A child has a weak liver. Liver cleansing in children – is it treatment or prevention? Older child

Diseases in children associated with abnormal liver function can occur for various reasons. In any case they represent serious threat for the health and development of the child.

The liver is one of the main organs, the work of which affects all the others. It is responsible for hematopoiesis, nutrition of tissues with substances necessary for the construction of cells, and for the removal of toxic substances from the body.

Liver diseases in a child

Liver diseases cannot always be detected immediately, since the symptoms of most childhood diseases are similar in the initial stages. A clear symptom is jaundice. Timely detection of this type of deviation in a child is especially important, as it will give a chance to get rid of the ailment with the least complications.

Deviations in the functioning of this organ in children can occur for the following reasons:

The child's body quickly reacts to any discomfort. Slight hypothermia, unusual food, stress can cause fever, indigestion, changes in mood and other symptoms. Such symptoms cannot be ignored. They can cause serious illness.

The following deviations should attract the attention of parents:

Symptoms of the disease - yellowing of the skin and whites of the eyes

Symptoms can be smoothed out, especially in the presence of colds. This can even confuse a doctor. As a rule, he prescribes urine and blood tests. Judging by the color of urine, one can even visually suspect a liver disorder in a child. General analysis blood will show the content of the dye bilirubin produced by the liver. Hemoglobin level in healthy child is normal or slightly underestimated. With hepatitis, the hemoglobin content is increased. Blood clotting also depends on the condition of the liver. Decreased clotting may be a sign of disease. The number of red blood cells and platelets also changes. After studying the test results, the doctor decides whether to refer the child for a more complex examination. A urine test will show the concentration of bilirubin, the presence of toxic compounds, and an increased content of leukocytes, indicating an inflammatory process.

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Liver diseases can occur in children at any age.

Liver disease in newborns and infants

Due to natural underdevelopment biliary tract, which is possible during the prenatal period, the liver of newborns may not immediately adapt to normal conditions. So-called physiological jaundice appears. The cause of yellowing of the body and eyes in newborns may be breastfeeding if the mother full fat milk. Usually, until two weeks of age, this jaundice does not pose a danger and goes away on its own. If jaundice does not go away after 2 weeks, then the cause may be a disease. The child must be examined and, if the disease is confirmed, treated, paying attention to the slightest changes in condition. The complication can be very dangerous, as it usually occurs suddenly (it is also called “kernicterus”) and leads to the death of the child.

Jaundice in a baby can also occur if the nursing mother’s diet changes. The body can react to fruits and milk. This condition occurs with lactose intolerance or fructose intolerance. In order to exclude an abnormality in the baby, it is enough for the mother to adhere to a diet. Tests will tell you which product causes this reaction in the child’s body.

Severe form of jaundice in newborns - “kernicterus”

Sometimes the cause of jaundice in a child can be hereditary disorder circulation of bile in the body (familial cholestasis). Most often this disease occurs at the age of 1 month. A sign of insufficient bile formation is white stool of heterogeneous composition with brown spots.

A common cause of infant jaundice is the presence of infectious diseases in the mother during pregnancy and childbirth. These may be infections in the urinary organs, gynecological diseases, herpes, syphilis, rubella, tuberculosis and others.

Serious diseases in infants include biliary atresia - obstruction of the biliary tract. This disease has practically no cure; a liver transplant is required. A difficult operation can have life-threatening complications (cirrhosis and others).

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Deviations can also occur if a woman takes medications, alcohol, or smokes during pregnancy or breastfeeding. The child may get toxic hepatitis.

At the age of 5-7 years, children may experience a moderate enlargement of the liver (hepatomegaly), which is most often caused by physiological reasons and occurs due to the gradual development of the biliary system in the child’s body. It may not manifest itself in any way. In some cases, jaundice and mild malaise may appear. In such cases, the child does not require treatment, he only needs dietary nutrition - low-fat, unsalted food, moderate consumption of sweets. The diet should include fruits, vegetables, cottage cheese and dairy dishes. This diet supports the immune system and promotes tissue restoration.

A common disease in children adolescence is a toxic damage to the liver tissue that occurs due to alcohol consumption, drug addiction and other bad habits.

Infection with viral hepatitis A or B may occur through sharing dishes or hygiene items with a sick relative. Infection with viral hepatitis C can be the result of accidental contact with the blood of virus carriers on medical instruments in the dentist's office, and can also occur during surgical operations or intravenous drug infusion. Manifestations of acute hepatitis in children are jaundice, itchy skin, hepatomegaly, fatigue, nervous disorders, including loss of consciousness and coma. If a child is suddenly losing weight, has stomach pain on the right side, has nausea and vomiting, then he must be seen by a doctor as quickly as possible.

If you suspect a disease, urgent examination by laboratory methods

A particularly severe form is

liver failure

In children, it can be congenital and becomes fully apparent by the age of 2-3 years. The liver tissue cells atrophy and the child dies. In older age, symptoms of liver failure are manifested by an enlarged abdomen due to the accumulation of fluid in the abdominal cavity, swelling, decreased blood clotting, and signs of poisoning.

If a disease is suspected, an urgent examination by laboratory methods is necessary. In this case, the following is carried out: general and biochemical blood tests, immunological tests to detect antibodies to viruses. With their help, you can determine how affected the liver tissue is and predict the development of the disease. Ultrasound, x-rays and other methods are used to confirm diseases. After the examination, the doctor knows exactly the nature of the disease, the stage of its development, possible complications. Severe forms of damage to the liver tissue are cirrhosis and cancer. The cause of such ailments can be a complication of chronic viral hepatitis.

Exist following methods treatment of childhood liver diseases:

Conservative - with the help of medications and diet;
Surgical - bloodless operations on the liver tissue and biliary tract (laparoscopy), as well as in the most severe cases, operations with opening of the abdominal cavity (for example, liver transplantation).

All operations on children are performed under full anesthesia.

With conservative treatment, a strict diet and freedom from physical activity and sports are prescribed. Depending on the nature of the disease, medications are prescribed: antibiotics (for infectious and inflammatory processes), hepatoprotectors (for hepatitis, cirrhosis and other serious diseases), choleretic drugs, vitamins.

Timely diagnosis and treatment, even in severe cases, can restore the child’s health and sometimes save a life.

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The liver is an important organ and the largest gland in the human body. The organ is located under the lower ribs on the right side of the abdominal area. In young children infancy the liver has a mass of about 4.5% of the total weight and occupies up to half the volume of the abdominal cavity. An enlarged liver in a baby can cause serious concern in a young mother. However, it should be borne in mind that the enlargement of the liver in infants is caused physiologically, extending beyond the edge of the lower rib by 2 - 4 cm and only at 6 - 7 years old it takes on normal dimensions - it extends under the costal arch.

The pathological process leading to diffuse changes in the tissue structure of the liver and an increase in its size is called hepatomegaly. The manifestation of signs of pathology may indicate various diseases. A specialist can easily detect liver enlargement by palpation or by lightly tapping the abdominal cavity. To confirm the diagnosis, an ultrasound procedure is prescribed. In a child in infancy, doctors note moderate hepatomegaly, which is also called age-related. However, exceeding certain limits and sizes corresponding to the baby’s age may indicate pathological hepatomegaly.

The development of an abnormal process in newborns is based on several group factors. The causes of an enlarged liver in an infant can be:

inflammatory processes based on: congenital hepatitis, intrauterine infection with rubella, herpes, toxic drug poisoning, abscess and biliary tract obstruction;
metabolic disorders in diseases of glycogenosis, mucopolysaccharidosis, Gaucher disease;
disturbances of bile and blood outflow in diseases of cirrhosis, venous stenosis and thrombosis, heart failure, Wilson's disease;
congenital liver changes (infiltration) in leukemia and hemolytic disease;
primary lesions in fibrosis;
excessive formation of Kupffer cells in septic infections, granulomatous hepatitis, excess of vitamins of group “A”.

Symptoms of pathology in an infant may not be expressed and depend on the progression of the disease. With the rapid formation of the disease, the enlarged liver becomes visually noticeable. The main symptoms of the phenomenon are:

decreased appetite. The baby does not eat well, frequent belching, nausea and vomiting occur;
frequent crying. The baby experiences discomfort and pain, the abdomen becomes enlarged and the navel swells. His stools become colorless;
constant lethargy and lethargy;
changes in skin color. The skin acquires a yellow tint.

In the maternity hospital, doctors often diagnose yellow skin and whites of the eyes in a newborn as physiological jaundice associated with metabolic disorders or Rh conflict with the mother. You should start to worry when jaundice does not go away before two weeks of age or only begins to appear after two weeks of age.

All symptoms cannot be ignored; parental passivity can lead to death.

Therapeutic measures for hepatomelagia are carried out only in combination. Since the pathology manifests itself as a symptom of the underlying disease, all drug therapy should be aimed at stopping it. For congenital hepatitis, medications are prescribed to destroy the pathogen. Various poisonings require cleansing a small organism of toxic substances. In case of heart failure, in addition to drug treatment, heart surgery may be required. Surgery may also be required to correct biliary atresia, a rare developmental anomaly.

When eliminating the root cause of liver enlargement, it is important to normalize its functions. To rehabilitate the baby’s condition, the doctor may prescribe:

medications with antibacterial and antiviral effects;
hepaprotective agents;
medicines with enzymes.

A course of treatment and drug therapy is prescribed for each little patient individually.

For all types of liver diseases, a change in nutritional intake and adherence to a diet are required that helps reduce the functional load on the weakened organ. A baby in infancy receives all the necessary nutrients from his mother’s milk and all dietary recommendations must be followed by her. The mother's diet should consist of balanced plant foods with a limited content of fatty and carbohydrate products. It is especially important to follow a diet if your baby has a metabolic disorder. Mom should limit consumption:

lard and fatty meat;
fatty varieties of fish, cheese and cottage cheese;
smoked meats and hot seasonings;
mushrooms and nuts;
fresh baked goods and chocolate;
strong tea and sweet carbonated drinks.

The success of treating a child’s enlarged liver largely depends on the underlying cause of the pathology. With physiological (age-related) enlargement of the organ, the symptoms of hepatomelagia disappear without a trace. In cases of congenital anomaly or acquired viral infection everything will depend on the effectiveness of the therapy.

Enlarged liver in a child

An enlarged liver is not an independent disease, but acts only as a symptom warning of problems in the body. The causes of an enlarged liver in a child are very numerous.

1. Inflammatory processes and diseases. accompanied by them. These include: rubella, herpes, toxoplasmosis, liver intoxication, congenital infections, toxocariasis, biliary tract obstruction, schistosomiasis, hepatitis A, B, C, liver abscess.

2. Disturbances in the outflow of bile and blood. They can be caused by heart failure, exposure to vinyl chloride, liver cirrhosis, myeloid metaplasia, portal or splenic vein thrombosis, and bile duct atresia.

3. Metabolic disorders. Disturbances can be caused by Gaucher disease, glycogenosis, Wilson disease, Niemann-Pick disease, porphyria, and amyloidosis.

4. Infiltrative lesion. It occurs due to metastases, hepatoma, hemolytic disease of the newborn, lymphoma and leukemia.

5. Increase in Kupffer cells of the liver. The increase occurs due to sepsis, hypervitaminosis A and granulomatous hepatitis.

6. Primary liver damage. It occurs due to hereditary hemorrhagic telangiectasia, multicystic disease, primary biliary cirrhosis, and congenital liver fibrosis.

Also, the size of a child's liver may temporarily increase due to poor nutrition or vaccination.

A doctor can assess the size of the liver during palpation or percussion. In addition, an ultrasound of the liver is often performed. Using ultrasound, the size of the liver is determined as accurately as possible.

In children whose age has not exceeded 7 years, the liver may well be enlarged without any reason. With age, its size becomes normal. Parents should be alert to the following symptoms observed in a child:

Changes in the lower edge of the liver;
-nausea;
-skin pigmentation;
- pain, as well as heaviness under the right rib;
-pain on palpation;
-fast fatiguability;
-vomit;
- yellowing of the skin and mucous membranes;
- spider veins on the body.

If at least some of the listed symptoms are observed, the child should be shown to a doctor.

A slightly enlarged liver in a baby may be due to jaundice of the newborn. Jaundice occurs due to an increase in bilirubin in the blood of a newborn baby. An enlarged liver in a newborn due to jaundice may be due to massive death of red blood cells or insufficient functioning of the child’s liver. Newborn jaundice usually goes away completely within 10-14 days. This condition does not require special treatment.

Most often, children of those mothers who suffered from toxicosis or diabetes during pregnancy suffer from neonatal jaundice. In addition, the causes may be asphyxia of the baby, drug intoxication, thyroid diseases, birth injuries, and hypoxia.

The reasons that cause liver enlargement in a child are quite numerous. These include:

Primary lesion (fibrosis, multiple cysts, biliary cirrhosis, hemorrhagic telangiectasia).

Inflammatory process (provocateurs - congenital infections (rubella, toxoplasmosis, herpes, cytomegalovirus), hepatitis A, B, C, toxic and drug-induced hepatitis, amebic or microbial liver abscesses, obstruction (blocking) of the bile ducts).

Obstruction of blood and bile flow (the root cause is cirrhosis, atresia (absence) of the bile ducts, portal vein thrombosis, cardiovascular failure, Wilson-Konovalov disease).

Metabolic pathology (Gaucher disease, Niemann-Pick disease, glycogenosis, mucopolysaccharidosis, amyloidosis, etc.).

Infiltration, i.e. the appearance of atypical components in cells (in hemolytic disease of newborns, leukemia, lymphoma, hemochromatosis, extramedullary type hematopoiesis).

Kupffer stellate cell hyperplasia (the main cause is sepsis, excess vitamin A, granulomatous hepatitis).

A situation where the liver of a baby is enlarged can also occur with pulmonary emphysema. Expansion of their boundaries leads to a kind of “pushing out” of the organ. This is clearly visible on a plain radiograph. However, no changes occur in the organ itself, therefore such hepatomegaly is called false. There is also the concept of moderate hepatomegaly. With infectious liver diseases, you have to cope with an increased load, which leads to an increase that disappears as the process subsides. This reaction of the body is not life-threatening, but requires observation and mandatory adequate treatment of the underlying pathology.

At the same time, it is accompanied by a number of signs:

Yellowness of the skin and mucous membranes;

Increased lethargy, tearfulness, refusal to feed;

Enlargement and bulging of the abdomen;

The appearance of a vascular “mesh” on the abdomen;

Discoloration of stool.

All these symptoms are alarming and require immediate consultation with a doctor. Issues related to hepatomegaly are dealt with by a pediatrician, an infectious disease specialist, a gastroenterologist and a hepatologist. To understand why a child’s liver is enlarged, a medical examination, anamnesis (that is, information that can directly or indirectly indicate the source of the disease) and various instrumental and laboratory research methods will be required. These include determination of markers of viral hepatitis, biochemical blood parameters, radiography, electrocardiography and echocardiography. The most reliable non-invasive diagnostic method is ultrasound examination of the liver. Ultrasound helps to accurately determine its size and changes in structure. In controversial cases, a biopsy is indicated if necessary. For hereditary diseases, medical genetic consultation is needed. The range of research can be expanded depending on the factors being sought.

Treatment - both medicinal and surgical - for hepatomegaly depends on the underlying disease that led to its appearance.

First of all, it is necessary to eliminate the cause, that is, the concomitant disease. Diet is important. You need to understand that an infant receives nutrients from a nursing mother, so the variety of food is limited primarily to her. Spicy, salty, canned foods and carbonated drinks, alcohol are excluded. You should eat steamed meat, lean fish, vegetables and fruits. Surgical intervention is required to correct congenital malformations (biliary atresia).

You have seen newborn babies on TV more than once. They are all so pink and smooth, and when they unwrapped your baby, he turned out to be completely different. Perhaps your baby is crimson and flaky, or perhaps his skin and eyes are yellow. Parents, upon hearing their baby’s diagnosis of “jaundice,” naturally become immediately frightened. They begin to get nervous and worry about the possible consequences for the child. A medical workers are often too busy or not competent enough to explain in detail to parents about their baby’s illness. In this article I will try to talk about jaundice in as much detail and clarity as possible. Can jaundice in newborns be physiological - in other words, normal? And what if the newborn has icteric (yellow-colored) skin and sclera of the eyes? First, drink 30 drops of valerian and calm down. Have you calmed down? Exactly? Well then, let's figure it out.

JAUNDICE IN NEWBORNS can be physiological or pathological. Physiological jaundice disappears without a trace within a short period of time. Pathological neonatal jaundice is caused by medical conditions and often requires close medical monitoring. Conditions in which newborn babies experience icteric staining of the skin, whites of the eyes and visible mucous membranes currently number more than 50. But, I repeat, this does not mean that your child will necessarily have this condition. And yet, now almost all types of jaundice in babies are successfully treated.

And yet the most common jaundice in children who have just been born is physiological. It occurs in approximately 60-70% of babies and appears 3-4 days after birth. Low birth weight and premature babies suffer more often, although not always. This condition is not a disease and goes away over time. It is associated with the immaturity of some systems of the child’s body responsible for the metabolism of a special substance - bilirubin.
To release oxygen from the mother's blood, the baby in her womb requires a high level of red blood cells (erythrocytes). Bilirubin is formed by the destruction of erythrocytes - red blood cells that contain hemoglobin and provide organs and tissues with oxygen. Before birth, until the baby breathes on its own, oxygen in its body is carried by red blood cells with special (fetal) hemoglobin. Immediately after birth, after his first breath, the baby stops needing oxygen from his mother; now he will receive it from the air. The child’s body no longer needs fetal hemoglobin, and it begins to lower the level of red blood cells. What to do with the extra red blood cells? Red blood cells are destroyed (one of the by-products of the destruction of red blood cells is bilirubin, which is yellow or orange) and are excreted from the body with meconium (newborn feces), which is black in color and has an oily consistency, and some is excreted in the urine.

The liver of a newborn baby is still very weak; it is not able to quickly process all this bilirubin. This bilirubin is called indirect, or free. It is insoluble, so it cannot be excreted in urine. The liver is responsible for converting it into a soluble form and excreting it with bile. Even healthy children immediately after birth often lack a special protein that ensures the transfer of bilirubin to the liver cells, where, after a series of biochemical reactions, it combines with substances that make it soluble. This is necessary so that bilirubin does not have a toxic effect and is safely excreted from the body. Several enzyme systems ensure this transformation at once. In many newborns, these systems complete their maturation and begin to function fully only a few days after birth.

As a result, it is carried by the blood throughout the body, accumulates in the skin and gives it a characteristic yellow tint. This is why jaundice is especially common among premature babies with weakened bodies.
Bilirubin levels are measured in micromoles per liter of blood and average around 100 µmol/L for newborns on the third day. The critical level for premature babies is 170 µmol/l; for full-term babies this level is usually higher. After one, maximum two, weeks, the level returns to normal and the jaundice disappears. In most cases, no treatment is required.

The functioning of the bilirubin secretion system gradually improves. Usually, after 1-2 weeks, the icteric staining of the skin disappears without causing any harm to the baby. It is now clear why neonatal jaundice in premature babies is more common, more pronounced and lasts longer than in full-term babies. And the severity of the increase in the level of bilirubin in the blood of premature infants depends not on body weight at birth, but on the degree of maturity of the fetus and the mother’s problems during pregnancy. More often, children of multiple pregnancies, newborns who have had birth injuries, and babies born to mothers with diabetes mellitus turn yellow.

With physiological jaundice general state Children, as a rule, are not affected. Only if it is very pronounced, babies become drowsy, suck lazily, and sometimes vomit. The severity of jaundice is judged not by external manifestations; the intensity of skin color does not always correspond to the level of bilirubin, but by the level direct bilirubin in blood. It reaches its maximum on the 3rd day of the child’s life. The child’s body “fights” excess bilirubin by binding it to the blood protein albumin, thereby preventing its toxic effect. But this doesn't always happen.

With a very strong increase in bilirubin levels, albumin cannot “block” it completely, and it penetrates the nervous system. This can have a toxic effect, primarily on vital nerve centers, brain. This condition is called “kernicterus” or “bilirubin encephalopathy.” Symptoms: severe drowsiness, convulsions, decreased sucking reflex. Late manifestations include deafness, paralysis, and mental retardation.

So, I’ll briefly summarize the above (otherwise I wrote a lot and it’s not entirely clear).

Appears 24-36 hours after birth (and not born yellow from the very beginning, mind you);
- increases during the first 3-4 days of life, that is, while you are in the maternity hospital. And not when you are already at home;
- disappears in the second or third week of life, anything that lasts longer is a reason to think about the physiology of this condition and about donating at least blood to check the bilirubin level;
- the skin has an orange tint, and not lemon yellow or olive (these are pathological types), although everyone’s color perception is different. It’s better to have a doctor evaluate this; when they are admitted to a medical university, they are tested for color vision.
- the child’s general condition is satisfactory, he is not lethargic, does not sleep constantly, sucks well,
- the size of the liver and spleen are not enlarged, you definitely can’t measure this yourself, but trust it to the doctor, I think he can handle it.
- the usual color of feces and urine, newborns have mustard-colored stools (see details in a separate article), and the urine is almost transparent. There should be no dark or discolored stool or urine.
- bilirubin concentration in umbilical cord blood (moment of birth) – less than 51 µmol,

- hourly increase in bilirubin in the first day of life is less than 5.1 µmol/l/hour,
- the maximum concentration of total bilirubin on days 3-4 in peripheral or venous blood is no more than 256 µmol/l in full-term infants, no more than 171 µmol/l in premature infants
- total blood bilirubin increases due to the indirect fraction
- the relative share of the direct fraction is less than 10%
- normal values hemoglobin, red blood cells and reticulocytes in clinical blood tests

They will look at all this in the maternity hospital, and I think they will tell you if something is wrong.

What to do, you ask? I answer. Previously, in case of increased levels of free bilirubin, intravenous infusion of glucose solutions, ascorbic acid, phenobarbital, choleretic agents to speed up its elimination. Now more and more specialists and clinics around the world are refusing to use drugs to treat physiological jaundice in newborns. Moreover, the use of some means has been found to be ineffective.

Today, the most effective and proven method of reducing the toxicity of bilirubin in physiological jaundice is phototherapy (light therapy). The baby’s skin is illuminated with a special installation (on average 96 hours per course). When exposed to light, bilirubin is converted into non-toxic derivatives, the main of which is called lumirubin. It has a different route of elimination, and after 12 hours it leaves the body in feces and urine.

A side effect of phototherapy may include peeling of the skin and frequent loose stools, and some children may experience drowsiness.

After stopping treatment, all phenomena disappear without a trace. And after discharge from the maternity hospital, it is worth exposing the baby to indirect sunlight as often as possible during the day.

The best prevention and treatment of physiological jaundice is early and frequent feedings. Because children with elevated bilirubin levels may increased drowsiness, they must be woken up for feeding. Colostrum, or “early milk” during the first few days, acts as a laxative and helps the meconium (original feces) pass more quickly. Bilirubin, which is converted in the liver, is also excreted along with it. If the meconium does not pass quickly, bilirubin from the intestines can reenter the bloodstream, thereby increasing the level of jaundice.

Even with very rare jaundice caused by mother's milk, it is not recommended to give up breastfeeding. This type of jaundice in newborns can be distinguished by its later appearance (after the 1st week of the child’s life). This condition is associated with the content of substances in mother’s milk that reduce the activity of enzymes that ensure the “conversion” of indirect bilirubin into soluble direct bilirubin.

Well, this is all clear, but what if this is not physiological jaundice, you ask? How to distinguish? Let's read.
Pathological jaundice most often appears during the first days after birth. Often, the liver and spleen become enlarged, feces may become discolored, and the urine becomes dark in color; sometimes bruises and pinpoint hemorrhages spontaneously appear on the newborn’s skin. A blood test shows signs of increased breakdown of red blood cells (hemolysis) and anemia.

I repeat, please remember any deviations from “ normal course» physiological jaundice (earlier (up to 24 hours) appearance or later (after 3-4 days) increase, long-term persistence (more than 3 weeks), wave-like course), the presence of pallor of the skin or a greenish tint, deterioration in the general condition of the child against the background progressive increase in jaundice, dark urine or discolored stool, an increase in the concentration of total bilirubin in the blood more than 256 µmol/l in full-term and more than 171 µmol/l in preterm), a relative increase in the direct fraction of bilirubin should be considered as signs of pathology. And this means you need to run to the doctor. For pathological jaundice, treatment is carried out by specialists. It depends entirely on the cause of this condition.

Let us dwell on the main types of pathological jaundice in more detail.

If mother and newborn are incompatible by blood type and/or Rh factor, massive destruction (hemolysis) of red blood cells occurs. Severe jaundice often occurs if the mother has blood type I, and the child has II or (less often III). It is believed that with each subsequent pregnancy the risk of such complications increases. It is for this reason that it is especially dangerous for women with a negative Rh factor to have an abortion.

Here are the main criteria by which this type of jaundice is identified:

Jaundice appears in the first 24 hours after birth (usually in the first 12 hours);
- increases during the first 3-5 days;
- begins to fade from the end of the first - beginning of the second week of life;
- the skin in case of AB0 conflict is usually bright yellow, in case of Rh conflict it may have a lemon tint (jaundice on a pale tone due to anemia in the baby);
- the general condition of the child depends on the severity of hemolysis and the degree of hyperbilirubinemia (from satisfactory to severe);
- in the first hours and days of life, as a rule, there is an increase in the size of the liver and spleen;
- usually - normal coloring of stool and urine; against the background of phototherapy, there may be a green coloration of the stool and short-term darkening of the urine;
- the concentration of bilirubin in the umbilical cord blood (moment of birth) - in mild forms of immunological conflict due to Rh factor and in all cases of ABO incompatibility is not higher than 51 µmol/l, in severe forms of immunological conflict due to Rh factor and rare factors - significantly higher than 51 µmol/ l.
- the concentration of hemoglobin in cord blood in mild cases is at the lower limit of normal, in severe cases it is significantly reduced.
- hourly increase in bilirubin in the first day of life is more than 5.1 µmol/l/hour, in severe cases – more than 8.5 µmol/l/hour.
- the maximum concentration of total bilirubin on days 3-4 in peripheral or venous blood is more than 256 µmol/l in full-term infants, more than 171 µmol/l in premature infants.
- total blood bilirubin increases mainly due to the indirect fraction.
- the relative share of the direct fraction is less than 20%.
- decrease in hemoglobin level, number of red blood cells and increase in the number of reticulocytes in clinical blood tests during 1 week of life.

The destruction of red blood cells can also be caused by various genetically determined disorders, such as microspherocytosis (Minkowski-Choffard anemia), disturbances in the structure of hemoglobin (for example, in sickle cell anemia), changes in the shape and structure of the red blood cell itself, etc. In the treatment of conditions accompanied by destruction of red blood cells, often used exchange transfusions blood to “wash out” bilirubin and antibodies that cause hemolysis.

They are characterized by:

Appear no earlier than 24 hours after birth,
- continue to increase after 4 days of life,
- do not fade away until the end of 3 weeks of life,
- the skin has an orange tint,
- the general condition of the child is usually satisfactory,
- no increase in the size of the liver and spleen,
- normal color of stool and urine,
- bilirubin concentration in cord blood is less than 51 µmol,
- hemoglobin concentration in cord blood is normal,
- hourly increase in bilirubin in the first day of life is less than 6.8 µmol/l/hour,
- the maximum concentration of total bilirubin on days 3-4 in peripheral or venous blood is more than 256 µmol/l in full-term infants, more than 171 µmol/l in premature infants,
- total blood bilirubin increases due to the indirect fraction,
- the relative share of the direct fraction is less than 10%,
- normal values of hemoglobin, red blood cells and reticulocytes in clinical blood tests.

A large group consists of jaundice, which occurs as a result of liver damage by viruses, bacteria, and protozoa. It is clear that in such cases it is impossible to do without treatment of the infectious process. Unfortunately, there are currently not effective treatments for all congenital infections. This once again emphasizes the need for careful preparation for pregnancy, especially in the presence of infectious diseases, to reduce the risk of transmitting infection to the baby.

Such jaundice is characterized by:

Early appearance of jaundice and wavy character,
- enlargement of the liver and spleen,
- early appearance of hemorrhagic syndrome (that is, bleeding),
- inconsistent nature of acholia (that is, loss of color) of stool,
- dark yellow urine,
- biochemical cholestasis syndrome (stagnation of bile, characterized by itching),
- marked increase in ALT, AST (special enzymes in the blood that characterize liver function),
- violation of the synthetic function of the liver (decreased concentrations of albumin, fibrinogen),
- visualization of the gallbladder by ultrasound.

So-called mechanical jaundice occurs due to a violation of the outflow of bile due to a bile duct cyst, annular pancreas, or atresia (underdevelopment) of the bile ducts. In this case, surgical intervention is necessary. With pyloric stenosis and intestinal obstruction, the reason for the increase in the level of bilirubin in the blood is its reabsorption from the intestine. Surgeons can also help in such situations.

They are characterized by:

Jaundice discoloration of the skin with a greenish tint (olive color),
- enlargement and thickening of the liver, less often – the spleen,
- dark urine, discolored stools,
- high levels of direct bilirubin, GGT, cholesterol and other markers of cholestasis,
- delayed, moderate increase in ALT, AST,
- Absence of disturbances in the synthetic function of the liver (normal serum levels of albumin, fibrinogen, PTI more than 80%).

a hereditary disease, very similar to physiological jaundice of newborns, is quite common. The reason for the failure in bilirubin metabolism in this case is a violation of its binding due to hereditary inferiority of liver enzyme systems. This condition usually requires treatment and is monitored by gastroenterologists.

Hormonal imbalances also cause jaundice in newborns. This happens, for example, with hypothyroidism - a decrease in functional activity thyroid gland. This form of jaundice is combined with other signs of insufficient production of thyroid hormones: large abdominal size, dry skin, low body temperature, a special, hoarse cry, constipation, swelling of the face, eyelids, delayed ossification processes, etc. Jaundice occurs with hypothyroidism at 2-3 The th day of life lasts up to 3-12 weeks, and sometimes up to 4-5 months. Treatment is carried out under the supervision of an endocrinologist using drugs - thyroid hormones.

The most serious condition requiring immediate assistance are bilirubin encephalopathy and kernicterus.

A progressive increase in the concentration of unconjugated bilirubin in the blood in some cases is accompanied by its penetration through the blood-brain barrier and accumulation in the neurons of the brain. In this case, the subcortical nuclei of the brain acquire a characteristic yellow color, due to the accumulation of bilirubin in them - “kernicterus”.

1st phase. Dominance of signs of bilirubin intoxication: suppression of unconditioned reflex activity - apathy, lethargy, drowsiness, poor sucking, maybe a monotonous cry, regurgitation, vomiting, “wandering eyes.”

Phase 2. The appearance of classic signs of kernicterus: spasticity, rigidity occipital muscles, forced position of the body with opisthotonus (bends in an arc), “stiff” limbs, clenched hands. Periodic excitement and a sharp cerebral cry, bulging of the large fontanel, twitching of the facial muscles, large-scale tremor of the hands, disappearance of the visible reaction to sound, sucking reflex, nystagmus, apnea, bradycardia, lethargy, convulsions. This phase takes from several days to several weeks. Damage to the central nervous system is irreversible.

Phase 3. The phase of false well-being and complete or partial disappearance of spasticity (2-3 months of life).

4th phase. The period of formation of the clinical picture of neurological complications (usually 3-5 months of life): cerebral palsy, paralysis, paresis, deafness, delay mental development etc.

Lead tactics.

Children need early (from the first hour of life) and regular breastfeeding.
If there are clinical signs of a severe form of hemolytic disease at the time of birth of a child in a woman with Rh negative blood(pronounced pallor of the skin, icteric staining of the skin of the abdomen and umbilical cord, swelling of the soft tissues, an increase in the size of the liver and spleen), an emergency operation of the transfusion transfusion (replacement blood transfusion) is indicated without waiting for laboratory data (In this case, the technique of partial exchange transfusion of blood is used, in which replacement of 45-90 ml/kg of child’s blood with a similar volume of donor red blood cells of group 0 (1) Rh-negative).

Without being a specialist, it is impossible to understand all the intricacies of diagnosing such a large group of diseases as jaundice in newborns (jaundice). It is important to understand that long-term persistence of icteric skin discoloration in a small child requires mandatory examination. It must certainly consist of a general blood test, determination of the level of total bilirubin and its fractions in the blood serum, liver function indicators, a hemolysis test (Coombs test), ultrasound examination of the abdominal organs, if necessary, and consultation with a surgeon or other specialist to clarify the diagnosis and timely treatment.

And in conclusion, I remind you again.

If the jaundice is small and appears on the third day, then the child is usually not touched for a month. Then, if it doesn’t go away, they begin to figure out what’s wrong.

And it could be:

1. the most common option. There is still a lot of estrogens in the child’s blood; they inhibit enzyme activity, so bilirubin binds slowly. It goes away on its own. Some are faster, some are slower.

2. The bile ducts do not allow enough bile to pass through. Maybe just narrow - then as the child grows, the problem disappears. Maybe the bile is too viscous. We need choleretic drugs.

3. a sufficient amount of bile is not produced. Not enough enzymes. Take choleretic and pancreatin. Gradually everything passes.

4. antigen constantly enters the child’s blood (sometimes with mother’s milk). Very rarely. Then - just a mixture. But this is very rare.

5. there is a possibility that the child’s immature liver did not react well to the hepatitis vaccine.

6. there is a possibility of congenital hepatitis.

I repeat, specialists should understand all this.

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

Liver diseases 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 delay in diagnosis can have a negative impact on prognosis.

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

Moreover, as liver dysfunction progresses, early recognition allows for more successful nutritional support for the patient and potentially slows the decline in liver function. The result may be improved growth and fewer side effects.

This is significant because orthotopic liver transplantation is usually more successful in infants who weigh more than 10 kg at the time of surgery (liver transplantation is a reality for the pediatric patient with severe liver disease).

Unfortunately, timely recognition serious illness liver in a pediatric patient remains a serious problem. One contributing factor is that liver damage in a pediatric patient has a limited number of manifestations.

Consequently, different 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 document a number of factors contributing to late referral of children with liver disease (Table 1).

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

Lack of follow-up of 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 the presence of pigmented stools

ETIOLOGY

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

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

NEWBORN AND INFANTS

Cholestatic disorders

- Biliary atresia
- Common bile duct cyst
- Insufficiency of intrahepatic bile ducts (eg Allagile syndrome)
- Syndromes of progressive familial intrahepatic cholestasis (Byler disease and syndrome)
- Benign recurrent intrahepatic cholestasis (Caroli disease and syndrome)
- Thickening of bile (S/P hemolytic disease)
- Cholelithiasis
Idiopathic neonatal hepatitis and diseases that mimic 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-Barra virus
- Parvovirus B19
- Rubella
- Reovrus - type 3
- Adenovirus
- Enterovirus
- Syphilis
- Tuberculosis
- Toxoplasmosis
Metabolic disease
- Peroxysmal dysfunction (Zellweger syndrome)
- Disorders of bile acid metabolism
- Urea cycle disorders (arginase deficiency)
- Disorders of amino acid metabolism (tyrosinemia)
- Lipid metabolism disorders (Niemann-Pick type C/Gaucher/Wolman)
- Disorders of carbohydrate metabolism (galactosemia, fructosemia, glycogen storage disease type IV)
Toxic/pharmacological damage (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. In contrast, alcohol or acetaminophen intoxication and Wilms disease are typical in older children, especially adolescents.
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 of various causes leading to liver disease in children are extremely long, about 10 diseases account for approximately 95% of all cases of cholestasis observed, and of these, biliary atresia and neonatal hepatitis are responsible for more than 60%.
Typically, the clinician first suspects liver disease in a newborn who presents with classic signs such as persistent jaundice, hepatomegaly, coagulopathy, or weight loss.
In other cases, it is the accidental discovery of abnormalities during serum testing.
Jaundice, confusion, and coma occur in older children and adolescents with acute hepatitis or after exposure to the toxin. Itching observed in older children may be considered 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 baby older than 14 days to one of these causes.
Jaundice in any infant over 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 dietary changes may raise suspicion for an inborn error 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 girls of normal weight, and the rate of intrafamilial recurrence approaches zero. Also, the concomitant syndrome of polysplenia speaks in favor of the diagnosis of biliary atresia.
Patients with biliary atresia have earlier onset of jaundice and acholic stools compared with those with neonatal hepatitis.
In cholestatic disease, jaundice is almost invariably noted in the first month of life.
Acholic stool is also highly characteristic of cholestasis in infancy. When extra or intrahepatic obstruction is present, little or no bilirubin is released into the intestine, resulting in uncolored, unformed fecal material.
Although some pigment may be present in the stool of newborns with biliary obstruction due to desquamation of pigment-containing cells into the stool.
Moreover, the disintegration of the stool into pieces usually shows that the pigment is only superficial, with the interior being at best the color of clay.
Maternal fever or other signs of infection raise suspicion of sepsis as the underlying cause of jaundice in the newborn. Gram-negative bacteria (eg E coli) that cause urinary tract infections are particularly 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 elevated aminotransferases in the absence of any known exposure to hepatotoxic substances. Hepatitis A often has an anicteric form in children under 5 years of age and is often not recognized.
Evidence of liver disease in patients who have received tattoos, who have used intravenous drugs, or in whom any disease has resulted in increased exposure to parenterally administered blood products (hemodialysis, hemophilia, surgery) before widespread screening (1992) may raise suspicion for infection hepatitis C.
Adolescents who develop jaundice should be asked confidentially about intravenous drug use, pure cocaine exposure, and intranasal use, which may be associated with hepatitis C (and possibly hepatitis B) infection.
If confirmed hepatitis B infection is particularly severe, co-infection or superinfection with hepatitis (D) delta should be suspected.
It is always important to obtain data on exposure to potentially hepatotoxic drugs, including isonazid, nitrofurantoin, sulfonamides, and nonsteroidal anti-inflammatory drugs such as acetaminophen and ibuprofen.
If overdose or intoxication causes liver dysfunction, children may experience altered mental status and even coma.
Confusion and coma raise suspicion of hepatic failure or metabolic disease leading to hyperammonemia, hypoglycemia, or 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.
A history of colic in the upper right quadrant and nausea (especially after eating fatty foods) indicates gallbladder disease, which is more common in older children.
Signs and symptoms of obesity from cardiac, endocrine, or intestinal disease should be considered, since serum aminotransferase abnormalities may reflect liver damage secondary to systemic disease (the liver as an "innocent bystander").
Increased concentrations of aminotransferases (especially AST) may also be a manifestation muscle disease.
Older children and adolescents with liver disease may initially complain of anorexia, fatigue, and jaundiced sclera.
Cholestasis can lead to complaints such as pruritis and especially dark and foamy 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, thereby creating visible foam.
PHYSICAL MANIFESTATIONS
Common physical findings associated with specific liver diseases are listed in Tables 3-6.
Table 3.
Diseases causing jaundice/increased 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-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

Bile flow malformations

- Atresia/insufficiency of intrahepatic bile ducts, non-syndromic and syndromic (Allagile syndrome)
- Cystic malformations: common bile duct cysts, cystic dilatation of intrahepatic bile ducts (Caroli disease), congenital hepatic fibrosis, polycystic liver and kidney disease.
OLDER AND GROWN CHILDREN

Acute viral hepatitis (HAV)

Hereditary diseases:

Wilson's disease
cystic fibrosis,
hepatic porphyrias,
Dubin-Johnson syndrome
Rotor syndrome

Malignant diseases:

leukemia,
lymphoma,
liver tumors

Chemical substances:

hepatotoxic drugs,
toxins (intestinal hydrocarbons, 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 plethora 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 contour, body habitus, or displacement of the liver margin by adjacent organs or external or internal neoplasms.
Therefore, measuring liver width is a useful adjunct to palpation at initial presentation and follow-up.
Liver width 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 the age of 1 week 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 epigastric region means either the presence of cirrhosis or the Riedel's lobe (normal anatomical elongation of the right lobe, which can be mistaken for hepatomegaly).
Table 4.
Diseases causing hepatomegal

BABIES AND CHILDREN
Storage diseases

-Acute: Reye's syndrome (fat)
- Chronic: glycogenosis, mucopolysaccharidosis, Gaucher disease, Niemann-Pick disease, gangliodidiasis, Wolman 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
- metastatic: neuroblastoma, Wilms tumor, gonadal tumors.
Table 5.
Diseases that cause liver failure
NEWBORN AND INFANTS

Infections:

herpes viruses,
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 TEENS
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
BABIES
Microcephaly:
congenital cytomegalovirus,
rubella,
toxoplasmosis
Characteristic face type:
arteriohepatic dysplasia (Allagile syndrome)
Cataract:
galactosemia
Retinal pigmentation: Allagille syndrome
Abnormal findings on pulmonary ascultation: cystic fibrosis.
Neuromuscular disorders (tremor, lethargy): lipid storage disease, Wilson's disease, oxidative phosphorylation disorders
CHILDREN
Prurith:
chronic cholestasis
Hemangiomas:
hemangiomatosis of the liver
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 in 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 insult with dilatation of the Glisson capsule due to edema, which is responsible for the perceived pain localized to the liver.

Severe hepatosplenomegaly indicates a storage disease or malignant disease, although particularly striking hepatomegaly itself is associated with significant hepatic fibrosis

At this state 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 identify vascular bruising caused by anatomical vascular malformations or increased blood flow to the liver.

Ascites suggests increased portal venous pressure and deterioration of hepatic function.

Certain physical signs raise significant suspicion for specific liver diseases. In neonates 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 typically have a characteristic facial pattern (beaked nose, high forehead, butterfly-shaped vertebrae, and a murmur on cardiovascular auscultation due to peripheral pulmonary stenosis and posterior embryotoxin due to ophthalmological examination.

The presence of recurrent vomiting in a newborn, especially if it is unremitting, may indicate an inborn metabolic disorder, which is also usually 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 would raise suspicion for 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 damage to 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 removed through bile usually increase in cholestatic conditions. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), and conjugated bilirubin (all requiring a clear biliary tree for elimination) are usually elevated.

Conversely, hepatocyte necrosis following viral or toxic liver insult (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 levels of GGT and AP do not increase 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 toxic accumulation of bile within the hepatocytes and biliary tree. In hepatocellular disease, reduced bile flow (sludge) that results from hepatocyte necrosis also causes a mild 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 interpreting a set of clinical and laboratory criteria, including liver biopsy. This is especially true for newborns and infants, where there is 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 in whom the presence of jaundice after 14 days of life requires evaluation. Table 7 shows the goals of the stepwise assessment of infants with jaundice.

Table 7.
Objectives of the stepwise assessment of infants with jaundice
Recognize cholestasis (unconjugated or physiological hyperbilirubinemia)
Assess the severity of liver damage
Separate specific disease 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. Rapid evaluation is offered for infants who present 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 assessment (family history, feeding history, physical examination)
- Fractionation of serum bilirubin and determination of serum bile acid levels
- Stool color assessment
- Hepatic synthetic function index (prothrombin and albumin time)

Recognize specific disease entities
- Viral and bacterial cultures (blood, urine, cerebrospinal fluid)
- Hepatitis B surface antigen and other viral titers and syphilis titers (VDRL) in selected patients at risk
- 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 content
- Liver biopsy

Liver function tests

Because the liver has a large functional reserve, abnormal laboratory values are often the only manifestation of overt liver disease and may be present long before overt clinical manifestations. In a typical scenario, a doctor who suspects liver disease will usually order "Liver function tests" (LFTs) to evaluate liver function. Consistent monitoring of these indicators can provide information about prognosis, response to therapy, and degree of dysfunction.

However, the term LFT is not entirely accurate because only two of the parameters commonly obtained are true measures of liver function—prothrombin time (PT) and serum albumin levels—both of which assess synthetic capacity. All of the other parameters - essentially indirect indicators liver function, and many of these parameters are altered in situations other than liver disease. For example, elevated aspartate aminotransferase (AST) is associated with 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 involves 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 neurogenesis deficiency. Increased anion shift in metabolic acidosis also suggests organic acidemia. Hypo- and hyperthyroidism may be associated with jaundice. Sweat chloride testing may be necessary 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 is usually helpful in excluding the possibility of an inborn error of bile acid metabolism. Urinary succinylacetone levels may indicate the presence of tyrosinemia. A urine test and culture should always be obtained in any child with jaundice because 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.
The healthy mature liver removes unconjugated bilirubin from the blood and mediates the conjugation of unconjugated bilirubin with two glucuronic acid molecules. Bilirubin conjugation converts an essentially fat-soluble substance (unconjugated bilirubin) into a water-soluble substance (conjugated bilirubin) that can be excreted 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.

Physiological neonatal jaundice (in which unconjugated bilirubin levels increase) results from immaturity of the glucuronyl transferase system responsible for bilirubin conjugation. Jaundice associated with breastfeeding(slight temporary decrease in conjugating 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, inborn errors of bilirubin metabolism (eg, Crigler-Najar types 1 and II), and thyroid dysfunction. Unconjugated hyperbilirubinemia of extreme degrees may be associated with kernicterus in a newborn.
If conjugated (direct, bound) bilirubin is present, evaluation must be aggressive. Serum conjugated bilirubin is 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 bilirubin production (eg, as a result of hemolysis) or a decreased ability of the liver to bind bilirubin. The conjugated fraction is associated with severe 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 urobilinogen is excreted in the stool as coprobilinogen; 20% undergoes enterohepatic recirculation. Only a small fraction ends up in the urine, but it increases in the presence of hepatocellular damage due to decreased hepatic 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 into urobilinogen. Interestingly, delta-bilirubin, due to its covalent binding to albumin, is not excreted in urine, and therefore tends to remain elevated in the serum for some time after the initial cholestatic insult, 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 tests of hepatocyte necrolysis. Significant increases in these enzymes, which are released from damaged hepatocytes, indicate hepatocellular damage. Slightly abnormal levels may also be associated with cholestatic processes, since reverse flow 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 to 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 in low concentrations in other tissues (eg, muscle). Conversely, AST is found in high concentrations in many tissues, including cardiac and skeletal muscle, kidney, pancreas, and red blood cells. A coenzyme of both enzymes is vitamin B6, so persistently abnormally low AST and ALT values suggest an underlying vitamin B6 deficiency.

In general, aminotransferase levels do not provide diagnostic information, but particularly high levels suggest drug hepatotoxicity (eg, acetaminophen overdose), hypoxia/shock, and viral hepatitis. These levels still do not have prognostic value; patients with very high abnormal values may do well, especially in cases of acetaminophen toxicity. However, they are useful in monitoring a patient's clinical progress; for example, progressively decreasing AST/ALT values in a young patient who has HAV infection and is otherwise well is a reassuring sign that the liver disease is resolving. Conversely, decreasing AST/ALT values in the presence of a shrinking liver, increasing PT partial thromboplastin time (PTT) and lack of clinical improvement are an ominous sign. This suggests a reduced functioning hepatocyte mass due to necrosis, which has reduced the number of enzymes available for release into the circulation.

Levels alkaline phosphatase(AP)
AP is located primarily in the canalicular membrane of liver cells, therefore, elevated serum AP levels usually indicate obstructive liver disease (eg, bile duct obstruction). However, AR is found in other tissues, including bone, kidney, and small intestine. High performance ARs are typically found in children during periods of accelerated growth, such as the pubertal growth spurt. Particularly high levels should lead to suspicion of possible bone pathology (eg, rickets), especially if the 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 AR values 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 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 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. 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 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 normal cholic and chenodeoxycholic acids. The interpretation of elevated serum bile acid levels in neonates and infants is complicated by the presence of relative "physiologic 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 metabolite precursors makes it possible to identify specific inborn errors of bile acid metabolism. With recent technological advances such as fast atom bombardment mass spectrometry, it is possible to rapidly analyze urine samples from individuals suspected of having specific bile acid disorders and to identify specific inborn errors of bile acid metabolism, such as 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 are 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 AP) 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; such rates in this age group are usually up to 8 times higher than rates observed in adults. Finally, GGT values may be elevated in response to various pharmacologic 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 rough endoplasmic reticulum of healthy hepatocytes, may suggest decreased production due to decreased liver function following hepatocellular disease. However, low albumin concentration is a late manifestation of liver disease. When present, it raises the suspicion of a chronic disease. Undoubtedly a sharp decline albumin in a patient with long-standing disease is particularly concerning, 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 colonic bacteria on proteins in the diet, and the liver plays a major role in its elimination. Of course, 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 quickly transported to the laboratory on ice - sharply elevated ammonia levels may be obtained).

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

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

Trace elements and vitamin-related disorders
Copper accumulates in the liver during cholestasis because it is excreted primarily through 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 eliminating manganese supplements in total parenteral nutrition solutions used for patients with liver disease.

Aluminum is also excreted through biliary excretion and is hepatotoxic in high doses. Cholestasis can lead to its accumulation 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 into the intestines, malabsorption of fat-soluble vitamins occurs. Moreover, esters of vitamins A and E 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 necessary to metabolize vitamin D into its active form. Of course, impaired hepatic function usually reduces vitamin D levels, and rickets is common among children with cholestasis.

IMAGING AND HISTOPATHOLOGY OF THE LIVER AND BILIARY TRACT

Abdominal ultrasonography -
is relatively inexpensive, easy to perform, and can usually be attempted without sedating the patient. It allows you to measure liver size, confirm changes in liver structure and the presence of cystic or non-cystic parenchymal lesions. Common bile duct cysts and stones can be detected with 95% accuracy. Ultrasonography is also useful as a screening method for liver space-occupying lesions 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 radiolabeled N-substituted imino-diacetate (IDA) atoms labeled with technetium-99, such as diisopropyl-IDA (DISIDA) or para-isopropyl-IDA (PIPIDA), is used in the evaluation 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 tracer in the intestine may not represent an obstructive defect, but rather a parenchymal disease process in which the uptake or concentration of the tracer is poor. To ease bile flow, patients are often given phenobarbital (5 mg/kg per day, divided into 2 daily doses) for 3-5 days before undergoing the 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 the evaluation of neonatal cholestasis. This time-consuming process can potentially delay diagnosis. Moreover, it has high false-positive (i.e., no excretion) and false-negative (i.e., apparent excretion of the labeled atom) rates (at least 10%) and is not very effective when serum bilirubin levels are elevated. . A 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-line methods for diagnosing liver disease in children. However, they can be useful in specific situations. CT scanning of the liver can reveal deposits of glycogen, iron and lipids within the liver parenchyma and can clearly identify and characterize liver neoplasms. However, CT is more expensive and technically more difficult in infants than ultrasonography and exposes the patient to ionizing radiation. MRI has comparable sensitivity to CT in recognizing chemical differences in tissue and identifying 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 -
a cardinal method for quickly arriving at a diagnosis of the underlying liver disease. Fast, safe and effective technique usually does not require the patient to stay in the operating room or be 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 whether there is any storage disorder: confirm the presence of Wilson's disease (copper storage), glycogen storage disease or neonatal iron storage disease, as well as many other pathological conditions. Tissue histology 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, thereby eliminating the risk of subjecting a child with cholestasis caused by intrahepatic bile duct insufficiency to unnecessary surgery.

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 due to viral hepatitis acquired in utero or postnatally.

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

For example, homozygous alpha-1 antitrypsin deficiency, which is now recognized as a specific cause of liver disease in newborns, 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 considered 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 ineffective 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 be present 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 levels are elevated and more than 50% of the indicator is due to the conjugated fraction. Aminotransferase levels are almost always elevated, but to varying degrees. AR and GGT levels, if elevated, are only moderate.

Serum albumin and PT may be abnormal, and the degree of abnormality correlates with the severity of the disease at initial presentation. Ultrasonography usually shows the presence of the gallbladder and the absence of cystic malformations of the biliary tree to explain cholestasis. Hepatobiliary scintigraphy reveals delayed radionuclide transport and ultimately shows a patent extrahepatic biliary tree.

A severely damaged liver may have difficulty taking up the radionuclide, reducing the usefulness of this test in severely ill children. Liver biopsy usually provides a definitive diagnosis by demonstrating transformation of giant cells with portal inflammatory infiltrates and absence of bile duct proliferation.

Management of these children involves supportive measures and avoiding the consequences of malabsorption by ensuring adequate nutrition and intake of fat-soluble vitamins and medium-chain triglycerides until recovery (which occurs in the majority). Liver transplantation is an alternative for those who do not respond to 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 common indication for liver transplantation in infants and children.

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

Since cirrhosis develops quickly, surgical correction Biliary atresia is most effective if performed before the age of 3 months, which emphasizes the need for rapid and accurate diagnosis of the cause of liver dysfunction observed in an infant. As with idiopathic neonatal hepatitis, children with biliary atresia are admitted 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 uptake of the labeled atom and no excretion into the intestine even after 24 hours. A liver biopsy confirms the diagnosis - it reveals proliferation of interlobular bile ducts, periportal fibrosis and bile plugs in the tubules.

Liver transplantation may be necessary if there is progressive hepatic decompensation, refractory growth failure, synthetic dysfunction, and the development of coagulopathy or intractable portal hypertension with recurrent gastrointestinal bleeding or hypersplenism.

Other reasons

Other disease entities leading to liver dysfunction in the newborn and infant can be diagnosed through a combination of general examinations.

Structural abnormalities of the biliary tree, such as congenital hepatic fibrosis or choledochal cysts, are usually detected by ultrasonography. Liver biopsy shows a characteristic "ductal plate defect" in infants with congenital hepatic fibrosis.

Bacterial infections causing cholestasis can be identified by a positive blood or urine culture. A history of maternal contact with or past infection (toxoplasmosis, syphilis, cytomegalovirus, herpes simplex virus, varicella and other viruses) should prompt testing for these infections. In cases of 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 disturbances of hepatic synthetic function, mild deviations in the levels of bilirubin, transaminases and rickets

The presence of succinyl acetone in the 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 protein inhibitor ZZ (PiZZ) typing and is usually confirmed by characteristic periodic acid Schiff-positive alpha 1-antitrypsin granules deposited within the hepatic parenchyma on liver biopsy.

Excessive iron deposits are observed on biopsy in infants with neonatal iron storage disease. Congenital hypothyroidism, which may manifest as unclear hyperbilirubinemia, is excluded by assessing thyroid function.

LIVER DISEASES IN AN OLDER CHILD

The main causes of liver disease observed after infancy are toxic, infectious, metabolic, autoimmune, vascular and infiltrative. The relative frequency of each disorder varies depending on the age of the patient. Viral hepatitis occurs in patients of all ages, as does liver disease caused by cardiac or collagen vascular disease. Disorders of fat metabolism are observed in older infancy and early childhood. Wilson's disease is usually detected in late childhood or adolescence.

Acute hepatitis

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

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. Diagnosis of acute infection is based on the presence of anti-HAV IgM antibodies in serum.

Hepatitis B virus (HAV) infection can cause both acute and chronic hepatitis and the development of 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 been rarely described. The diagnosis is based on the detection of anti-HCV antibodies and is confirmed chain reaction polymerase 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.

Hepatitis E virus (HEV) occurs as an epidemic in parts of the world with poor sanitary conditions. Cases diagnosed in North America were in patients who brought the virus from abroad. It can be a particularly devastating disease 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 even within 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 viral infection, an autoimmune process, exposure to hepatotoxic drugs, or cardiac metabolic or systemic disorders.

Autoimmune hepatitis (AIH)

AIH is an 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: AIH type I is more common in women and is characterized by positive antinuclear antibody, and AIH type II 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. AP and GGT values are usually normal or only slightly elevated. Liver biopsy reveals inflammatory infiltrates 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 (without signs of an underlying disease and unknown etiology) and is usually associated with inflammatory bowel disease. Secondary sclerosing cholangitis occurs as a result of stones, postoperative strictures, or tumors.

Children may have jaundice, pruritis (itching) or fatigue when presenting. Elevated AR levels are very common, but there is no specific marker of the disease. Biopsy shows typical concentric fibrosis around the interlobular bile ducts ("onion skin" appearance). Cholangiography or endoscopic retrograde cholangiopancreatography is necessary to make the diagnosis.

Treatment involves 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 necessary 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 clinicopathologic presentation can be extremely variable, Wilson's disease should be included in the differential diagnosis of any child presenting with liver disease, neurologic abnormalities, behavioral changes, or Kayser-Fleischer rings.

Serum ceruloplasmin, a copper carrier, is usually, but not always, low. Definitive diagnosis requires assessment of 24-hour urinary copper excretion and quantification of copper in biopsied liver tissue.

Wilson's disease may present as fulminant liver failure, usually in association with hemolytic crisis due to toxic effects copper on red blood cells.

Therapy is penicillamine, which allows copper to be excreted into the urine. Because 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. Aminotransferases are usually 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 being affected as an “innocent bystander” to 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 insult without increasing coagulopathy or hyperbilirubinemia.

Infiltrative liver disorders are observed with leukemia, lymphoma and neuroblastoma , but these nosological units are usually quickly identified. Similarly, primary liver tumors are easily identified in a child who presents with hepatomegaly or abdominal distension. Less commonly, children initially present with jaundice and weight loss.

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

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

CONCLUSION

Identifying serious 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.
An advancement is the availability of numerous treatment options for liver disease other than transplantation (Table 9).

Table 9
Options for children with liver disease beyond transplantation

Replacement of the deficient abnormal end product, such as oral administration of primary (essential?) bile acids (in patients with disorders of bile acid biosynthesis)
Reduction of accumulated substances (eg, antioxidant cocktails and binding in neonatal iron storage disease)
Use of metabolic inhibitors (eg, NTBC for tyrosinemia)
Enzyme induction (eg, phenobarbital in Crigler-Najjar syndrome type II)
Substrate restriction in the diet (e.g. galactose for 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, definitive therapies such as targeted enzyme replacement or gene therapy may be available for certain metabolic disorders. Given these exciting prospects, it is of utmost importance to correctly and promptly evaluate liver disease in children to enable them to grow and be as healthy as possible until they reach an age at which definitive therapy may 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

Diseases in children associated with abnormal liver function can occur for various reasons. In any case, they pose a serious threat to the health and development of the child.

Liver diseases cannot always be detected immediately, since the symptoms of most childhood diseases are similar in the initial stages. The obvious symptom is jaundice. Timely detection of this type of deviation in a child is especially important, as it will give a chance to get rid of the ailment with the least complications.

Causes of liver disease in children

Deviations in the functioning of this organ in children can occur for the following reasons:

The following deviations should attract the attention of parents:

Symptoms of the disease are yellowing of the skin and whites of the eyes.

Yellowing of the skin and whites of the eyes;
Complaints of pain in the right side;
Temperature increase;
Lack of appetite;
Drowsiness and decreased activity;
Nausea, vomiting;
Intestinal upset;
The chair is white;
Darkening of urine.

Symptoms can be smoothed out, especially in the presence of colds. This can even confuse a doctor. As a rule, he prescribes urine and blood tests. Judging by the color of urine, one can even visually suspect a liver disorder in a child. A complete blood test will show the level of bilirubin, a dye produced by the liver. The hemoglobin level in a healthy child is normal or slightly low. With hepatitis, the hemoglobin content is increased. Blood clotting also depends on the condition of the liver. Decreased clotting may be a sign of disease. The number of red blood cells and platelets also changes. After studying the test results, the doctor decides whether to refer the child for a more complex examination. A urine test will show the concentration of bilirubin, the presence of toxic compounds, and an increased content of leukocytes, indicating an inflammatory process.

Liver diseases possible in children

Liver diseases of varying severity can occur in children of any age. Such forms of abnormalities as neonatal jaundice and moderate hepatomegaly may have physiological causes. Severe lesions can occur with the following diseases:

Due to the natural underdevelopment of the bile ducts, which is possible during the prenatal period, the liver of newborns may not immediately adapt to normal conditions. So-called physiological jaundice appears. The cause of yellowing of the body and eyes in newborns may be breastfeeding if the mother has fatty milk. Usually, until two weeks of age, this jaundice does not pose a danger and goes away on its own. If jaundice does not go away after 2 weeks, then the cause may be a disease. The child must be examined and, if the disease is confirmed, treated, paying attention to the slightest changes in condition. The complication can be very dangerous, as it usually occurs suddenly (it is also called “kernicterus”) and leads to the death of the child.

Severe form of jaundice in newborns - “kernicterus”

Sometimes the cause of jaundice in a child may be a hereditary disorder of bile circulation in the body (familial cholestasis). Most often this disease occurs at the age of 1 month. A sign of insufficient bile formation is white stool of heterogeneous composition with brown spots.

Severe diseases in infants include biliary atresia - obstruction of the biliary tract. This disease has practically no cure; a liver transplant is required. A difficult operation can have life-threatening complications (cirrhosis and others).

Deviations can also occur if a woman takes medications, alcohol, or smokes during pregnancy or breastfeeding. The child may get toxic hepatitis.

Diseases in older children

A common disease in adolescent children is toxic damage to the liver tissue, which occurs due to alcohol consumption, drug addiction and other bad habits.

Infection with viral hepatitis A or B may occur through sharing dishes or hygiene items with a sick relative. Infection with viral hepatitis C can be the result of accidental contact with the blood of virus carriers on medical instruments in the dentist's office, and can also occur during surgical operations or intravenous drug infusion. Acute manifestations include jaundice, itchy skin, hepatomegaly, fatigue, nervous disorders, including loss of consciousness and coma. If a child is suddenly losing weight, has stomach pain on the right side, has nausea and vomiting, then he must be seen by a doctor as quickly as possible.

If you suspect a disease, urgent examination by laboratory methods

This organ may be affected by tumors of benign or malignant origin. Severe forms of liver tissue damage are cirrhosis and cancer. The cause of such ailments can be a complication of chronic viral hepatitis.
A particularly severe form is. In children, it can be congenital and becomes fully apparent by the age of 2-3 years. The liver tissue cells atrophy and the child dies. In older age, symptoms of liver failure are manifested by an enlarged abdomen due to the accumulation of fluid in the abdominal cavity, swelling, decreased blood clotting, and signs of poisoning.

Diagnosis and treatment of liver diseases in children

The following methods of treatment of childhood liver diseases are available:

Conservative – with the help of medications and diet;
Surgical – bloodless operations on the liver tissue and biliary tract (laparoscopy), as well as in the most severe cases, operations with opening of the abdominal cavity (for example, liver transplantation).

All operations on children are performed under full anesthesia.

Timely diagnosis and treatment, even in severe cases, can restore the child’s health and sometimes save a life.

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Everyone understands that without normal healthy liver a person cannot fully exist. That is why parents have many questions regarding the increased size of this organ in children. What to do if a child has an enlarged liver, you will learn from this article.

Liver sizes are normal

The size of the liver is usually determined by three parameters: on the right along the areola line, on the left along the oblique line and along the midline of the chest. You can see how the lines go in the figure. The normal sizes of the liver in a healthy child are:

Up to 3 years - on the right along the isola line - 5 cm, on the midline - 4 centimeters, and on the left oblique line - no more than 3 centimeters.
Up to 7 years - on the right along the isola line - no more than 6 centimeters, along the mid-sternal line - 5 centimeters, on the left oblique - no more than 4 centimeters.
Up to 12 years - on the right along the isola line - no more than 8 centimeters, on the midline - 7 centimeters, on the left oblique - 6 centimeters.
Over 12 years old - on the right along the areola line - 10 centimeters, along the midline - 9 centimeters, along the oblique left line - 8 centimeters.

In a healthy child, the liver should not normally be enlarged. Also, it should not extend beyond the costal arch.

The exception is newborns and children under 1 year of age. In them, such an extension beyond the costal arch can be a completely normal physiological phenomenon if the exit does not exceed 2 centimeters.

In children 5-6 years old, liver protrusion beyond the costal arch may also be present, however, it should not normally exceed 1 centimeter. Any deviations from the above norms are considered an enlargement of the liver and may indicate possible pathologies.

What do deviations mean?

An enlarged liver is not an independent disease, but only a symptom of some disease. The symptom itself is medically called hepatomegaly. Not every increase should be considered a warning sign. If the child is not yet seven years old, if his size is slightly increased, doctors do not consider this condition to require medical intervention.

If the size of the liver is significantly increased or hepatomegaly is first detected after the age of seven, this symptom will be regarded as pathological, and the doctor will direct all efforts to find the real reason liver enlargement.

A vital organ can “grow” in size due to congenital pathologies:

intrauterine infections;
viral diseases that affected the fetus during pregnancy (primarily rubella, toxoplasmosis and cytomegalovirus);
congenital absence or fusion of the bile ducts (artresia);
diseases of the cardiovascular system, during which one or another degree of heart failure develops;
hemolytic disease that occurred to the fetus during pregnancy due to Rh conflict with the mother, as well as a disease that “started” after the birth of the child for the same reason (usually happens to Rh-positive babies born from Rh-negative mothers );
numerous cysts;
hereditary diseases of the blood circulation and blood vessels, in which the vessels dilate pathologically, which is accompanied by spontaneous bleeding.

The liver can also enlarge for other reasons that are not congenital:

Infectious mononucleosis;
viral hepatitis;
severe toxic poisoning from poisons or chemicals;
inflammation of the gallbladder;
tuberculosis;
syphilis;
obesity and metabolic diseases;
diabetes;
oncological diseases and blood diseases (lymphoma, leukemia, etc.).

Can lead to an increase in liver size violations of the principle of balanced baby food, especially if carbohydrates and fats predominate in the baby’s diet, and proteins are insufficient. If the pathology has congenital causes, then it can usually be established in the first year of the baby’s life, because the pediatrician during the examination will not be able to help but notice that the size of the liver is exceeded upon palpation. Pathological changes of an acquired nature are usually diagnosed later, closer to 5-7 years.

Since the list of possible causes is extremely wide, it is better not to try to find out the true one on your own.

Hepatomegaly - a syndrome that cannot be ignored, because not only the health of the baby in the future, but also his life depends on how quickly and correctly the child receives qualified assistance.

Signs of pathologies

It is clear that parents cannot independently measure the baby’s liver to understand whether he has any abnormalities. But any mother can suspect something is wrong based on a number of signs that may indirectly indicate liver problems:

the child often complains of heaviness in the abdomen, while the upper part of the abdomen on the right is somewhat painful when lightly pressed with the hand;
the skin has a yellow or yellowish tint, the eyeballs turn yellow;
the baby develops problems with nutrition - lack of appetite, nausea and vomiting, stool instability, frequent diarrhea;
feces become very light, sometimes almost white, and urine, on the contrary, darkens;
prolonged jaundice of newborns (if more than two weeks have passed since discharge from the maternity hospital, and the baby is still yellow, this is a reason to check the liver);
characteristic bitter odor from the mouth (not a mandatory sign!).

Where to contact?

If parents suspect that their child has liver problems, they should definitely visit a pediatrician with their child. Of course, a specialist such as a hepatologist will be able to understand the problem much faster, but there are not many doctors with such a rare and narrow specialization in Russia, and they are not accepted in every clinic.

If you have the opportunity to visit such a doctor, then it is better to do so. If there is no hepatologist, a pediatrician and gastroenterologist will help. In such a duet, two specialists will definitely find pathological causes, if they exist, and will be able to prescribe adequate treatment. Delaying the start of the examination is strictly prohibited. Any problems with the liver, and an increase is also considered a problem, increases the likelihood of intoxication. After all, the natural, nature-created “filter” of the body - the liver - does not function fully.

Usually, an experienced pediatrician can determine whether a child’s liver and spleen are enlarged using his hands - by palpating and tapping the liver area. Suspicions are confirmed by ultrasound diagnostics.

An ultrasound can show not only the exact size of the liver (down to millimeters), but also possible changes in its tissues, disturbances in the right or left lobe.

Treatment

For children under 7-8 years of age, a slight enlargement of the liver (just over 2 centimeters) is corrected with the help of medications. Surgical intervention is permissible only in cases of gross and severe congenital liver lesions associated with structural anomalies. Treatment always begins with treatment of the underlying identified disease. If a viral infection is to blame, the child may be hospitalized and given a course of effective antiviral drugs in a hospital setting ( "Tamiflu"). Such drugs are not prescribed at home, but antiviral drugs are available to everyone from the pharmacy ( "Anaferon" and others) are not officially considered effective and influence the course of a viral infection.

Bacterial infections or diseases with associated inflammatory processes are usually treated with antibiotics, choosing the least severe ones so as not to put additional drug “pressure” on the liver. Metabolic diseases are treated by an endocrinologist using special medications that improve and normalize metabolic processes. Simultaneously with the treatment of the underlying disease, a child with an enlarged liver is prescribed special hepatoprotective therapy. It includes products whose task is to support the already suffering liver during the drug load.

Typically, liver maintenance therapy includes drugs such as "Essentiale", "No-shpa", "Karsil", "Heptral" And "Duspatalin". Among the hepatoprotectors most often prescribed in childhood are: "Galsten", "Ursosan", "Holenzym".

In order for the child’s body to work better, during the treatment process, medications are prescribed that contain important enzymes, which, due to pathology, may be produced in insufficient quantities. Such drugs include "Creon","Mezim".

You should not take enzymes for too long, so as not to “spoil” the child’s body. Otherwise, it will reduce the production of its own enzymes to nothing, which will then lead to very disastrous consequences.

The child, regardless of the reason that led to hepatic enlargement, appointed special diet . Fatty foods - butter, lard, cheeses with a high percentage of fat, full-fat milk and sour cream - are completely removed from the child's menu for a long period of time. For a baby with hepatomegaly, cocoa, chocolate, eggs, mushrooms, nuts, fatty meat, acidic drinks, including fruit juices, canned food and smoked meats, spices and even ice cream are strictly prohibited. Sticking to a diet is very important, otherwise treatment may be ineffective despite taking prescribed medications. The child needs low-fat varieties meat, vegetables, steamed and baked food. Fried foods and fresh baked goods should be avoided. You need to eat fractionally, at least 5 times a day in small portions.

No doctor will give forecasts in advance for the treatment of an enlarged liver, because the outcome of the pathology is influenced by many things - the underlying disease, the state of the baby’s immunity, and the degree of enlargement of the liver itself. However, timely treatment and quickly started treatment, according to Ministry of Health statistics for 2016, provide a favorable prognosis in more than 90% of cases.

It is most difficult to predict an increase in liver disease if it is caused by toxic poisoning, as well as complicated by the onset of cirrhosis. Such problems are much more difficult to treat, but even here the positive outcome is estimated at more than 60%.

A mother can protect her child from liver problems even during pregnancy. If she pays close attention to her health and protects herself from infections and viruses, then the chances of pathological changes in the development and functioning of the digestive organs in the baby’s body will be minimal.

A child 2 years old, like a child 3-4 years old and older, should not have an abundance of fatty and carbohydrate foods on the table, especially with a sedentary lifestyle. A passion for fast food at an older age - at 8-10 years old - can also lead to fatty liver, and this will be quite dangerous, since such an increase will never be considered physiological. There is only one piece of advice - you need to be careful about your child’s nutrition. No decoctions or pills should be given to a child to prevent liver problems! If you have problems, you need to go to the doctor. If not, that's enough healthy eating, active leisure, sports, so that you don’t need to “clean” anything.

See the following educational video for all about liver size.

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

Early recognition is especially important in neonates and infants, as delay in diagnosis can have a negative impact on prognosis.

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

Unfortunately, timely recognition of severe liver disease in a pediatric patient remains a serious problem. One contributing factor is that liver damage in a pediatric patient has a limited number of manifestations.

Consequently, different disorders often have virtually identical initial manifestations.

Table 1

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

Lack of follow-up of 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 the presence of pigmented stools

ETIOLOGY

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

Table 2.

The most common causes of liver disease in children of different 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 disease and syndrome)

Benign recurrent intrahepatic cholestasis (Caroli disease and syndrome)

Thickening of bile (S/P hemolytic disease)

Cholelithiasis

Idiopathic neonatal hepatitis and diseases that mimic 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-Barra virus

Parvovirus B19

Rubella

Reovrus - type 3

Adenovirus

Enterovirus

Syphilis

Tuberculosis

Toxoplasmosis

Metabolic disease

Peroxysmal dysfunction (Zellweger syndrome)

Bile acid metabolism disorders

Urea cycle disorders (arginase deficiency)

Disorders of amino acid metabolism (tyrosinemia)

Lipid metabolism disorders (Niemann-Pick type C/Gaucher/Wolman)

Disorders of carbohydrate metabolism (galactosemia, fructosemia, glycogen storage disease type IV)

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

Tumors (intra- and extrahepatic)

OLDER CHILDREN AND TEENS

Viral hepatitis (hepatitis B virus, hepatitis C virus)

Autoimmune hepatitis

Toxic

Pharmacological (eg acetaminophen)

Liver disease associated with chronic inflammatory bowel disease, sclerosing cholangitis

Toxins and pharmacological agents

Malignant diseases

Wilson's disease

Blockage of hepatic veins

Fatty liver infiltration during pregnancy

Fatty infiltration of the liver in obesity (non-acholic steatohepatitis)

Hypotension/ischemia/heart failure

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

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

Typically, the clinician first suspects liver disease in a newborn who presents with classic signs such as persistent jaundice, hepatomegaly, coagulopathy, or weight loss.

In other cases, it is the accidental discovery of abnormalities during serum testing.

Jaundice, confusion, and coma occur in older children and adolescents with acute hepatitis or after exposure to the toxin. Itching observed in older children may be considered 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 baby older than 14 days to one of these causes.

Jaundice in any infant over 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 dietary changes may raise suspicion for an inborn error 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 girls of normal weight, and the rate of intrafamilial recurrence approaches zero. Also, the concomitant syndrome of polysplenia speaks in favor of the diagnosis of biliary atresia.

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

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

Acholic stool is also highly characteristic of cholestasis in infancy. When extra or intrahepatic obstruction is present, little or no bilirubin is released into the intestine, resulting in uncolored, unformed fecal material.

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

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

Maternal fever or other signs of infection raise suspicion of sepsis as the underlying cause of jaundice in the newborn. Gram-negative bacteria (eg E coli) that cause urinary tract infections are particularly 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 elevated aminotransferases in the absence of any known exposure to hepatotoxic substances. Hepatitis A often has an anicteric form in children under 5 years of age and is often not recognized.

Evidence of liver disease in patients who have received tattoos, who have used intravenous drugs, or in whom any disease has resulted in increased exposure to parenterally administered blood products (hemodialysis, hemophilia, surgery) before widespread screening (1992) may raise suspicion for infection hepatitis C.

Adolescents who develop jaundice should be asked confidentially about intravenous drug use, pure cocaine exposure, and intranasal use, which may be associated with hepatitis C (and possibly hepatitis B) infection.

If confirmed hepatitis B infection is particularly severe, co-infection or superinfection with hepatitis (D) delta should be suspected.

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

If overdose or intoxication causes liver dysfunction, children may experience altered mental status and even coma.

Confusion and coma raise suspicion of hepatic failure or metabolic disease leading to hyperammonemia, hypoglycemia, or 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.

A history of colic in the upper right quadrant and nausea (especially after eating fatty foods) indicates gallbladder disease, which is more common in older children.

Signs and symptoms of obesity from cardiac, endocrine, or intestinal disease should be considered, since serum aminotransferase abnormalities may reflect liver damage secondary to systemic disease (the liver as an "innocent bystander").

Increased concentrations 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 jaundiced sclera.

Cholestasis can lead to complaints such as pruritis and especially dark and foamy 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, thereby creating visible foam.

PHYSICAL MANIFESTATIONS

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

Table 3.

Diseases causing jaundice/increased 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-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

Bile flow malformations

Atresia/insufficiency of intrahepatic bile ducts, non-syndromic and syndromic (Allagile syndrome)

Cystic malformations: common bile duct cysts, cystic dilation of intrahepatic bile ducts (Caroli disease), congenital hepatic fibrosis, polycystic liver and kidney disease.

OLDER AND GROWN CHILDREN

Acute viral hepatitis (HAV)

Hereditary diseases:

Wilson's disease

cystic fibrosis,

hepatic porphyrias,

Dubin-Johnson syndrome

Rotor syndrome

Malignant diseases:

leukemia,

liver tumors

Chemical substances:

hepatotoxic drugs,

toxins (intestinal hydrocarbons, 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 plethora 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 contour, body habitus, or displacement of the liver margin by adjacent organs or external or internal neoplasms.

Therefore, measuring liver width is useful additional method to palpation at initial presentation and follow-up.

Liver width 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 the age of 1 week 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 causing hepatomegal

BABIES AND CHILDREN

Storage diseases

Acute: Reye's syndrome (fat)

Chronic: glycogenosis, mucopolysaccharidosis, Gaucher disease, Niemann-Pick disease, gangliodidiasis, Wolman 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: hepatoblastoma, hematoma, hemangioendothelioma

Metastatic: neuroblastoma, Wilms tumor, gonadal tumors.

Table 5.

Diseases that cause liver failure

NEWBORN AND INFANTS

Infections:

herpes viruses,

adenoviruses,

Metabolic disorders: hereditary fructose intolerance,

mitochondrial diseases,

tyrosinemia,

galactosemia,

neonatal iron storage disease.

myocarditis,

severe hypotension.

Drugs/toxins: valproate,

acetaminophen

CHILDREN AND TEENS

Infections:

herpes viruses,

adenoviruses,

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

BABIES

Microcephaly:

congenital cytomegalovirus,

rubella,

toxoplasmosis

Characteristic face type:

arteriohepatic dysplasia (Allagile syndrome)

Cataract:

galactosemia

Retinal pigmentation: Allagille syndrome

Abnormal findings on pulmonary ascultation: cystic fibrosis.

Neuromuscular disorders (tremor, lethargy): lipid storage disease, Wilson's disease, oxidative phosphorylation disorders

Prurith:

chronic cholestasis

Hemangiomas:

hemangiomatosis of the liver

Kayser-Fleischer rings:

Wilson's disease

Glossitis:

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 in 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 insult with dilatation of the Glisson capsule due to edema, which is responsible for the perceived pain localized to the liver.

Severe hepatosplenomegaly indicates a storage disease or malignant disease, although particularly striking hepatomegaly itself is associated with significant hepatic fibrosis

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

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

Ascites suggests increased portal venous pressure and deterioration of hepatic function.

Certain physical signs raise significant suspicion for specific liver disease. In neonates 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 typically present with a characteristic facial pattern (beaked nose, high forehead, butterfly-shaped vertebrae, and a murmur on cardiovascular auscultation due to peripheral pulmonary stenosis and posterior embryotoxin on ophthalmologic examination.

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 damage to 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.

Table 7.

Objectives of the stepwise assessment of infants with jaundice

Recognize cholestasis (unconjugated or physiological hyperbilirubinemia)

Separate specific disease 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.

Stepwise assessment of infants with suspected cholestatic liver disease

Confirm cholestasis

Clinical assessment (family history, feeding history, physical examination)

Fractionation of serum bilirubin and determination of serum bile acid levels

Stool color assessment

Hepatic synthetic function index (prothrombin and albumin time)

Recognize specific disease entities

Viral and bacterial cultures (blood, urine, cerebrospinal fluid)

Hepatitis B surface antigen and other viral and syphilis titers (VDRL) in selected patients at risk

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 levels

Liver biopsy

Liver function tests

However, the term LFT is not entirely accurate because only two of the parameters commonly obtained are true measures of liver function—prothrombin time (PT) and serum albumin levels—both of which assess synthetic capacity. All of the other parameters are essentially indirect indicators of liver function, and many of these indicators are altered in situations other than liver disease. For example, elevated aspartate aminotransferase (AST) is associated with red blood cell hemolysis, muscle breakdown, and pancreatic disease.

Of all the laboratory tests performed, bilirubin fractionation is the most important.

The healthy mature liver removes unconjugated bilirubin from the blood and mediates the conjugation of unconjugated bilirubin with two glucuronic acid molecules. Bilirubin conjugation converts an essentially fat-soluble substance (unconjugated bilirubin) into a water-soluble substance (conjugated bilirubin) that can be excreted 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.

Physiological neonatal jaundice (in which unconjugated bilirubin levels increase) results from immaturity of the glucuronyl transferase system responsible for bilirubin conjugation. Breastfeeding-associated jaundice (a slight temporary decrease in conjugating capacity) is usually the result of components contained in breast milk.

If conjugated (direct, bound) bilirubin is present, evaluation must be aggressive. A serum conjugated bilirubin value greater than 17 mcmol/L (1 mg/dL) or greater than 15% of total bilirubin should be considered abnormal and promptly evaluated! Unconjugated bilirubin levels reflect excess bilirubin production (eg, as a result of hemolysis) or a decreased ability of the liver to bind bilirubin. The conjugated fraction is associated with severe 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 urobilinogen is excreted in the stool as coprobilinogen; 20% undergoes enterohepatic recirculation. Only a small fraction ends up in the urine, but it increases in the presence of hepatocellular damage due to decreased hepatic 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 into urobilinogen. Interestingly, delta-bilirubin, due to its covalent binding to albumin, is not excreted in urine, and therefore tends to remain elevated in the serum for some time after the initial cholestatic insult, 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 tests of hepatocyte necrolysis. Significant increases in these enzymes, which are released from damaged hepatocytes, indicate hepatocellular damage. Slightly abnormal levels may also be associated with cholestatic processes, since reverse flow 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 to the alpha-keto group of ketoglutaric acid, which leads to the formation of pyruvic acid (ALT) and oxaloacetic acid (AST).

Alkaline phosphatase (AP) levels

AP is located primarily in the canalicular membrane of liver cells, therefore, elevated serum AP levels usually indicate 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 typically found in children during periods of accelerated growth, such as the pubertal growth spurt. Particularly high levels should lead to suspicion of possible bone pathology (eg, rickets), especially if the 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 AR values 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 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 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. 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 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 normal cholic and chenodeoxycholic acids. The interpretation of elevated serum bile acid levels in neonates and infants is complicated by the presence of relative "physiologic 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 metabolite precursors makes possible definition specific congenital disorders of bile acid metabolism. With recent technological advances such as fast atom bombardment mass spectrometry, it is possible to rapidly analyze urine samples from individuals suspected of having specific bile acid disorders and to identify specific inborn errors of bile acid metabolism, such as 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.

Albumen

Decreased serum levels of albumin, which is synthesized in the rough endoplasmic reticulum of healthy hepatocytes, may suggest decreased production due to decreased liver function following hepatocellular disease. However, low albumin concentration is a late manifestation of liver disease. When present, it raises the suspicion of a chronic disease. Clearly, a sharp decrease in albumin in a patient with long-standing disease is particularly alarming, 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 colonic bacteria on proteins in the diet, and the liver plays a major role in its elimination. Of course, 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 quickly transported to the laboratory on ice - sharply elevated ammonia levels may be obtained).

Prothrombin time (PT)

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

Trace elements and vitamin-related disorders

Copper accumulates in the liver during cholestasis because it is excreted primarily through 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 pre-existing liver damage.

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

IMAGING AND HISTOPATHOLOGY OF THE LIVER AND BILIARY TRACT

Abdominal ultrasonography -

is relatively inexpensive, easy to perform, and can usually be attempted without sedating the patient. It allows you to measure liver size, confirm changes in liver structure and the presence of cystic or non-cystic parenchymal lesions. Common bile duct cysts and stones can be detected with 95% accuracy. Ultrasonography is also useful as a screening method for liver space-occupying lesions 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 radiolabeled N-substituted imino-diacetate (IDA) atoms labeled with technetium-99, such as diisopropyl-IDA (DISIDA) or para-isopropyl-IDA (PIPIDA), is used in the evaluation 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 tracer in the intestine may not represent an obstructive defect, but rather a parenchymal disease process in which the uptake or concentration of the tracer is poor. To ease bile flow, patients are often given phenobarbital (5 mg/kg per day, divided into 2 daily doses) for 3-5 days before undergoing the scan. Phenobarbital facilitates bile flow by inducing specific liver enzymes in infants with immature hepatic enzyme systems but no other abnormalities.

Computed tomography (CT) and magnetic resonance imaging (MRI)

These two methods are rarely necessary as first-line methods for diagnosing liver disease in children. However, they can be useful in specific situations. CT scanning of the liver can reveal deposits of glycogen, iron and lipids within the liver parenchyma and can clearly identify and characterize liver neoplasms. However, CT is more expensive and technically more difficult in infants than ultrasonography and exposes the patient to ionizing radiation. MRI has comparable sensitivity to CT in recognizing chemical differences in tissue and identifying 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 -

a 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 stay in the operating room or be 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 whether there is any storage disorder: confirm the presence of Wilson's disease (copper storage), glycogen storage disease or neonatal iron storage disease, as well as many other pathological conditions. Tissue histology 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, thereby eliminating the risk of subjecting a child with cholestasis caused by intrahepatic bile duct insufficiency to unnecessary surgery.

ABBREVIATIONS

AIH - autoimmune hepatitis

ALT - alanine aminotransferase

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 due to viral hepatitis acquired in utero or postnatally.

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

Biliary atresia

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

Because cirrhosis develops quickly, surgical correction of biliary atresia is most effective if performed before the age of 3 months, which emphasizes the need for rapid and accurate diagnosis of the cause of liver dysfunction observed in an infant. As with idiopathic neonatal hepatitis, children with biliary atresia are admitted with signs of cholestasis. Once these signs are recognized, abdominal ultrasonography can rule out the presence of a common bile duct cyst.

Other reasons

Other disease entities leading to liver dysfunction in the newborn and infant can be diagnosed through a combination of general examinations.

LIVER DISEASES IN AN OLDER CHILD

The main causes of liver disease observed after infancy are toxic, infectious, metabolic, autoimmune, vascular and infiltrative. The relative frequency of each disorder varies depending on the age of the patient. Viral hepatitis occurs in patients of all ages, as does liver disease caused by cardiac or collagen vascular disease. Disorders of fat metabolism are observed in older infancy and early childhood. Wilson's disease is usually detected in late childhood or adolescence.

Acute hepatitis

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

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 been rarely 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 common in the Mediterranean basin and is 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. Cases diagnosed in North America were in patients who brought the virus from abroad. It can be a particularly devastating disease 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 even within 6 months. The most acute hepatitis disappears in children within 3 months.

Autoimmune hepatitis (AIH)

AIH is an 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: AIH type I is more common in women and is characterized by positive antinuclear antibody, and AIH type II 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 elevated 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 values are usually normal or only slightly elevated. 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 (without evidence of underlying disease and unknown etiology) and is usually associated with inflammatory bowel disease. Secondary sclerosing cholangitis occurs as a result of stones, postoperative strictures, or tumors.

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.

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

Ischemic hepatitis occurs as a result of congestive heart failure, shock (eg, dehydration), asphyxia, cardiac and respiratory arrest, or seizures. Aminotransferases are usually 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 being affected as an “innocent bystander” to the initial process.

Infiltrative liver disorders are observed in leukemia, lymphoma and neuroblastoma, but these nosological entities are usually quickly identified. Similarly, primary liver tumors are easily identified in a child who presents with hepatomegaly or abdominal distension. Less commonly, children initially present with jaundice and weight loss.

CONCLUSION

An advancement is the availability of numerous treatment options for liver disease other than transplantation (Table 9).

Table 9

Options for children with liver disease beyond transplantation

Replacement of the deficient abnormal end product, such as oral administration of primary (essential?) bile acids (in patients with disorders of bile acid biosynthesis)

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