Severe liver disease in children, symptoms, diet. Treatment of the liver in children

Liver diseases in children are hereditary and acquired, can manifest or occur at any age. In the first month of life, the child may experience symptoms of hepatomegaly - a moderate enlargement of the liver in children is a condition of the body, 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 by 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.

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

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

With natural (neonatal) jaundice:

  • newborn skin acquires yellow tint not 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 disappear completely. All this time the child should be active, eat well and sleep well.

Symptoms of pathological jaundice in a newborn:

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

With these signs, you should immediately go to the hospital to measure and monitor the dynamics of the level of bilirubin, undergo an ultrasound scan of the liver to detect damage bile ducts and violations of the outflow of bile, and the delivery of liver tests ALT and AST.

If an infant has physiological jaundice, glucose preparations, vitamins, and herbal medicine are prescribed as maintenance of 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 problems with digestion.

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. AT severe cases appointed surgical intervention, blood transfusion and other procedures in a hospital setting.

Hepatitis (jaundice)

If, against the background of yellowing of the skin, a 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 loses coordination of movements, probably. General intoxication of the body can lead to death.

Viral hepatitis

Transmitted to an infant from an infected mother during childbirth, an older child can catch 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 a hospital: the virus persists on poorly sterilized instruments.

Toxic hepatitis

Occurs due to drug overdose, poisoning household chemicals, food poisoning. In adolescent children, it can develop against the background of taking alcoholic beverages.

autoimmune hepatitis

A pathology in which liver cells destroy their own the immune system person. In a child's body that has not been fully formed, the progressive process of damage to one of the main hematopoietic organs occurs faster than in an adult. Liver tissue dies and is replaced by scar tissue, leading to cirrhosis.

fatty hepatitis

Occurs in children suffering from obesity and diseases of the pancreas. Liver tissues are reborn due to the accumulation of fat in them, the organ begins to function defectively.

Every third child preschool age suffering from giardiasis. Children under 3 years of age have a hard time with the disease, since at this age, when infected, a high temperature rises, appear severe nausea, there is vomiting.

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

Giardiasis can be suspected in a child by frequent fatty, fetid stools.

Obstruction of the bile ducts

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

Tumor diseases

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

Liver disorders

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

  • Icteric hue of the skin and yellowness of the sclera;
  • constantly holding on subfebrile temperature from 37.1°C to 38°C without signs of a cold and pain - this indicates sluggish latent inflammatory processes, which is typical for hepatic pathologies;
  • Dark colored urine
  • Colorless feces;
  • Nausea
  • Lack of appetite.

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

In children 5-7 years old, the biliary system is actively developing. In this regard, moderate hepatomegaly, a small but palpable enlargement of the liver, may be observed. The child may experience mild ailments, the skin may turn yellow. This is due to age physiology, and does not speak of illness. There is no need for any treatment, but a diet indicated 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; in necessary cases – choleretic agents. Laparoscopy is done - a bloodless operation, if necessary - abdominal.

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

This house stands on the right bank, and the largest digestive gland lives in it - the Liver.
She works day and night: she accumulates nutrients and vitamins, produces bile, which promotes the breakdown and absorption of fats, takes part in the metabolic process, in the synthesis of blood tanks, and regulates blood clotting factors. Lives, year after year becomes older, weighs more. The liver is very homely: it loves well-cooked food and does not accept drugs and alcohol, but it also does not like chemical agents very much. When the Liver gets angry and sick, then it is bad for the whole house, for all its inhabitants.

  1. The child has a slight yellowness of the skin, and on palpation, a slightly enlarged edge of the liver is felt, there is slight soreness in the right side. You are upset and would not even want to think that the marked signs indicate a disease, although, alas, this is not excluded. Liver diseases occupy one of the first places among diseases of the gastrointestinal tract in children aged 3-7 years. The main reasons are irregular meals, changes in the quality of food products, the appearance of allergens in food and water, psycho-emotional overstrain.
  2. You came home from work and, by moving the bundles and pots in the refrigerator, you realized that the soup was not warmed up, and the boiled condensed milk and a piece of sausage were eaten. Your child is in the 3rd grade, which means that the student has been eating dry food for the third year. You have often noticed his frequent belching. This is a sign that the liver is out of order. Obviously, you need to keep a diary of the meal report or provide for forced control measures.
  3. Mom was alerted that a 3-year-old baby slept only on her left side or on her back. Mom remembered that even earlier the girl often cried when she was laid on the right side. AT medical institution functional changes in the liver were diagnosed. The reason was the early transfer of the girl to artificial and mixed feeding.
  4. Returning from the kindergarten, the son was happy to eat pasties (from the kiosk). It turned out that in kindergarten the boy never ate anything. Why? Because he is not used to eating porridge, mashed potatoes, soup, pasta. At home, the “road” way of eating prevailed: what could be eaten right there was bought. In fact, all parents can be advised: while the child is small, at least cook properly for him (the first course, fruits, salads). Start keeping a food diary, find out what the baby ate today in kindergarten, at school, and what at home.
  5. Keep notes where you note important little things and nuances. For example: on what date did quarantine for the virus start in kindergarten; what additional tasks the child was loaded with after kindergarten, school; how he reacted to the remark whether he had a seasonal malaise; how the intestines work. All this is very important for the timely recognition of liver diseases. The child may complain of nausea, belching, dryness and bitterness in the mouth. At the same time, during pain in the right hypochondrium, a yellow stool is noted, the head hurts, the mood is depressed, and fatigue quickly comes. These are all signs of liver disease.

Wheatgrass - A WEED OR A MEDICINE?

It heals and strengthens the liver, so it’s inconvenient to somehow call it a weed. 1 teaspoon of couch grass, wild rose and nettle is poured into a glass of water, boiled, cooled, filtered and taken half a glass half an hour before meals and at night. The decoction is useful for both children and adults, it is not only curative, but also a good prophylactic. If your child has (or has had) liver and gallbladder disorders, be sure to use this recipe.

Drink without limits

Another infusion is also useful for regulating the activity of the liver: 300 g of grass and 50 g of immortelle flowers are poured with two glasses of boiling water and left to infuse overnight. In the morning, filter and give to drink instead of water, without restrictions.

Children's fee

But the collection, which in traditional medicine has long been considered for children: 200 g of St. John's wort, knotweed, calendula flowers, 15 g of buckthorn bark and 5 g of pharmacy chamomile. Don't let "grams" confuse you, because the proportion of herbs taken for the infusion is important. Take 2 tablespoons of this collection, pour 0.5 liters of cold water and put it overnight. In the morning, after boiling for 5-7 minutes, insist for half an hour in a warm place, then strain. The resulting infusion should be drunk in several doses.

Symptoms of liver disease are similar to those of acute gastrointestinal diseases and an attack of appendicitis. Here, the named decoctions will not help - urgent medical attention is needed. Therefore, it is better to refuse self-diagnosis and treatment.

BE AFRAID OF OILY DONUTS

At the first symptoms of the disease (dull It's a dull pain in the right side, heartburn, lack of appetite) a warm heating pad on the right side for 1.5-2 hours before bedtime for three days, as well as acupressure in the gallbladder area (under the last rib vertically down from the right nipple) can help. Plus cleansing enemas at night 2-3 times a week. It is desirable that the child sits quietly with his right leg tucked under him twice or thrice a day. This posture promotes the flow of bile.

WE WILL STRIKE FROM TWO FRONTS

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 operation 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 kind of severe liver diseases are in children, consider the symptoms, and also answer the question of what diet is indicated for such disorders in young patients.

What are severe liver diseases in children?

The most famous severe liver disease in childhood is 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 also encounter 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 with a variety of symptoms, depending on its type, as well as on the developmental variant (typical and atypical). Also, the disease can occur in acute form, chronic and protracted. At the initial stage of development, hepatitis is sometimes manifested by the classic symptoms of SARS (cough, nasal congestion, weakness, lack of appetite and fever). Another disease can make itself felt painful sensations in the epigastric region, nausea, weakness and vomiting (which resembles food poisoning). The onset of hepatitis can be manifested by weakness, drowsiness, excessive fatigue, headaches, and decreased appetite.

The next stage in the development of hepatitis (preicteric) is manifested by painful sensations in the joints, rashes on the skin, and over time, darkening of the urine and an increase in the liver. Then comes the icteric period, in which the skin and mucous membranes quickly turn into icteric shades. At first, 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 an increase in toxicity. Especially dangerous are the signs of CNS damage: noticeable lethargy and anxiety, problems with sleep.

When especially severe forms hepatitis, symptoms of intoxication and CNS damage increase especially rapidly, loss of consciousness, shortness of breath, rapid heartbeat, fever and convulsions. The liver is painful.

Cirrhosis of the liver in children is rare. Such a disease is manifested initially by the usual malaise, weakness, headaches, drowsiness, loss of appetite, subfertile temperature, dry skin, nosebleeds. Sometimes there is jaundice, flatulence, diarrhea or constipation, nausea, dull pain in the region of the liver. In young patients, telangiectasia and pruritus may occur.

Liver abscess in children develops extremely rarely, for example, with purulent lesions abdominal cavity, infection of the navel, etc. Early symptoms of this condition include chills, which is accompanied by high fever, rapid pulse and high fever. The liver slightly enlarges 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 cause general weakness, nausea, vomiting, loss of appetite, weight loss and fever. It is also possible the accumulation of fluid in the abdominal cavity - ascites.

Treatment

The diet for liver disease in children is aimed at facilitating the work of this organ as much as possible. The patient's diet should include a significant amount of easily digestible protein, as well as fiber, vitamin and mineral elements. 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, dietary nutrition for young patients with liver disease is based on the Pevzner diet No. 5 and on the principle of “well-being”.

With liver ailments, it is worth eating regularly in fairly 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 low fat content). Meat should be consumed only boiled, steamed, baked or stewed, preferring 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 benefit. Soups should be prepared vegetable, cereal or dairy. The diet can include cereals, as well as flour products. From sweets, it is allowed to eat honey, marshmallow, marmalade and jam.

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

With early diagnosis, even severe illness liver in children can be successfully cropped.

Often, parents pay attention to the yellow complexion of the child, constant complaints of nausea, lack of appetite, decreased activity. It is possible that there are serious liver problems in a child that require mandatory consideration. This organ plays one of the main roles in the proper functioning of the body, therefore, if a child has problems with the liver, you should definitely consult a doctor.

Practice shows how important early diagnosis of diseases in children is. A liver problem in a child can appear from the moment of his birth, therefore, its identification is necessary at an early stage in order to prevent an unfavorable course of the disease and its negative consequences. The causes of liver problems in a child are due to: cholestatic disorders (biliary duct insufficiency, thickening of bile), viral hepatitis, other infectious diseases (herpes virus, toxoplasma, enterovirus), hereditary metabolic diseases (diabetes mellitus, impaired carbohydrate metabolism), toxic effects on organism (hypervitaminosis A, certain types of drugs, general parenteral nutrition).

Symptoms associated with liver problems in a child can be both pronounced and worn. weak character, which is the reason for the untimely appeal to a specialist. However, the main clinical manifestations various diseases liver are characterized by: constant crying of the newborn due to pain, refusal of the baby to eat, nausea of ​​the child, bouts of vomiting, severe salivation, bad smell from the mouth, bloating, constipation, diarrhea, rapid fatigue of the child, irritability of the baby.

All these symptoms should alert parents and serve as a signal to see a doctor.

Often, the symptoms listed above may be absent, as a result of which parents are unaware of the adverse course of certain diseases. However, in most cases, you can visually notice the increased size of the liver, contributing to the asymmetry of the abdomen.

To identify problems with the liver and make an accurate diagnosis, it is necessary to pass a series of tests. These are: feces, blood and urine. All these tests can determine whether there are violations of the functions of the digestive organs, in particular, the liver.

Treatment of liver diseases in a child can be either medical or surgical, and the choice of one of them depends on the cause of the problem, as well as its neglect. Often, drug therapy is combined with diet therapy, in which all foods harmful to the liver are excluded from the child's diet. As for medicines, the main attention is paid to homeopathic remedies that gently restore the liver, cleansing it and preventing the development of problems.

At the same time, the choice of homeopathic remedies should be dealt with by the doctor himself, since some of them have a strong choleretic action and can aggravate the condition of the baby. In addition, the parents of the child must understand that an independent attempt to cure their baby can lead to serious consequences, since without the results of examinations and tests at hand, it is impossible to determine true reason ailments. Thus, the attentiveness of parents, the responsibility of the doctor, the right treatment, as well as the observance of a strict diet - all these measures will save the baby from problems with the liver.

Often the greatest effect of the treatment is achieved with the obligatory observance of a strict diet, designed specifically for those who have serious liver problems. Therefore, diet is an obligatory and integral part of treatment.

Liver problems in a child can occur for various reasons, both congenital and acquired. Regardless of what led to the development of liver disease and disruption of its work, it is required mandatory treatment following a strict diet.

This information is intended for healthcare and pharmaceutical professionals. Patients should not use this information as medical advice or recommendations.

Liver disease in children

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

Early recognition is especially important in neonates and infants, as a delay in diagnosis can be Negative influence for the forecast.

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

Moreover, as liver dysfunction progresses, early recognition allows for more successful nutritional management of the patient and potentially slowing the decline in liver function. The result may be improved growth and reduced 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 the patient childhood with severe liver disease).

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

Hence, various violations often have virtually identical initial manifestations.

For example, newborns with liver disease 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 documented a number of factors contributing to late referral of children with liver disease (Table 1).

Table 1
Reasons for delayed referral for children with liver disease

  • Lack of follow-up for neonatal jaundice (including failure 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 presence of pigmented stools

ETIOLOGY

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

Table 2.
Most common causes liver disease in children of all ages

NEWBORN AND INFANTS

cholestatic disorders

  • - Biliary atresia
  • - choledochal cyst
  • - Insufficiency of intrahepatic bile ducts (eg Allagile syndrome)
  • - Syndromes of progressive familial intrahepatic cholestasis (Byler's disease and syndrome)
  • - Benign recurrent intrahepatic cholestasis (Caroli disease and syndrome)
  • - Thickening of bile (S/P hemolytic disease)
  • - Cholelithiasis

    Idiopathic neonatal hepatitis and diseases mimicking it

  • - 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

  • - Peroxysmal function disorders (Zellweger syndrome)
  • - Metabolic disorders bile acids
  • - Urea cycle disorders (arginase deficiency)
  • - Amino acid metabolism disorders (tyrosinemia)
  • - Lipid metabolism disorders (Niemann-Pick type C/Gaucher/Wolman)
  • - Disorders of carbohydrate metabolism (galactosemia, fructosemia, glycogen storage disease type IV)

    Toxic/pharmacological injury (eg, acetaminophen (paracetamol), total parenteral nutrition, hypervitaminosis A)

    Tumors (intra- and extrahepatic)

    Biliary atresia and idiopathic neonatal hepatitis observed only at birth or shortly thereafter. Conversely, alcohol or acetaminophen intoxication and Wilms' disease are common in older children, especially adolescents.

    Moreover, while "neonatal hepatitis" may 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 are 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 a neonate who presents with classic features such as persistent jaundice, hepatomegaly, coagulopathy, or underweight.
    In other cases, this is an accidental finding of abnormalities in the study of serum.
    Jaundice, confusion, and coma have been reported in older children and adolescents with acute hepatitis or after exposure to the toxin. Itching observed in older children may be regarded as irritability in infants.

    HISTORY AND SIGNS OF LIVER DISEASE

    Newborn

    Although the infant may have already had jaundice at birth (physiological hyperbilirubinemia) or is breastfed, it is important not to attribute jaundice in a child older than 14 days to one of these causes.

    Jaundice in any child older than 2 weeks of age should raise suspicion of liver disease and prompt appropriate evaluation.

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

    For example, the onset of liver disease associated with changes in diet may raise the suspicion of an inborn disorder of carbohydrate metabolism, such as an inability to metabolize galactose or fructose.

    A positive family history for a suspected genetic disorder should focus the initial evaluation 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 among boys, especially premature and low birth weight infants.

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

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

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

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

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

    Moreover, the disintegration of the stool into pieces usually shows that the pigment is only superficial, while its interior is at best the color of clay.

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

    older child

    In older children with a history of anorexia. fever, vomiting, abdominal pain, 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 increased performance aminotransferases in the absence of any established contact with hepatotoxic substances. Hepatitis A is often anicteric in children younger than 5 years of age and often goes unrecognized.

    Signs of liver disease in patients who have had tattoos, who have used intravenous drugs, or in whom any disease 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, consider co-infection or superinfection with hepatitis (D) delta.

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

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

    Confusion and coma raise suspicion of liver failure or metabolic disease leading to hyperammonemia, hypoglycemia, and a combination of both.
    Adolescent girls who develop jaundice and have a history of acne, intermittent arthritis, and fatigue may have 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.

    Upper right quadrant colic and a history of nausea (especially after eating a fatty meal) suggests gallbladder disease, which is more common in older children.

    Signs and symptoms of obesity of cardiac, endocrine, or intestinal disease should be taken into account, since abnormalities in serum aminotransferase may reflect secondary liver damage in systemic disease (the liver as an "innocent bystander").
    An increase in the concentration of aminotransferases (especially AST) can also be a manifestation of muscle disease.

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

    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 reduce the surface tension of solutions, thus creating visible foam.

    PHYSICAL MANIFESTATIONS

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

    Table 3
    Diseases that cause jaundice/elevated liver enzymes

    BABY
    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-Pick disease, tyrosinemia
  • - Acquired: cholestasis and liver disease caused by total parenteral nutrition, hypothyroidism, panhypopituitarism
  • - Idiopathic disorders
  • - Neonatal hepatitis, progressive familial intrahepatic cholestasis (eg Byler disease),
  • Ivemark syndrome, cerebrohepatorenal (Zellweger) syndrome

    • Malformations of bile streams

    • - Atresia / insufficiency of intrahepatic bile ducts, non-syndromic and syndromic (Allagile syndrome)
    • - Cystic malformations: choledochal cysts, cystic dilatation of the intrahepatic bile ducts (Caroli disease), congenital hepatic fibrosis, polycystic liver and kidney disease.

      OLDER AND GROWER CHILDREN

    Acute viral hepatitis (HAV)

    Hereditary diseases:

    • wilson's disease,
    • cystic fibrosis,
    • hepatic porphyria,
    • Dubin-Johnson Syndrome,
    • Rotor syndrome

    Malignant diseases:

    • leukemia,
    • lymphoma,
    • liver tumors

    Chemical substances:

    • hepatotoxic drugs,
    • toxins (hydrocarbons intesticides, alcohol, organophosphates, hypervitaminosis A, fungi, acetaminophen).
    • schistosomiasis,
    • leptospirosis,
    • visceral larva migrans

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

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

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

      Therefore, measuring the width of the liver is a useful adjunct to palpation at initial presentation and follow-up.
      The width of the liver is the distance between the edge of the liver and the upper limit of 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 margin 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 the presence of cirrhosis or the Riedel lobe (normal anatomical elongation of the right lobe, which can be mistaken for hepatomegaly).

      Table 4
      Diseases that cause hepatomegaly

    INFANTS AND CHILDREN
    storage diseases

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

    Tumors

    • - primary: hepatoblastoma, hematoma, hemangioendothelioma
    • - metastasizing: neuroblastoma, Wilms' tumor, tumors of the gonads.

      Table 5
      Diseases that cause liver failure

      NEWBORN AND INFANTS

    Infections:

    • herpesviruses,
    • echo,
    • adenoviruses,
    • sepsis.
      Metabolic disorders: hereditary fructose intolerance,
    • mitochondrial diseases,
    • tyrosinemia,
    • galactosemia,
    • neonatal iron storage disease.
      Ischemia/shock:
    • myocarditis,
    • severe hypotension.
      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 infiltration of the liver during pregnancy.

      Table 6
      Various physical manifestations associated with liver disease

      BABY
      Microcephaly:

    • congenital cytomegalovirus,
    • rubella,
    • toxoplasmosis
      characteristic type faces:
    • arteriohepatic dysplasia (Allagile syndrome)
      Cataract:
    • galactosemia
      Retinal pigmentation: Allagille syndrome
      Abnormal manifestations on auscultation of the lungs: cystic fibrosis.
      Neuromuscular disorders (tremor, lethargy): lipid storage disease, Wilson's disease, oxidative phosphorylation disorders

      CHILDREN
      Pruritus:

    • 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 may also reveal the presence of an enlarged spleen, which is usually normal size on the early dates 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 dilatation of the Glisson capsule due to edema, which is responsible for the felt pain localized to the liver region.

    Severe hepatosplenomegaly is indicative of storage disease or malignancy, although particularly prominent hepatomegaly is itself associated with severe hepatic fibrosis

    In this condition, the kidneys should 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 due to anatomical vascular malformations or increased blood flow to the liver.

    Ascites suggests increased portal venous pressure and worsening hepatic function.

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

    Dysmorphic features may be characteristic of certain chromosomal disorders. Patients with Alagille syndrome usually have a characteristic facial pattern (beak nose, high forehead, butterfly-shaped vertebrae, and murmurs on cardiovascular auscultation due to peripheral pulmonary stenosis and posterior embryotoxin in ophthalmological examination.

    The presence of intermittent vomiting in a newborn, especially unremitting, may indicate an inborn metabolic disorder that is usually also associated with poor nutritional status and irritability. The occurrence of symptoms (such as vomiting) after the introduction of a new product containing galactose or fructose could raise the 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 EVALUATION

    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 considerable 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 found in bile or are eliminated through bile are usually increased in cholestatic conditions. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), and conjugated bilirubin (all requiring a pure biliary tree for elimination) are usually elevated.

    Conversely, necrosis of hepatocytes following viral or toxic liver stroke (eg, acetaminophen overdose or viral hepatitis) usually primarily causes an increase in hepatocyte-intrinsic enzymes such as aminotransferases (ALT and AST). In hepatocellular disease, serum levels of GGT and AP 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 poisonous accumulation of bile within the hepatocytes and biliary tree. In hepatocellular disease, reduced biliary blood flow (sludge) that results from necrosis of hepatocytes also causes a slight increase in serum markers of obstruction (AP, GGT).

    The two main types of liver disease can be differentiated early in the disease process, but most often, the underlying type of liver disease is diagnosed by interpretation of a combination of clinical and laboratory criteria, including liver biopsy. This is especially true for neonates and infants, where there is 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 preterm infants in whom the presence of jaundice after 14 days of age requires evaluation. Table 7 shows the goals for the stepwise assessment of infants with jaundice.

    Table 7
    Objectives for stepwise assessment of infants with jaundice
    Recognize cholestasis (unconjugated or physiological hyperbilirubinemia)
    Assess the severity of liver damage
    Separate specific nosological units (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 suggested for infants presenting at 2 months of age with cholestasis to quickly 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
    - Assessment of stool color
    - Index of hepatic synthetic function (prothrombin and albumin time)

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

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

    Liver function studies

    Because the liver has a large functional reserve, abnormal laboratory values ​​are often the only manifestation of overt hepatic disease and may occur long before overt clinical manifestations. In the usual scenario, a doctor who suspects liver disease will usually order "specific liver function tests" (LFTs) to evaluate liver function. Consistently monitoring these parameters can provide information on prognosis, response to therapy, and degree of dysfunction.

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

    Biochemical abnormalities associated with liver disease are not limited to LFT abnormalities. For example, nonketotic hypoglycemia suggests a beta-oxidation defect fatty acids and production of ketones. Severe ketosis, a rare finding in infants, may indicate organic acidemia, glycogen storage disease, or neurogenesis deficiency. An increase in anion shift in metabolic acidosis also suggests organic acidemia. Hypo- and hyperthyroidism may be associated with jaundice. Determination of sweat chlorides may be required to rule out cystic fibrosis. Iron and ferritin studies are useful in diagnosing neonatal iron storage disease. Determination of bile acid levels in urine and serum usually helps in ruling out the possibility of congenital disorders of bile acid metabolism. Urinary succinylacetone levels may indicate the presence of tyrosinemia. Urinalysis 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 laboratory investigations conducted, bilirubin fractionation is the most important.
    A healthy mature liver removes unconjugated bilirubin from the blood and mediates the conjugation of unconjugated bilirubin with two molecules of glucuronic acid. Conjugation of bilirubin converts an essentially fat-soluble substance (unconjugated bilirubin) into a water-soluble substance (conjugated bilirubin) that can be excreted into the bile, aquatic environment. It is the fat-soluble nature of unconjugated bilirubin that allows it to cross the blood-brain barrier and potentially cause kernicterus.

    Physiological neonatal jaundice (in which levels of unconjugated bilirubin increase) results from the immaturity of the glucuronyl transferase system responsible for bilirubin conjugation. jaundice associated with breastfeeding(a slight temporary delay in conjugation ability), usually the result of components contained 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 kernicterus in the newborn.
    In the presence of conjugated (direct, bound) bilirubin, the evaluation should be aggressive. Serum conjugated bilirubin greater than 17 mcmol/L (1 mg/dL) or greater than 15% of overall indicator bilirubin should be considered abnormal and evaluated immediately! Unconjugated bilirubin levels reflect excess production of bilirubin (eg, as a result of hemolysis) or a reduced ability of the liver to bind bilirubin. The conjugated fraction is associated with serious liver disease and is indicative of 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 the urine. Most of the urobilinogen is excreted in the stool as coprobilinogen; 20% undergoes enterohepatic recirculation. Only a small fraction enters the urine, but this is increased in the presence of hepatocellular injury due to reduced hepatic uptake and recycling. Undoubtedly, urinary urobilinogen is almost absent in the presence of an obstructive process, since less bilirubin penetrates 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 an initial cholestatic stroke, since its disappearance depends on the breakdown of albumin. -bilirubin complex.

    Aminotransferase activity
    Alanine aminotransferase (ALT) (formerly known as serum glutamic pyruvate transferase - SGPT) and AST (formerly known as serum glutamic oxaloacetic transaminase -SGOT) levels are the most sensitive assays for hepatocyte necrolysis. A significant increase in these enzymes, which are released from damaged hepatocytes, indicates hepatocellular damage. Mildly disturbed levels may also be associated with cholestatic processes, as bile backflow or stasis 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 pyruvic acid (ALT) and oxaloacetic acid (AST).

    ALT is more specific for the presence of liver disease because it is found only at low concentrations in other tissues (eg, muscle). Conversely, AST is found in high concentrations in many tissues, including cardiac and skeletal muscle, kidneys, pancreas, and red blood cells. The coenzyme of both enzymes is vitamin B6, so it is persistently abnormal low rates AST and ALT suggest an underlying vitamin B6 deficiency.

    In general, aminotransferase levels 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 abnormal values ​​may do well, especially in the case of acetaminophen toxicity. However, they are useful in monitoring the patient's clinical progress, for example, progressively lower AST/ALT values ​​in a young patient who has HAV infection and is otherwise doing well is a comforting sign that the liver disease is disappearing. Conversely, declining AST/ALT values ​​in the presence of a shrunken liver, 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 to the tubular membrane of liver cells, therefore an elevated serum AP 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 commonly found in children during periods of accelerated growth, such as pubertal growth spurts. Particularly high levels should lead to suspected possible pathology bones (eg, rickets), especially if the increase in AP is not associated with an increase in GGT. If the levels of the latter enzyme are also elevated, bone disease is unlikely. This simple observation reduces the need to fractionate AP values ​​into individual isoenzymes to determine the exact source of their increase. For example, zinc-coenzyme-AP - persistently low levels of AP may mean low serum levels of zinc.

    Serum and urine bile acids
    The production and transport process that occurs in the liver (bile acid synthesis, conjugation and secretion) maintains cholesterol levels, facilitates bile flow, and provides surface active detergent molecules that promote intestinal absorption of lipids. The proper functioning of this system contributes to the balance between the absorption of bile acids from the intestine and their uptake by hepatocytes. In the absence of ileal changes (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 still 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 levels of bile acids 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. The interpretation of elevated serum bile acid levels in neonates and infants is complicated by the presence of a relative "physiologic cholestasis" that 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 metabolite precursors makes it possible to identify specific congenital disorders of bile acid metabolism. With the help of recent technological advances, such as fast atom bombardmnet - mass spectrometry (mass spectrometry of fast atomic bombardment), it is possible to quickly analyze urine samples from individuals with suspected specific disorders of bile acids and identify specific congenital disorders of bile acid metabolism, such as insufficiency 3 -beta-hydroxysteroid dehydrogenase/isomerase and delta-4-3-oxosteriod-5-beta reductase deficiency, which manifest as severe liver disease.

    Gamma-glutamyl transferase (GGT)
    GGT - found 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.

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

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

    Ammonia
    Ammonia production occurs as a result of the action of colon bacteria on proteins in the diet, and the liver plays a major role in its elimination. 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 fasted state and transported quickly to the laboratory on ice, dramatically elevated 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 (malnutrition is a risk group). Because it is a fat-soluble vitamin, vitamin K deficiency is common among people with obstructive liver disease, in whom the bile acids still do not reach the intestines. Therefore, PT, the time required for prothrombin (factor II) to turn into thrombin, is usually increased in the presence of biliary obstruction. The RT can also be elevated in the presence of true hepatocellular disease, a poorly functioning liver cannot properly gamma-carboxylate the aforementioned factors in the liver despite the presence of vitamin K. This is the basis for parenteral administration(non-oral) vitamin K in patients with elevated TA values. If this therapy corrects the PT value, liver function is likely to be within normal limits and the failure 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 because it is excreted primarily through the bile. It is possible that the interaction between copper, a pro-oxidant that generates free radicals, and a liver already affected by cholestasis (in the presence of depletion of antioxidants such as glutathione and vitamin E) further contributes to the already 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 are reducing or even discontinuing manganese supplementation in total parenteral nutrition solutions used for patients with liver disease.

    Aluminum is also excreted via biliary excretion and is hepatotoxic at high doses. Cholestasis can lead to its accumulation in the liver.

    The fat-soluble vitamins (A, D, E, and K) are all absorbed through adequate hepatic secretion of bile acids into the intestinal lumen. When bile acids are not excreted into the intestine, malabsorption of fat-soluble vitamins occurs. Moreover, vitamin A and E esters require hydrolysis before absorption, and bile acid-dependent 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 into its active form. Undoubtedly, impaired hepatic function usually reduces vitamin D levels, and rickets is common among children with cholestasis.

    IMAGING AND HISTOPATOLOGY OF THE LIVER AND BILIAL TRACT

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

    Cholescintigraphy -
    reveals abnormalities in hepatic uptake, as well as parenchymal concentrating and excreting abilities. Imaging with cholephilic N-substituted iminodiacetate (IDA) radiolabeled, technetium-99 radiolabeled atoms, such as diisopropyl-IDA (DISIDA) or para-isopropyl-IDA (PIPIDA) are used in the examination of children with liver disease. These radiolabeled atoms are concentrated within the bile, thus giving an image of bile flow, even in the presence of severe cholestasis. The appearance of a labeled atom within the intestinal region after 24 hours virtually rules out biliary atresia, but the reverse is not true. In fact, the absence of a tagged atom in the gut may not represent an obstructive defect, but rather a parenchymal disease process in which tagged atom uptake or concentration 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 having a scan. 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 assessing 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., clear tagged atom excretion) rates (at least 10%) and is not very effective when serum bilirubin levels are elevated. . Percutaneous liver biopsy should never be delayed in favor of a radionuclide scan.

    Computed tomography (CT) and magnetic resonance imaging (MRI)
    These two methods are rarely necessary as first-order methods in the diagnosis of liver disease in children. However, they may be useful in specific situations. CT scanning 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 injecting a contrast agent or exposing 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. The technique is fast, safe and effective and usually does not require the patient to stay in the operating room or stay overnight in the hospital. 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: to confirm the presence of Wilson's disease (copper storage), glycogen storage disease, or neonatal iron storage disease, as well as 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 an accurate diagnosis of biliary atresia in 94-97% of all cases, thus eliminating the risk of exposing a child with intrahepatic bile duct insufficiency cholestasis to unnecessary surgical intervention.

    ABBREVIATIONS
    AIH - autoimmune hepatitis
    AR - alkaline phosphatase

    HAV - hepatitis A virus
    HVB - hepatitis B virus
    HCV - hepatitis C virus
    HDV - hepatitis D virus
    HEV - hepatitis E virus
    RT - prothrombin 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 for which an etiology has not been identified.

    For example, homozygous alpha-1 antitrypsin deficiency, which is now recognized as a specific cause of neonatal liver disease, was formerly 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 defect in bile acid metabolism.

    The hepatobiliary systems of infants and newborns are susceptible to damage due to metabolic immaturity, insufficient protein transport, 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 detectable and treatable causes of this clinical condition. Jaundice may occur from birth or appear during 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 deficiency, or even biliary atresia. These children often, but not always, have poor appetite, vomiting, and a sick appearance.

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

    Serum albumin and RT may be abnormal, and the degree of abnormality correlates with disease severity at presentation. Ultrasonography usually shows the presence of the gallbladder and the absence of cystic malformations of the biliary tree, explaining cholestasis. Hepatobiliary scintigraphy reveals delayed transport of the radionuclide and eventually shows an open extrahepatic biliary tree.

    A severely affected liver may have difficulty absorbing the radionuclide, reducing the usefulness of this study in seriously ill children. Liver biopsy usually provides a definitive diagnosis by demonstrating giant cell transformation with portal inflammatory infiltrates and no bile duct proliferation.

    Management of these children involves supportive measures and avoidance of the consequences of malabsorption by providing 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 the 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 frequent indication to liver transplantation in infants and children.

    Early differentiation of biliary atresia from idiopathic neonatal hepatitis allows rapid surgical correction (Kasai portoenterostomy) that allows improved nutrition and maximum growth.

    Because cirrhosis develops rapidly, surgical repair of biliary atresia is most effective if performed before 3 months of age, emphasizing the need for rapid and accurate diagnosis causes of liver dysfunction observed in the infant. 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 choledochal cyst.

    Cholescintigraphy usually shows good capture of the labeled atom and no excretion into the intestine even after 24 hours. A 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 the development of coagulopathy or intractable portal hypertension with recurrent gastrointestinal bleeding or hypersplenism.

    Other reasons

    Other nosological units that lead 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 choledochal cysts, are usually detected by ultrasonography. Liver biopsy shows the characteristic "ductal plate defect" in infants with congenital hepatic fibrosis.

    Bacterial infections that cause cholestasis can be identified by a positive culture of blood or urine. Maternal exposure to or previous infection (toxoplasmosis, syphilis, cytomegalovirus, herpes simplex virus, varicella, and other viruses) should prompt screening 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 impairment of hepatic synthetic function, mild abnormalities in bilirubin, transaminase levels, and rickets.

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

    Excess iron deposits are seen on biopsy in infants with neonatal iron storage disease. Congenital hypothyroidism, which may present with vague hyperbilirubinemia, is ruled out by evaluation of thyroid function.

    LIVER DISEASES IN AN OLDER CHILD

    The main causes of liver disease seen 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 presents most often as a flu-like illness (malaise and signs of an upper respiratory tract infection). Patients often have a fever and may have very severe jaundice.

    The pathogens spread primarily through the fecal-oral route. In children, the disease is usually self-limiting 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 cirrhosis and hepatocellular carcinoma. Diagnosis is based on detection of hepatitis B surface antigen (HBsAg) or anti-HBV core (anti-HBc) IgM antibody. Chronic HBV infection is associated with the persistence of HBsAg and HBV DNA.

    Hepatitis C virus (HCV) causes acute hepatitis that 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 described. The diagnosis is based on the detection of anti-HCV antibodies and is confirmed by the 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 prevalent in the Mediterranean basin and less common in North America, where it is primarily associated with intravenous drug use.

    Hepatitis E virus (HEV) occurs as an epidemic in parts of the world with poor sanitation. The cases diagnosed in North America were in patients who brought the virus from abroad. It can be especially devastating in pregnant women.

    chronic hepatitis

    It is traditionally defined as an 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 among women and is characterized by a positive antinuclear antibody, and type II AIH involves anti-liver-kidney-microsomal antibodies.

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

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

    Other liver diseases

    Sclerosing cholangitis is characterized by chronic inflammation of the intra- or extrahepatic biliary tree. It may be primary (without evidence of 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 present with jaundice, pruritis (itching), or fatigue upon presentation. Elevated AR levels are very characteristic, but there is no specific disease marker. Biopsy shows typical concentric fibrosis around the interlobular bile ducts (an "onion skin" appearance). Cholangiography or endoscopic retrograde cholangiopancreatography is required to make 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. Liver transplantation is ultimately required for long-term survival.

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

    Serum ceruloplasmin, the carrier of copper, is usually, but not always, reduced. Definitive diagnosis requires assessment of 24-hour urinary copper excretion and copper quantification in liver tissue obtained by biopsy.

    Wilson's disease may present as fulminant hepatic failure, usually in association with a hemolytic crisis due to copper toxicity to red blood cells.

    The therapy is penicillamine, which allows the excretion of copper into the urine. Since the forecast depends on early treatment and individual response to therapy, it is important to consider this diagnosis in every child with evidence of chronic liver disease.

    Ischemic hepatitis occurs as a result of congestive heart failure, shock (eg, dehydration), asphyxia, cardiac and respiratory arrest, or convulsions. 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 a rapid decrease in transaminase levels during the days following the initial stroke without increasing coagulopathy or hyperbilirubinemia.

    Infiltrative disorders of the liver are observed with 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 lag in the masses.

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

    Serum levels of alpha-fetoprotein are usually elevated. CT scanning usually reveals low-density lesions and shows whether the mass is single or multiple. Surgical excision of a single tumor or radiation/chemotherapy is the treatment of choice.

    CONCLUSION

    The identification of severe liver disease in a pediatric patient at initial presentation is of critical importance. Early identification of children with biliary atresia is critical for optimal conservative or surgical intervention.
    Achievement is the availability of numerous treatment options for liver disease other than transplantation (Table 9).

    Table 9
    Options for children with liver disease other than transplant

    • Replacement of a deficient abnormal end product, such as oral administration of primary (basic?) bile acids (in patients with impaired bile acid biosynthesis)
    • Reduced accumulated substance (eg, antioxidant cocktails and binding in neonatal iron storage disease)
    • Use of metabolic inhibitors (eg, NTBC for tyrosinemia)
    • Enzyme induction (eg, phenobarbital for Crigler-Najjar type II syndrome)
    • Dietary substrate restriction (eg, galactose in galactosemia)
    • Molecular manipulation (eg, inhibition of alpha 1-antitrypsin polymerization)
    • Receptor-Based Targeted Enzyme Replacement Therapy
    • Gene therapy
    • Hepatocyte transplantation (eg, fulminant liver failure)

    These new management strategies are more expensive, but they reduce the use of valuable donor livers, making these organs available to patients who still have no other treatment options.

    In the future, under certain metabolic disorders crucial therapies such as targeted enzyme replacement or gene therapy may be available. Given these exciting prospects, correct and prompt assessment of liver disease in children is of paramount importance to enable them to grow and be as healthy as possible until they reach an age at which definitive therapy can be available.

    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

    Source : Ian D. D" Agata, Williams F. Balistreri. Evaluation of Liver Diseases in the Pediatric Patient. Pediatric in Review, Vol. 20, No 11, pp 376-389

    Translation from English– N.N. Cherkashina

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