primarily through the bile. It is possible that the interaction between copper, a prooxidant that generates free radicals, and the liver already affected by cholestasis (in the presence of depletion of antioxidants such as glutathione and vitamin E) further contributes to pre-existing liver damage.

Manganese is also excreted primarily through the biliary system and therefore can accumulate in the liver and cause hepatotoxicity. For this reason, we reduce or even discontinue the addition of manganese in solutions for complete parenteral nutrition used for patients with liver disease.

Aluminum is also excreted through biliary excretion and is hepatotoxic in high doses. Cholestasis can lead to its buildup in the liver.

Fat-soluble vitamins (A, D, E and K) are all absorbed due to adequate hepatic secretion of bile acids into the intestinal lumen. When bile acids are not excreted in the intestine, fat-soluble vitamins are malabsorbed. Moreover, the esters of vitamins A and E require hydrolysis before absorption, and, depending on bile acids, intestinal esterase catalyzes this reaction. Consequently, the absorption of vitamins A and E is further reduced in patients with cholestasis. The liver is also responsible for one of the hydroxylation steps required to metabolize vitamin D to its active form. Undoubtedly, impaired hepatic function usually lowers vitamin D levels, and rickets is common among children with cholestasis.

IMAGING AND HYSTOPATOLOGY OF THE LIVER AND BILIARY TRACT

Abdominal ultrasonography -
relatively inexpensive, easy to administer, and can usually be attempted without sedating the patient. It measures the size of the liver, confirms changes in liver structure and the presence of cystic or non-cystic parechimatous lesions. Common bile duct cysts and stones can be detected with an accuracy of 95%. Ultrasonography is also useful as a screening method for large lesions of the liver and dilated bile ducts. Finally, it also allows confirmation of the absence of a gallbladder, which may suggest the presence of biliary atresia.

Cholescintigraphy -
reveals abnormalities in hepatic seizure, as well as parenchymal concentrating and excreting abilities. Imaging with cholephilic radiolabeled N-substituted imino diacetate (IDA) labeled with technetium-99, such as diisopropyl-IDA (DISIDA) or para-isopropyl-IDA (PIPIDA), are used to screen children with liver disease. These radiolabeled atoms are concentrated within the bile, thus giving an image of the flow of bile, even in the presence of severe cholestasis. The appearance of a labeled atom within the intestinal region after 24 hours virtually excludes biliary atresia, but the opposite is not true. In fact, the absence of a tagged atom in the intestine may not represent an obstructive defect, but rather a parenchymal painful process in which the capture or concentration of the tagged atom is poor. To facilitate the flow of bile, patients often receive phenobarbital (5 mg / kg per day, divided into 2 daily doses) for 3-5 days before being scanned. Phenobarbital facilitates bile flow by inducing specific liver enzymes in infants with immature hepatic enzyme systems but no other abnormalities.

In general, radionuclide excretory scans are not essential for the assessment of neonatal cholestasis. This time-consuming process has the potential to delay diagnosis. Moreover, it has high false positive (i.e. no excretion) and false negative (i.e. overt excretion of the tagged atom) rates (at least 10%) and is not very effective when serum bilirubin levels are elevated. ... A percutaneous liver biopsy should never be delayed for a radionuclide scan.

Computed tomography (CT) and magnetic resonance imaging (MRI)
These two methods are rarely necessary as first-order methods for diagnosing liver disease in children. However, they can be useful in specific situations. A CT scan of the liver can reveal deposits of glycogen, iron, and lipids within the hepatic parenchyma and can clearly identify and characterize neoplasms in the liver. However, CT is more expensive and technically more difficult in infants than ultrasonography, and the patient is exposed to ionizing radiation. MRI has comparable sensitivity to CT in recognizing chemical differences in tissues and detecting tumors and infiltrates without injection of a contrast agent or exposure of the patient to ionizing radiation. However, MRI is more expensive and cannot be used to detect calcium deposits or in patients with implanted metal devices.

Percutaneous liver biopsy -
cardinal method for quickly arriving at a diagnosis of the underlying liver disease. Fast, safe and effective, the technique usually does not require the patient to be in the operating room or hospitalized overnight. The histological picture of the liver can be examined; glycogen, copper, iron and other components in liver tissue can be quantified. Pathologists can determine if there is any storage disorder: confirm the presence of Wilson's disease (copper storage), glycogen storage disease or neonatal iron storage disease, and many other pathological conditions. The histological picture of the tissue provides useful information about the degree of fibrosis or the presence of cirrhosis and allows the diagnosis of biliary atresia, neonatal hepatitis, congenital hepatic fibrosis, and alpha-1-antitrypsin deficiency. It has been reported that percutaneous liver biopsy can provide accurate diagnosis of biliary atresia in 94-97% of all cases, thus eliminating the risk of exposing a child with cholestasis caused by intrahepatic bile duct insufficiency to unnecessary surgical intervention.

ABBREVIATIONS
AIH - Autoimmune Hepatitis
ALT - alanine aminotransferase
AR - alkaline phosphatase
AST - aspartate aminotransferase
GGT - Gamma Glutamyl Transpeptidase
HAV - hepatitis A virus
HVB - hepatitis B virus
HCV - hepatitis C virus
HDV - hepatitis D virus
HEV - hepatitis E virus
LFT - liver function test
RT - prothrombin time
PTT - Partial Thromboplastin Time

LIVER DISEASES IN A NEWBORN

Neonatal hepatitis

This relatively specific syndrome has been characterized both clinically and histologically, but its pathophysiological basis is unknown.

A small percentage of cases may be associated with viral hepatitis acquired in utero or postnatally.

In most cases, "idiopathic" neonatal hepatitis is a very general category that includes all cases of neonatal liver dysfunction whose etiology has not been identified.

For example, homozygous alpha-1-antitrypsin deficiency, which is now recognized as a specific cause of liver disease in neonates, was previously included in the category of idiopathic neonatal hepatitis.

As bile acid metabolism is more clearly defined and specific defects are identified, it is now believed that many children previously thought to have "neonatal hepatitis" have a bile acid metabolism defect.

Hepatobiliary systems in infants and newborns are susceptible to damage from immaturity metabolic processes, insufficient transport of proteins, or altered organelle function. These characteristics lead to altered permeability or inefficient transport within the system, which contributes to the onset or chronicity of cholestasis.

The primary goal in the management of children with neonatal hepatitis is to conduct an exhaustive search for identifiable and treatable causes of this clinical condition. Jaundice may occur from birth or appear within the first 3 months of life.

The classic manifestations of cholestasis are not always present during the first few weeks of life in patients with bile duct insufficiency, alpha1-antitrypsin insufficiency, or even biliary atresia. These children often, but not always, have poor appetite, vomiting, and a sick appearance.

Cholestasis is manifested by the discharge of acholic stools and dark urine... The serum bilirubin level is elevated and more than 50% of the indicator is due to the conjugated fraction. Aminotransferase levels are almost always elevated, but to varying degrees. AP and GGT levels, if elevated, then only moderately.

Serum albumin and RT may be abnormal, and the degree of deviation correlates with the severity of the disease at the initial presentation. Ultrasonography usually shows the presence of a gallbladder and the absence of cystic malformations of the biliary tree that explain cholestasis. Hepatobiliary scintigraphy detects slow transport of the radionuclide and ultimately shows an open extrahepatic biliary tree.

Severely affected liver may have difficulty uptake of the radionuclide, which reduces the usefulness this study in seriously ill children. Liver biopsy usually provides a definitive diagnosis by demonstrating the transformation of giant cells by inflammatory infiltrates of the portal zones and the absence of proliferation of the bile ducts.

The management of these children involves supportive measures and avoiding the effects of malabsorption by ensuring adequate nutrition and intake of fat-soluble vitamins and medium chain triglycerides until recovery (which occurs in most). Liver transplantation is an alternative for those who do not benefit from conservative treatment.

Biliary atresia

Biliary atresia is the result of a destructive idiopathic inflammatory process that affects intra- and extrahepatic bile ducts. This leads to fibrosis and obliteration of the biliary tract with the development of biliary cirrhosis. It occurs worldwide, affecting approximately 1 in 12,000 live births, and is the most common indication for liver transplantation in infants and children.

The early differentiation of biliary atresia from idiopathic neonatal hepatitis allows for rapid surgical correction (Kasai portoenterostomy), which allows for improved nutrition and maximum growth.

Because cirrhosis develops rapidly, surgical correction of biliary atresia is most effective when performed before 3 months of age, highlighting the need for rapid and accurate diagnosis of the cause of the infant's liver dysfunction. As with idiopathic neonatal hepatitis, children with biliary atresia present with signs of cholestasis. Once these signs are recognized, abdominal ultrasonography can rule out the presence of a common bile duct cyst.

Cholescintigraphy usually shows good capture of the tagged atom and no excretion into the intestine even after 24 hours. Liver biopsy confirms the diagnosis - reveals proliferation of interlobular bile ducts, periportal fibrosis and bile plugs in the tubules.

Liver transplantation may become necessary if there is progressive hepatic decompensation, refractory growth retardation, impaired synthetic dysfunction, and development of coagulopathy or difficult-to-control portal hypertension with recurrent gastrointestinal bleeding or hypersplenism.

Other reasons

Other nosological units leading to liver dysfunction in the newborn and infant can be diagnosed by a combination of general studies.

Structural abnormalities of the biliary tree, such as congenital hepatic fibrosis or holedochus cysts, are usually detected by ultrasonography. Liver biopsy shows the characteristic “ductal lamina defect” in infants with congenital hepatic fibrosis.

Bacterial infections causing cholestasis can be identified by a positive culture of blood or urine. Mother's contact with a history of infection or previous infection (toxoplasmosis, syphilis, cytomegalovirus, herpes simplex virus, chickenpox and other viruses) should encourage testing for these infections. In the case of a suspected viral infection, antibodies to both serum immunoglobulin M (IgM) and IgG should be determined. Urine is often positive for cytomegalovirus.

Hereditary tyrosinemia, a defect in tyrosine metabolism, is indicated by disproportionate violations of hepatic synthetic function, mild deviations in bilirubin, transaminase levels, and rickets

The presence of succinyl acetone in urine and the detection of insufficient activity of fumarylacetoacetate hydrolase (which catalyzes the final stage of oxidative catabolism of tyrosine) confirms the diagnosis. Screening for alpha 1-antitrypsin deficiency can be done by typing the protein inhibitor ZZ (PiZZ) and is usually confirmed by the characteristic Schiff periodic acid - positive alpha 1-antitrypsin granules deposited within the hepatic parenchyma on liver biopsy.

Excess iron deposits are seen on biopsies in infants with neonatal iron storage disease. Congenital hypothyroidism, which may manifest as vague hyperbilirubinemia, is ruled out by assessing thyroid function.

LIVER DISEASES IN AN OLDER CHILD

The main causes of liver disease after infancy are toxic, infectious, metabolic, autoimmune, vascular, and infiltrative. The relative frequency of each disorder varies with the age of the patient. Viral hepatitis occurs in patients of all ages, as does liver disease caused by cardiac or collagen vascular disease.

Fat metabolism disorders are noted in older infancy and early childhood. Wilson's disease is usually diagnosed in older childhood or adolescence.

Acute hepatitis

The clinical picture of viral hepatitis varies depending on the pathogen. HAV infection manifests itself most often as a flu-like illness (malaise and signs of upper respiratory tract). Patients often have fever and jaundice can be very severe.

The pathogens are spread primarily through the fecal-oral route. In children, the disease is usually self-limited and often has no clinical manifestations. No chronic carrier state has been identified. Diagnostics acute infection based on the presence of anti-HAV IgM antibodies in serum.

Hepatitis B virus (HAV) infection can cause both acute and chronic hepatitis and possibly the development of cirrhosis and hepatocellular carcinoma. Diagnosis is based on the detection of hepatitis B surface antigen (HBsAg) or anti-HBV nuclear (anti-HBc) IgM antibody. Chronic HBV infection is associated with persistence of HBsAg and HBV DNA.

Hepatitis C virus (HCV) causes acute hepatitis, which progresses to chronic disease in more than 70% of affected people. End-stage disease (liver cirrhosis, hepatocellular carcinoma) may occur in 10% of patients. Fulminant hepatitis has rarely been reported. The diagnosis is based on the detection of anti-HCV antibodies and is confirmed by a polymerase chain reaction for HCV RNA.

Hepatitis D virus (HDV) infection usually complicates liver disease in a patient with hepatitis B, and should always be considered in patients with particularly aggressive HBV disease. HDV is widespread in the Mediterranean basin and is less common in North America, where it is associated primarily with intravenous drug use.

The hepatitis E virus (HEV) occurs as an epidemic in parts of the world with poor sanitation. Cases diagnosed in North America have been reported in patients who brought the virus from overseas. It can be a particularly devastating condition in pregnant women.

Chronic hepatitis

It is traditionally defined as inflammatory liver disease in which biochemical and histological abnormalities persist for more than 6 months. However, irreversible changes can occur in children and within the given 6 months.

The most acute hepatitis disappears in children within 3 months.

The etiology of the observed liver disease should be actively identified, since many of the diseases that cause chronic hepatitis in children are amenable to specific conservative therapy. Chronic hepatitis in children is the result of a viral infection, an autoimmune process, exposure to hepatotoxic drugs, or cardiac metabolic or systemic disorders.

Autoimmune hepatitis (AIH)

AIH is inflammation of the liver associated with the presence of circulating autoantibodies in the absence of other recognized causes of liver disease. At least two types have been described: type I AIH is more common in women and is characterized by a positive antinuclear antibody, and type II AIH involves anti-liver-kidney-microsomal antibodies.

Other autoimmune diseases can coexist with this type of hepatitis, including thyroiditis, diabetes, hemolytic anemia, and erythema nodosum. Laboratory evaluation reveals elevations in aminotransferases (often very high) and varying degrees of hyperbilirubinemia, most of which is conjugated.

Serum gammaglobulin concentrations are elevated in almost all patients. AP and GGT indicators are usually normal or only slightly increased. Liver biopsy reveals inflammatory infiltrates of the limiting plate and intralobular zones with partial necrosis, distortion of the lobular structure, and even fibrosis in severe cases.

Other liver diseases

Sclerosing cholangitis is characterized by a chronic inflammatory process of the intra- or extrahepatic biliary tree. It may be primary (no evidence of an underlying disease and unclear etiology) and is commonly associated with inflammatory bowel disease. Secondary sclerosing cholangitis results from stones, postoperative strictures, or tumors.

Children may experience jaundice, pruritus (itching), or fatigue on presentation. Elevated AR levels are very characteristic, but there is no specific marker of the disease. The biopsy shows typical concentric fibrosis around the interlobular bile ducts (onion skin appearance). Cholangiography or endoscopic retrograde cholangiopancreatography is necessary for the diagnosis.

Treatment involves the administration of fat-soluble vitamins and ursodeoxycholic acid, a natural choleretic bile acid that appears to reduce pruritis in affected individuals.

Unfortunately, liver disease progresses in many patients and cirrhosis develops. Long-term survival ultimately requires liver transplantation.

Wilson's disease - An autosomal recessive disorder caused by a defect in biliary copper excretion in which excess copper deposits lead to cirrhosis. Excess copper is deposited in the cornea, kidneys and brain, leading to extrahepatic manifestations of the disease.

Although clinical manifestations can be extremely variable, Wilson's disease should be included in differential diagnosis any child with liver disease, neurologic abnormalities, behavioral changes, or Kayser-Fleischer rings.

Serum ceruloplasmin, the carrier of copper, is usually, but not always, reduced. A definitive diagnosis requires an assessment of the 24-hour urinary copper excretion and the quantification of copper in liver biopsies.

Wilson's disease can present as fulminant liver failure, usually associated with a hemolytic crisis due to the toxic effects of copper on red blood cells.

Therapy is penicylamine, which makes it possible for copper to be excreted in the urine. Because the prognosis depends on early treatment and individual response to therapy, it is important to consider this diagnosis in every child with signs of chronic liver disease.

Ischemic hepatitis occurs as a result of congestive heart failure, shock (eg, dehydration), asphyxia, cardiac and respiratory arrest, or seizures. Usually, aminotransferases are elevated in the absence of other markers of severe liver disease. This disorder is caused by hypotension / hypoperfusion of the liver during one of the above events, the liver is affected as an "innocent bystander" of the initial process.

Ischemic hepatitis may resemble infectious hepatitis, but is easily distinguished by the rapid decline in transaminase levels during the days following the initial stroke without increasing coagulopathy or hyperbilirubinemia.

Infiltrative disorders of the liver are observed when leukemia, lymphoma and neuroblastoma , but these nosological units are usually quickly identified. In a similar way, primary liver tumors are easily identified in a child who presents with hepatomegaly or abdominal distention. Less commonly, children initially present with jaundice and retardation.

Hepatoblastoma, hepatocarcinoma, and hemangioendothelioma account for nearly two-thirds of all childhood hepatic tumors. Hepatocellular carcinoma tends to develop later in life than hepatoblastoma and is more common in children with a history of liver disease (eg, chronic hepatitis B).

Serum AFP levels are usually elevated. CT scans usually reveal

The liver is one of the most important organs human body... It performs many functions, producing bile, taking an active part in metabolic processes and cleansing the body of various aggressive substances. However, in some cases, its activities may be disrupted. Moreover, such failures can be observed even in childhood, including during the neonatal period. Let's talk on this page www.site about what are the severe liver diseases in children, the symptoms, consider them, and also answer the question of what diet is indicated for such disorders in young patients.

What are the severe liver diseases in children?

The most famous severe liver diseases in childhood are considered to be hepatitis. In certain cases, they can even occur in newborn babies. More rare pathological conditions are considered to be abscesses of this organ, as well as cirrhosis. Sometimes doctors are also faced with tumor lesions of the liver in children, which in 57% of cases turn out to be malignant.

Symptoms

Viral hepatitis in children can manifest itself in the most different symptoms, depending on its type, as well as on the development option (typical and atypical). Also, the disease can proceed in an acute form, chronic and protracted. At the initial stage of development, hepatitis sometimes manifests itself with the classic symptoms of SARS (cough, nasal congestion, weakness, lack of appetite and fever). The disease can also make itself felt with painful sensations in the epigastric region, nausea, weakness and vomiting (which resembles food poisoning). The onset of hepatitis can manifest as weakness, drowsiness, excessive fatigue, headaches, and decreased appetite.

Next stage the development of hepatitis (preicteric) is manifested by painful sensations in the joints, rashes on the skin, and over time, darkening of urine and enlarged liver. Next comes the icteric period, in which the skin and mucous membranes quickly turn into icteric shades. Initially, such a symptom is noticeable on the sclera and mucous membranes of the mouth, then on the face, trunk, and limbs. Severe jaundice may be accompanied by itching, hemorrhagic manifestations and increased intoxication. Signs of damage to the central nervous system are especially dangerous: noticeable lethargy and anxiety, problems with sleep.

Especially severe forms hepatitis symptoms of intoxication and central nervous system damage increase especially rapidly, there may be loss of consciousness, shortness of breath, rapid heartbeat, fever and cramps. At the same time, the liver is painful.

Cirrhosis of the liver in children is rare. Such a disease is manifested at first by the usual malaise, weakness, headaches, drowsiness, loss of appetite, subferral fever, dry skin, nosebleeds. Sometimes there is jaundice, flatulence, diarrhea or constipation, nausea, dull pain in the liver. Young patients may experience telangiectasias and itchy skin.

Liver abscess in children develops extremely rarely, for example, with purulent lesions of the abdominal cavity, infection of the navel, etc. Early symptoms of this condition include chills, which are accompanied by high fever, frequent pulse and high fever. The liver enlarges slightly and becomes painful, jaundice of varying intensity is observed.

Tumors and liver cancer are not very pronounced. The most basic symptom of such conditions is considered to be an increase in the abdomen. The development of the disease can become the cause of general weakness, nausea, vomiting, decreased appetite, weight loss and fever. It is also possible for fluid to accumulate in the abdominal cavity - ascites.

Treatment

The diet for liver disease in children is aimed at making the work of this organ as easy as possible. The patient's diet should include a significant amount of easily digestible protein, as well as fiber, vitamins and minerals. In this case, the patient should limit the intake of fats into the body, especially of animal origin, as well as those products that activate the secretion of digestive juice. In general, the dietary food for young patients with liver diseases is based on the Pevzner diet No. 5 and on the principle of “well-being”.

With liver ailments, it is worth eating regularly in rather small portions - five to six times a day with an interval of three to four hours. The diet should contain milk and a variety of dairy products (natural and without preservatives with a low level of fat). Meat should be consumed only boiled, steamed, baked or stewed, giving preference to beef, veal and chicken (breast). Fish can be eaten boiled and not fatty, for example, pike perch, cod, navaga, perch, ice fish. Various vegetables and fruits, as well as dishes based on them, will be beneficial. Soups should be cooked with vegetable, cereal or dairy soups. The diet can include cereals, as well as flour products. From sweets, it is allowed to eat honey, marshmallow, marmalade and jam.

With liver ailments, it is worth reducing consumption butter(no more than 30-40g), eggs (2 per week, steamed), cheese (you can only mild), sausages (you can only dietary, doctoral, dining), caviar, herring and tomato.

With early diagnosis, even severe liver disease in children can be successfully treated.

Detection of liver diseases at an early stage makes it possible to block the pathological process, thereby preventing the occurrence serious consequences... Given the multifunctionality and importance of the liver for a child, one can only guess what complications may appear against the background of its failure.

Unfortunately, in pediatrics, cases are often recorded when under the guise of physiological jaundice occurs serious disease liver.

Features of the course of liver disease in children

Clinical symptoms in older children practically do not differ from symptoms in adults. As for newborns, in the first year of life, diseases that are hereditary in nature begin to appear.

In the first two weeks after birth, such a sign of dysfunction of the hepatobiliary tract, such as yellowness of the skin, appears. It occurs due to intrauterine underdevelopment of the ducts (atresia), when there is no patency of the biliary tract, or against the background of feeding the baby with fat milk.

Jaundice can also develop in response to the introduction of complementary foods and changes in the mother's diet against the background of fructose intolerance or lactase deficiency.

The cause of jaundice may lie in a hereditary disorder of bile outflow, familial cholestasis, which is diagnosed in the first month of life. In addition to icterus (yellowing) of mucous membranes and skin, discoloration of feces is noted.

In addition, a baby is observed if a pregnant woman has suffered an acute infection, abused alcohol or took hepatotoxic drugs while carrying a fetus.

Symptoms of liver disease in children

Difficulties in diagnosing diseases in childhood are due to limited number permitted examination methods, as well as the lack of verbal contact with the patient in the first years of life. Signs of liver disease in a child include manifestations of not only damage to the hepatobiliary tract, but also dysfunction of the digestive and nervous systems.

An early symptom of liver pathology is presented pain syndrome, which is localized in the area of ​​the right hypochondrium. The intensity of the pain is increased by fatty foods and running. It can be cramping, cutting, bursting, or aching. Sometimes there are attacks of pain lasting up to a quarter of an hour.

In addition, liver diseases in children are manifested:

In addition, sleep disorder is observed, due to which the child becomes moody, whiny and sleepy during the day.

Causes of pain in the liver area

Symptoms of the pathology of the hepatobiliary system largely depend on the cause of its occurrence. In any case, pain in the area of ​​the right hypochondrium is not the norm and requires careful diagnosis. Children may have pain in the hepatic region due to:

1. physical activity;
2. abuse of fatty foods;
3. stretching of the liver capsule due to hepatomegaly (enlargement of the gland);
4. disorders of bile outflow.

Exercise stress

Pain syndrome in the area of ​​the right hypochondrium can occur after heavy physical exertion. Many of us have experienced colic or heaviness in the hepatic region after running or exercising.

In this case, the child's liver hurts due to its filling with blood. The fact is that during physical exertion, a redistribution of blood occurs, due to which the volume of the organ increases somewhat, while stretching the capsule. The severity and soreness is due to irritation of its nerve receptors.

To avoid the appearance of pain, it is recommended to do a warm-up before power loads or jogging. In addition, it is necessary to observe the time interval after meals and before sports activities. During exercise, it is forbidden to drink a lot of fluids, you need to breathe correctly and take breaks between approaches.

Improper nutrition

Each of us knows that the liver is actively involved in digestion. One of its main functions is to synthesize bile, which accumulates in the bladder, where it gets rid of excess water and becomes more concentrated. It is necessary for:

1. breakdown of fats;
2. stimulation of intestinal motility;
3. neutralizing the acidity of food that comes from the stomach, where it was exposed to hydrochloric acid and pepsin;
4. maintaining the microflora of the ducts, thereby preventing the development of infectious inflammation;
5. removing cholesterol, toxins and bilirubin from the body;
6. stimulation of the synthesis of hormones (secretin, cholecystokinin), which activate digestive enzymes.

When using fatty foods, hot spices, a large number sweets, fried foods or smoked meats, the load on the liver increases significantly. As a result, its volume increases slightly, the capsule stretches, and soreness appears in the area of ​​the right hypochondrium.

Stretching the fibrous capsule

Painful sensations can occur due to stretching of the fibrous capsule with an increase in the volume of hepatic tissue. It is necessary to highlight such liver diseases in children, which are accompanied by hepatomegaly:

The list of pathological conditions in which bile outflow is disturbed is presented:

The diagnostic process begins with interviewing the patient's complaints. The child must tell what bothers him and show where it hurts. Then the doctor conducts a physical examination, focusing on the color of the mucous membranes and skin, and also probes the area of ​​the right hypochondrium, where hepatomegaly and tenderness can be detected.

After interviewing the parents and analyzing the data obtained, the doctor determines the range of diagnostic examinations that will allow him to confirm the disease.

Instrumental methods

To visualize internal organs, in particular the hepatobiliary system, a specialist prescribes an ultrasound examination. It is considered the safest for children and can be repeated many times. During the examination, waves that pass through tissues of different densities are reflected on the screen in shades of greater or lesser intensity. Thus, the doctor can determine the size, structure of the liver, visualize ducts, calculi, additional formations or developmental anomalies.

To assess the contractility of the bladder and the state of the sphincter of Oddi, ultrasound is repeated after breakfast. It should contain foods that stimulate bile outflow.

According to the indications, duodenal intubation can be performed, which makes it possible to analyze the portion volumes and composition of bile. For a more detailed examination, cholecysto- or cholangiopancreatography is used.

Blood tests

Laboratory diagnostics includes:

Liver function tests

The biochemical blood test includes many indicators, however, not all the doctor uses to diagnose liver diseases. Decoding of the results is carried out taking into account age norms... Blood must be donated on an empty stomach. If the material is taken from a baby, the specialist must take into account the time when the baby last ate.

The analysis often examines the following indicators:

1. alanine aminotransferase. The enzyme is found in many cells of the body, mostly in the liver and kidneys. With an increase in its level in the blood, one should suspect hepatitis, leukemia, metastatic lesion of the gland, Infectious mononucleosis, metabolic disorders or liver hypoxia;
2. aspartate aminotransferase. The enzyme is found in the liver and myocardium. Normally, it is absent in the blood, so its appearance indicates tissue damage in hepatitis, tumors, mononucleosis and metabolic disorders;
3. gamma glutamyl transferase. Its maximum content is noted in the liver, kidneys, and also the pancreas. With its increase, hepatitis, intoxication, intra- and extrahepatic stagnation of bile should be excluded.

With a decrease in the level of gamma-glutamyltransferase, hypothyroidism should be suspected, which is very dangerous in childhood and can lead to a delay in mental and physical development.

1. alkaline phosphatase. The maximum amount of it is in the liver, and therefore its increase is observed in infectious hepatitis, tumors, the presence of stones in the ducts, abscesses in the gland or mononucleosis. Alkaline phosphatase is not always a reliable indicator of liver disease. The fact is that it is also synthesized in bone tissue, as a result of which its increase can be observed against the background of a rapid increase in the growth of the child;
2. total bilirubin is a product of destruction of erythrocytes, which enters the liver for excretion from the body with bile. With cholestasis, its level in the bloodstream rises. This is observed in hemolytic jaundice, hepatitis, cystic fibrosis, obstruction of the biliary ducts due to blockage of the lumen with a stone or against the background of atresia of the outflow tract.

Treatment

The doctor's tactics are based on the results of laboratory and instrumental diagnostics. The earlier treatment begins, the less severe the complications of the disease will be. One of the important points of therapy is diet.

The child is assigned a table number 5, which allows you to reduce the load on the hepatobiliary system and normalize the bile outflow. Here are the basic principles of nutrition:

If the baby is breastfed, the mother is affected by the nutritional restrictions.

Medication assistance

Conservative treatment tactics include the use of medicines, the action of which is aimed at eliminating the cause of the pathology and alleviating the condition of the little patient. The doctor may prescribe:

At an advanced stage of gallstone disease, surgical removal of the bladder may be required, which is called cholecystectomy. The intervention is performed using laparoscopic instruments. With atresia of the bile ducts, anastomoses are formed to restore bile outflow.

In severe cases of liver damage, transplantation may be considered.

Physiotherapy exercises, galvanization, psychotherapy and physiotherapy procedures, such as paraffin baths, electrophoresis and massage, have proven themselves well. They are used in combination with medications and in the postoperative period.

Prevention of liver disease consists in proper nutrition, sports activities and regular checkups by a pediatrician.