Extragenital pathology in obstetrics: Cholestatic hepatosis of pregnant women. Hepatosis during pregnancy: symptoms and treatment, effect on the fetus Cholestasis in pregnant women, ICD 10 code

The pregnancy period is marked for a woman not only by the joy of bearing a child, but also by the risk of various diseases. Organ systems cannot cope with their functions due to the increasing weight of the expectant mother and the constant consumption of nutrients by the fetus. The most significant problems arise with the liver, and one of the most common among them is hepatosis. This article will discuss the causes of this disease, its symptoms, principles of treatment, diagnosis and the basics of prevention.

What kind of disease is this

Hepatosis is the accumulation of fatty inclusions in hepatocytes - liver cells and, in the absence of timely treatment, is accompanied by degradation of hepatocytes. In this case, inflammatory processes do not occur. There are several types of this pathology, such as fatty and cholestatic. Each species has its own code in the International Classification of Diseases. The code for hepatosis according to ICD 10 is K70.

What are the dangers during pregnancy: consequences for the child

The impact of this disease on both the expectant mother and the developing fetus cannot be underestimated. Most often, hepatosis leads to the following complications:

• oxygen and placental starvation of the fetus, accompanied by delays in its development;
• birth strangulation of an infant, pulmonary failure in the postpartum period;
• stimulation of premature labor, most often at the beginning of the third trimester and, as a result, prematurity of the baby;
• the appearance of hematomas and vascular networks on the skin of the fetus;
• intrauterine death. Most typical for the fatty form of the disease.

Important! In the acute form of fatty hepatosis, natural childbirth is fraught with intense bleeding. Even if your condition has been stabilized and the pregnancy has been completed until the end of the ninth month, agree to a cesarean section to avoid possible complications.

Reasons for development

The main cause of hepatosis is pregnancy itself, or rather the processes that accompany it:

• changes in hormonal levels. An increase in the concentration of estrogen in the blood provokes rapid weight gain, thickening of bile and deterioration of the patency of the biliary tract;
• increase in fetal weight. The amniotic sac with water puts pressure on the liver, it is partially deformed, the outflow of bile worsens and the rate of cell recovery decreases;
• chronic liver or kidney diseases, in particular - liver failure;
• inflammatory processes in the abdominal cavity. Occur due to injuries or poorly performed surgical interventions;
• haemorrhoids. Since this pathology is accompanied by a decrease in the tone of the intestinal blood vessels, the blood supply to the liver also deteriorates;
• genetic predisposition. Hepatosis often occurs in women whose close relatives suffer from this disease;
• wrong diet. An abundance of fatty, fried foods, meat dishes and animal fats is bad for the health of liver cells;
• hypervitaminosis. Many women during pregnancy begin to take uncontrolled vitamin complexes, thereby disrupting the functioning of the liver.

Symptoms

Different types of this pathology are characterized by different symptoms.

Cholestatic

This form of hepatosis is characterized by the entry of a large amount of bile into the bloodstream. Her symptoms:

• intense itching. The bile pigment bilirubin irritates nerve receptors, resulting in an itchy sensation. It tends to get worse at night. In some pregnant women, scratching of the skin becomes uncontrollable, and they scratch themselves until they bleed;
• jaundice. Appears three to four weeks after itching occurs. Occurs on average in 20% of pregnant women. Characterized by yellowing of the whites of the eyes and skin;
• dry facial skin, the appearance of acne and fine wrinkles;
• weakness, sleep disturbance, apathy, which is accompanied by loss of appetite and nausea;
• light stool. The color is disturbed due to insufficient flow of bile into the digestive tract;
• dark color of urine. Occurs due to the disposal of excess bile pigment through the urinary system;
• change in blood composition. Determined using a general analysis, it shows an increase in the amount of bilirubin, cholesterol, and cholestasis.

Did you know? The liver has a unique ability to regenerate. If a person decides to become a donor and donate 75% of this organ to someone, then the liver restores its natural size within two weeks after the operation! The rate of regeneration is amazing, considering that it is the heaviest internal organ. On average, its weight is 1.2 kg- a large Chihuahua weighs exactly the same.

Fatty liver hepatosis

It occurs in four stages and is practically asymptomatic; if left untreated, it transforms into cirrhosis. Stage zero is not expressed; it is treated by changing lifestyle. Symptoms:

• heaviness in the area of ​​the right hypochondrium, radiating to the lower back, shoulder, shoulder blade and left half of the body;
• bitter taste on the root of the tongue, yellow coating on the tongue and tonsils;
• intestinal disorders, such as excessive gas formation, disorders, nausea;
• enlarged liver with protrusion from the hypochondrium, swelling of adjacent soft tissues;
• growth of adipose tissue on the internal organs of the abdominal cavity.

Diagnostics

It is extremely difficult to determine this disease during pregnancy due to the enlarged uterus and the inability to carry out procedures such as palpation and elastometry. Most often, diagnosis is based on the results of a general blood test and the patient’s complaints. Sometimes an ultrasound of the liver, a general urinalysis and an examination of the condition of the fundus are additionally prescribed. The cholestatic form is easier to diagnose than the fatty form.

Treatment

During pregnancy, treatment is carried out by adjusting the diet, herbal preparations, and less often - pharmaceutical medications.

Medicines

Treatment is carried out in three directions - the symptoms are eliminated, the placental blood supply to the fetus is stimulated, and abortion is prevented.

At an early stage of the disease, sorbents, antioxidants, hepatoprotectors, drugs with a choleretic effect and drugs to reduce the acidity of gastric juice are prescribed.
If hepatosis has developed into a more severe form, additional detoxification of the body is carried out, folic acid, antipruritic drugs and Cholestyramine are prescribed. In extreme cases, the patient is prescribed plasmapheresis - hardware blood purification.

Important! Aching pain in the right hypochondrium can be a sign not only of hepatosis, but also of a malfunction of the gallbladder, such as cholecystitis. Duodenal intubation is the only possible way to distinguish one disease from another; it is rarely performed due to the possible stimulation of premature labor.

Includes herbal decoctions with choleretic, antioxidant and restorative effects. Herbal infusions are used to make decoctions, so before purchasing the infusion, check the composition for the presence of strong allergens. If you plan to prepare the collection yourself, then use the following recipe.
Ingredients:

• licorice - 20 g;
• string leaves - 15 g;
• birch leaves - 15 g;
• sage leaves - 10 g;
• wormwood - 10 g;
• chamomile - 5 g;
• linden - 5 g;
• calamus root - 5 g.

Cooking method:

1. Mix and grind all the ingredients of the collection.
2. In an enamel saucepan, bring 1 liter of water to a boil.
3. Add 15 g of the collection to the saucepan. Cover the lid with the saucepan and simmer the collection over low heat for twenty minutes.
4. Remove the saucepan from the heat, wrap it in a blanket and leave to steep for an hour and a half.
5. Strain the finished broth through a gauze cloth and pour into a ceramic container. Take a decoction of 50 ml twice a day for three weeks, then take a break for a week and repeat the course if necessary.

Did you know? At the eighth week of intrauterine development, the liver makes up 50–60% of the fetal body weight. Over the entire period from its formation to the birth of the baby, it pumps more than 20,000 liters of blood through itself. If this organ did not exist, the baby would receive poisoning from every product his mother drank and ate.. It is not for nothing that the Lezgins and some African peoples believe that the human soul is contained in the liver, and they never eat animal livers.

Another collection with pronounced cleansing properties is prepared as follows.

Ingredients:

• licorice root - 20 g;
• birch leaves - 20 g;
• rose hips - 15 g;
• hawthorn - 15 g;
• rowan - 15 g;
• lingonberries - 10 g;
• nettle leaves - 10 g;
• marshmallow root - 10 g;
• St. John's wort - 5 g.

Cooking method:

1. Mix and grind all ingredients. Boil 1.5 liters of water, add 30 g of the mixture to the boiling water.
2. Cover the container with water with a lid and place it in a warm place for two hours.
3. Strain the finished infusion through a strainer into a glass container and seal it tightly for the storage period.
4. Use the infusion twice a day, 100 ml, for two weeks or until symptoms are completely eliminated.

Diet

The therapeutic diet called table No. 5 provides for the complete exclusion of products containing animal fats, fatty meats, and fast food. To reduce the load on your liver, you should avoid:

• smoked meats;
• conservation;
• salty foods;
• and other store-bought sweets;
• alcoholic drinks;
• tea and tea drinks.

Eat as little as possible of foods that cause gas formation - white bread, legumes, baked goods, mushrooms.

Important! Hepatosis has a negative impact mainly on the baby. A young mother gets rid of this disease one to one and a half weeks after giving birth, and the child can suffer from its consequences for many years. To prevent this from happening, be attentive to yourself and seek medical help at the first deviation from normal health.

The diet can include:

Prevention measures

To prevent the development of this disease, follow these recommendations:

• First of all, control your diet. Eat foods rich in fiber and low in fat. Don’t get carried away with sweets, preserves, and smoked foods;
• lead an active lifestyle. Sign up for a swimming pool or yoga for pregnant women, and attend classes regularly. If this is not possible, walk outdoors more often;
• get rid of bad habits. Stick to your daily routine so that the body can prepare for sleep and produce enzymes to digest food at the right time;
• avoid stressful situations, conflict as little as possible. If you have anxious thoughts about the upcoming birth, talk to someone close to you or make an appointment with a psychologist.

Hepatosis in any of its forms begins to develop in pregnant women in the third trimester of pregnancy. This pathology affects liver cells and interferes with the normal functioning of the organ. There are symptoms characteristic of each type of disease.

Did you know? The world's first liver transplant operation was performed in the 1960s at the American University in Colorado. The operation was successful and the patient began to recover. Unfortunately, medicine at that time was not yet sufficiently developed. Due to incorrectly prescribed immunosuppressive drugs, which were supposed to protect the transplanted organ from rejection, the patient died several weeks after the operation. Nowadays, more than 8 thousand such operations are performed annually.

Timely diagnosis and competent medical intervention will help stop the progression of the disease and reduce its impact on the baby. If your liver is functioning normally, support its functioning with proper nutrition and moderate exercise - this way you will avoid the occurrence of hepatosis.

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Cholestasis is a violation of the flow or formation of bile due to a pathological process localized in any area from the sinusoidal membrane of the hepatocyte to the papilla of Vater.

ICD-10 K71.0

general information

In this case, there is a decrease in hepatic excretion of water, bilirubin, bile acids and accumulation of bile in hepatocytes and bile ducts; retention and accumulation in the blood of components excreted into bile. The terms “cholestasis” and “obstructive jaundice” are not synonymous: in many cases of cholestasis, there is no mechanical blockage of the bile ducts.

Clinical picture

The disease is characterized by: skin itching (not always); steatorrhea and diarrhea (due to a decrease in the level of bile acids in the intestines and impaired digestion of fats), night blindness, osteomalacia, osteoporosis and bone fractures, petechiae, spontaneous hemorrhages, increased thrombin time, muscle weakness (impaired absorption of fat-soluble vitamins A, D, K , E), skin xanthomas and xanthelasmas, increased blood levels of bilirubin, alkaline phosphatase, more than 3 times higher than normal, GGTP, total cholesterol, phospholipids, LDL, TG; in urine - conjugated bilirubin, urobilinogen.
Long-term cholestasis leads to the formation of primary biliary cirrhosis.

Diagnostics

Questioning - an indication in the anamnesis of signs of diseases that can cause cholestasis (cholelithiasis, tumor formations, inflammation of the biliary system, taking medications).
examination - petechial rashes of xanthoma and xanthelase; yellowness of the skin is possible.
Laboratory research
Required:
complete blood count - the appearance of target-shaped red blood cells, an increase in the surface area of ​​red blood cells; anemia, neutrophilic leukocytosis;
general urine test - conjugated bilirubin, urobilinogen;
blood bilirubin – increased;
blood enzymes – AST, ALAT, GGTP, alkaline phosphatase;
general cholesterol and its fractions;
TG;
blood albumins and globulins;
prothrombin time.
If indicated:
bacteriological examination of blood culture (if there is a suspicion of sepsis);
coagulogram;
markers of hepatitis A, B, C, D viruses.
Instrumental research methods
Required:
Ultrasound of the abdominal organs (determining the condition of the bile ducts, the size and condition of the parenchyma of the liver and spleen; size, shape, wall thickness; the presence of stones in the gallbladder and bile ducts).
If indicated:
ERCP (CHCHG);
targeted percutaneous puncture biopsy of the liver (determination of the morphological substrate of the disease).
Specialist consultations
Required:
Not shown.
If indicated:
infectious disease specialist - if markers of the hepatitis virus are detected;
surgeon - for extrahepatic cholestasis;
oncologist.

Treatment

Pharmacotherapy
Standard:
As an addition to the treatment of the underlying disease that caused the development of cholestasis:
cholestyramine – 4 g 2-3 times a day;
urosodeoxycholic acid – 13-15 mg/kg per day;
ondasetron – 1 tablet. 2 times or parenterally 1 ml (reduce itching).
If indicated:
ademetionine – IM or IV 400-800 mg/day;
fat-soluble vitamins (orally): vitamin K – 10 mg/day; A – 25,000 IU/day; D 400-4000 IU/day;
calcium in the form of skim milk or dietary supplements.
Surgery
For bile duct obstruction – endoscopic sphincterotomy, nasobiliary drainage, stenting, surgical treatment.

When classifying liver diseases in this group of patients, pregnancy is considered as a possible “etiological” factor (Table 21.2).

Table 21.2. Classification of liver diseases in pregnant women

Liver diseases caused by pregnancy. Liver damage due to hyperemesis gravidarum. Uncontrollable vomiting of pregnant women develops in the first trimester and can lead to dehydration, electrolyte imbalance, and nutritional deficiency. Development frequency - 0.02 - 0.6%. Risk factors: age under 25 years, excess weight, multiple pregnancy.

Liver dysfunction occurs in 50% of patients 1-3 weeks after the onset of severe vomiting and is characterized by jaundice, dark urine and, sometimes, itching. A biochemical study reveals a moderate increase in bilirubin, transaminases - alanine (ALT) and aspartic (AST) and alkaline phosphatase (ALP).

Symptomatic treatment is carried out: rehydration, antiemetic drugs. After correction of fluid and electrolyte disturbances and return to a normal diet, liver function tests (LFTs) return to normal within a few days. Differential diagnosis is carried out with viral and drug-induced hepatitis. The prognosis is favorable, although similar changes may develop in subsequent pregnancies.

Intrahepatic cholestasis of pregnancy (ICP). Also referred to as pruritus, cholestatic jaundice, cholestasis of pregnancy. ICP is a relatively benign cholestatic disease that usually develops in the third trimester, resolves spontaneously a few days after birth, and often recurs in subsequent pregnancies.

In Western Europe and Canada, ICP occurs in 0.1-0.2% of pregnant women. The highest frequency is described in the Scandinavian countries and Chile: 1-3% and 4.7-6.1%, respectively. The disease most often develops in women with a family history of ICP or with indications of the development of intrahepatic cholestasis when taking oral contraceptives.

The etiology and pathogenesis have not been sufficiently studied. In the development of ICP, the leading role is given to congenital hypersensitivity to the cholestatic effects of estrogens.

The disease usually begins at 28-30 weeks. pregnancy (less often - earlier) with the appearance of skin itching, which is characterized by variability, often intensifies at night, and affects the torso, limbs, including palms and feet. A few weeks after the onset of itching, jaundice appears in 20-25% of patients, which is accompanied by darkening of the urine and lightening of the stool. At the same time, good health is maintained, in contrast to acute viral hepatitis (AVH). Nausea, vomiting, anorexia, and abdominal pain occur rarely. The size of the liver and spleen does not change. In blood tests, the concentration of bile acids is significantly increased, which may be the first and only change.

The level of bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase (GGTP), 5"-nucleotidase, cholesterol and triglycerides increases. Transaminases increase moderately.

To diagnose ICP, a liver biopsy is rarely necessary. Morphologically, ICP is characterized by centrilobular cholestasis and bile plugs in small bile canaliculi, which may be dilated. Hepatocellular necrosis and signs of inflammation are usually absent. After birth, the histological picture returns to normal.

The diagnosis is made on the basis of clinical and biochemical data. Most often, ICP is differentiated from choledocholithiasis, which is characterized by abdominal pain and fever. In this case, ultrasound examination (ultrasound) helps in diagnosis.

ICP is relatively harmless to mother and baby. Premature delivery is rarely necessary.

Treatment is symptomatic and aimed at ensuring maximum comfort for mother and child. Cholestyramine is used as the drug of choice to reduce skin itching in a daily dose of 10-12 g, divided into 3-4 doses. The drug is not toxic, however, its effectiveness is low. In patients with severe symptoms of night itching, sleeping pills may be used. There is some data on the use of ursodeoxycholic acid () in the treatment of ICP. Uncontrolled studies have shown a reduction in itching and improvement in laboratory parameters with a short course of UDCA at a dose of 1 g. per day, divided into three doses. A positive effect on skin itching was noted when a 7-day course of dexamethasone was prescribed at a daily dose of 12 mg. Some studies have shown the beneficial effects of S-adenosine-L-methionine.

Women with ICP have an increased risk of postpartum hemorrhage due to reduced absorption of vitamin K, so it is recommended to include vitamin K injections in treatment.

The prognosis for the mother is characterized by an increased incidence of postpartum hemorrhage and urinary tract infections. Repeated pregnancies increase the risk of gallstones. The baby has an increased risk of prematurity and low birth weight. Increased perinatal mortality.

Acute fatty liver of pregnancy (AFLP). It is a rare idiopathic liver disease that develops in the third trimester of pregnancy and has an extremely unfavorable prognosis. Liver biopsy reveals characteristic changes - microvesicular obesity of hepatocytes. A similar picture is observed with Reye's syndrome, genetic defects in the oxidation of long- and medium-chain fatty acids (deficiency of the corresponding acyl-CoA dehydrogenases), as well as when taking certain medications (tetracycline, valproic acid). In addition to the characteristic histological picture, these conditions, which belong to the group of mitochondrial cytopathies, have similar clinical and laboratory findings.

The incidence of CVD is 1 in 13,000 births. The risk of development is increased in primiparous women, in multiple pregnancies, if the fetus is a boy.

The exact cause of AFB has not been established. It is hypothesized that there is a genetic deficiency of 3-hydroxy-acyl-CoA dehydrogenase, which is involved in the oxidation of long-chain fatty acids. AFB develops in mothers who are heterozygous carriers of the gene encoding this enzyme, if the fetus is homozygous for this trait.

AFB usually develops no earlier than 26 weeks. pregnancy (described in other stages of pregnancy and in the immediate postpartum period). The onset is nonspecific with the appearance of weakness, nausea, vomiting, headache, pain in the right hypochondrium or epigastric region, which can simulate reflux esophagitis. In 1-2 weeks. from the occurrence of these symptoms, signs of liver failure appear - jaundice and hepatic encephalopathy (HE). If AFLP is not recognized in a timely manner, it progresses with the development of fulminant liver failure (FLF), coagulopathy, renal failure, and can lead to death.

Physical examination reveals minor changes: abdominal pain in the right hypochondrium (a common but not specific symptom), the liver is reduced in size and cannot be palpated, and in the later stages of the disease jaundice, ascites, edema, and signs of PE occur.

Blood tests reveal red blood cells containing nuclei and segmented red blood cells, pronounced leukocytosis (15x10 9 l or more), signs of disseminated intravascular coagulation syndrome (DIC syndrome) - an increase in prothrombin (PT) and partial thromboplastin time (PTT), an increase in the content of degradation products fibrinogen, decrease in fibrinogen and platelets. Changes in PFT concern an increase in bilirubin, aminotransferase activity and alkaline phosphatase. Hypoglycemia, hyponatremia are also determined, and the concentration of creatinine and uric acid increases. Ultrasound and computed tomography (CT) of the liver may reveal signs of fatty degeneration, but their absence does not exclude the diagnosis of AFLP.

Liver biopsy gives a characteristic picture: microvesicular obesity of centrilobular hepatocytes. Traditional histological examination may not confirm the diagnosis due to the fact that the fat moves during the fixation process. To avoid false negative results, frozen liver tissue samples should be tested.

The diagnosis of acute liver disease is made based on a combination of clinical and laboratory data with signs of microvesicular fatty liver. Differential diagnosis is made with OVH, liver damage in preeclampsia/eclampsia, drug-induced hepatitis (tetracycline, valproic acid). OVH develops at any stage of pregnancy, has an epidemiological history and a characteristic serological profile. In case of acute hepatitis, transaminase levels are usually higher than in case of acute bile duct disease, and disseminated intravascular coagulation syndrome is not typical.

Preeclampsia/eclampsia develops in 20-40% of patients with AFB, which causes significant difficulties in the differential diagnosis of these conditions. In this case, a liver biopsy is not required, since the treatment measures are similar.

No specific therapy has been developed for acute pancreatitis. The treatment of choice remains immediate delivery (preferably via cesarean section) as soon as the diagnosis is established, and supportive care. Before and after birth, platelet levels, PT, PTT, and glycemia are monitored. If necessary, these indicators are corrected: glucose solution, fresh frozen plasma, and platelet mass are administered intravenously. If conservative measures are ineffective and FPN progresses, the issue of liver transplantation is decided.

The prognosis for the mother and fetus is unfavorable: maternal mortality - 50% (with immediate delivery - 15%), infant mortality - 50% (with immediate delivery - 36%). In women who survive AFLP, liver function quickly improves after childbirth and there are no further signs of liver disease. If a subsequent pregnancy develops, it usually proceeds without complications, although repeated episodes of AFLP have been described.

Liver damage in preeclampsia/eclampsia. Preeclampsia is a systemic disease of unknown etiology, which usually develops in the second trimester of pregnancy and is characterized by a triad of symptoms: arterial hypertension, proteinuria, edema. Eclampsia is a more advanced stage of the disease with the appearance of seizures and/or coma. Associated with renal failure, coagulopathy, microangiopathic hemolytic anemia, ischemic necrosis of many organs. Liver damage in preeclampsia and eclampsia is similar and ranges from mild hepatocellular necrosis to liver rupture.

Preeclampsia develops in 5-10%, eclampsia in 0.1-0.2% of pregnant women in the second trimester. May develop after childbirth. Risk factors are: upper and lower limits of age favorable for pregnancy, first pregnancy, multiple pregnancy, polyhydramnios, family history of preeclampsia, pre-existing diseases: diabetes mellitus, arterial hypertension.

The etiology and pathogenesis of preeclampsia/eclampsia are not fully understood. The currently proposed hypothesis involves vasospasm and increased endothelial reactivity, leading to hypertension, increased coagulation, and intravascular fibrin deposition. The impact of reduced nitric oxide synthesis is discussed.

With moderate preeclampsia, blood pressure is increased from 140/90 mmHg. up to 160/110 mmHg In severe preeclampsia, blood pressure exceeds 160/110 mmHg. In severe cases, pain in the epigastrium and right hypochondrium, headaches, impaired visual fields, oliguria, and heart failure may appear. The size of the liver remains within normal limits or there is a slight increase. Blood tests show a significant increase in transaminases, which is proportional to the severity of the disease, the level of uric acid and bilirubin increases, thrombocytopenia, disseminated intravascular coagulation syndrome, and microangiopathic hemolytic anemia develop. Complications of preeclampsia/eclampsia include HELLP syndrome and liver rupture.

A histological examination of liver tissue reveals diffuse fibrin deposition around the sinusoids (fibrin is partially deposited in the small vessels of the liver), hemorrhages, and necrosis of hepatocytes.

The diagnosis is made based on clinical and laboratory data. Differential diagnosis is carried out with AFPP.

The choice of treatment method depends on the severity of the disease and the timing of pregnancy. For moderate eclampsia and gestational age less than 36 weeks. maintenance therapy is carried out. Hypertension is controlled with hydralazine or labetalol. Magnesium sulfate is used to prevent and control seizures. Low-dose aspirin can be used to prevent the progression of preeclampsia. The only effective treatment for severe preeclampsia and eclampsia is immediate delivery. After birth, laboratory changes and the histological picture of the liver return to normal.

The outcome depends on the severity of preeclampsia/eclampsia, the age of the mother (premature for pregnancy), pre-existing diseases in the mother (diabetes mellitus, arterial hypertension).

The prognosis for the mother is associated with an increase in mortality (in specialized centers about 1%), most of which - 80% - is due to complications from the central nervous system; with an increased risk of liver rupture and premature placental abruption. The risk of developing preeclampsia/eclampsia in the next pregnancy is 20-43%. Babies born to mothers with preeclampsia/eclampsia have low birth weight and developmental delays.

HELLP syndrome. It was first designated in 1982. in USA. Characterized by microangiopathic hemolytic anemia ( H emolisis), increased activity of liver enzymes ( E levated L iver enzymes) and thrombocytopenia ( L ow P latelet count).

HELLP syndrome is registered in 0.2-0.6% of pregnant women. Occurs in 4-12% of patients with severe preeclampsia. Most often develops after 32 weeks. pregnancy. Appears in 30% of women after childbirth. The risk of HELLP syndrome is increased in multiparous women over the age of 25 years.

The reasons for the development of the syndrome have not been fully elucidated. Factors such as vasospasm and hypercoagulation may be involved in its development.

Patients with HELLP syndrome have nonspecific symptoms: pain in the epigastric region or in the right hypochondrium, nausea, vomiting, weakness, headaches. The majority have moderate arterial hypertension.

There are no specific symptoms on physical examination. Blood tests: microangiopathic hemolytic anemia with increased levels of lactate dehydrogenase, indirect hyperbilirubinemia, increased transaminase activity, severe thrombocytopenia, decreased haptoglobin levels, a slight increase in PT (respectively decreased PI) and PTT, increased levels of uric acid and creatinine. Urine tests show proteinuria.

The diagnosis is made based on a combination of three laboratory signs. Differential diagnosis is carried out with severe preeclampsia, acute bile duct disease.

The treatment plan includes monitoring of blood pressure, platelet count, and coagulation tests. If the fetal lungs are mature, or there are signs of significant deterioration in the condition of the mother or fetus, then immediate delivery is performed. If the gestational age is less than 35 weeks and the mother's condition is stable, then corticosteroids are administered for several days, after which delivery occurs. If necessary, transfusion of fresh frozen plasma and platelets is carried out.

Prognosis for the mother: increased risk of disseminated intravascular coagulation syndrome, liver failure, cardiopulmonary failure, premature placental rejection. Repeated episodes develop in 4-22% of patients.

Prognosis for the fetus: increased mortality to 10-60%, increased risk of premature birth, developmental delay, risk of DIC and thrombocytopenia.

Acute liver rupture. It is a rare complication of pregnancy. More than 90% of cases are associated with preeclampsia and eclampsia. It can also develop, but much less frequently, with hepatocellular carcinoma, adenoma, hemangiomas, liver abscess, acute liver disease, HELLP syndrome.

The incidence ranges from 1 to 77 cases per 100,000 pregnant women. Develops in 1-2% of patients with preeclampsia/eclampsia, usually in the third trimester. Up to 25% of cases occur within 48 hours after birth. More often observed in multiparous women over 30 years of age.

The etiology has not been definitively established. Hemorrhage and liver rupture are likely due to severe hepatocyte necrosis and coagulopathy in severe preeclampsia/eclampsia.

The disease begins acutely with the appearance of sharp pain in the right hypochondrium, which can radiate to the neck and shoulder blade. Up to 75% of cases are associated with rupture of the right lobe of the liver. If a rupture of the left lobe occurs, the pain is usually localized in the epigastric region. Nausea and vomiting may also occur.

On physical examination, signs of preeclampsia and abdominal muscle tension are observed. Within a few hours of the onset of pain, hypovolemic shock develops in the absence of signs of external bleeding. Blood tests show anemia and a decrease in hematocrit, and a significant increase in transaminases. The remaining changes correspond to those in preeclampsia.

The diagnosis is made based on clinical data (pain in the right hypochondrium and hypovolemic shock) and detection of hemorrhage and liver rupture according to ultrasound and CT. Diagnostic laparotomy, peritoneal lavage, and angiography may also be used for diagnosis.

Differential diagnosis is carried out with other conditions that can give similar symptoms: placental rejection, perforation of a hollow organ, uterine rupture, torsion of the uterus or ovary, rupture of a splenic artery aneurysm.

Early recognition of acute liver rupture is a necessary condition for successful treatment. Stabilization of hemodynamic parameters and immediate delivery are necessary. Transfusions of blood products are carried out. Surgical treatment includes: evacuation of hemorrhagic fluid, local administration of hemostatic agents, wound suturing, ligation of the hepatic artery, partial hepatectomy, percutaneous catheter embolization of the hepatic artery. Postoperative complications include recurrent bleeding and abscess formation.

There was an increase in maternal mortality to 49% and child mortality to 59%. In patients who survive acute liver rupture, the hematoma gradually resolves over 6 months. Repeated episodes have been described in isolated cases.

Liver diseases that have peculiarities in pregnant women. Gallstone disease (GSD). The incidence of cholelithiasis in women is significantly higher than in men. It also depends on age: 2.5% of women aged 20-29 years and 25% aged 60-64 years suffer from cholelithiasis. The risk of cholelithiasis increases 3.3 times after the fourth pregnancy.

During pregnancy, cholesterol is concentrated in the liver and gallbladder bile. The total content of bile acids increases, but at the same time the sequestration of bile acids in the gallbladder and small intestine increases, due to reduced motility. This leads to a decrease in the secretion of bile acids into bile, a decrease in the enterohepatic circulation of bile acids, and a decrease in the ratio of chenodeoxycholic to cholic acid. These changes predispose to the precipitation of cholesterol in the bile. During pregnancy, the residual volume and fasting volume of the gallbladder also increases due to a decrease in its contractility.

Biliary sludge develops in 30% of women at the end of the third trimester. In 10-12%, ultrasound reveals gallstones, and 30% of them develop attacks of biliary colic. Clinical and laboratory data are consistent with those of non-pregnant patients.

In most cases, conservative measures are effective. If choledocholithiasis develops, papillosphincterotomy may be performed. A safe method for dissolving sludge and cholesterol gallstones is the use of ursodeoxycholic acid (): this method is effective if the cholesterol nature of the stones is confirmed, if their size does not exceed 10 mm, and the volume of the bladder is filled no more than 1/3 while its function is preserved. Cholecystectomy is safest in the first and second trimesters. Laparoscopic cholecystectomy has an advantage over traditional cholecystectomy. After childbirth, biliary sludge disappears in 61% within 3 months and 96% within 12 months, small stones dissolve spontaneously in 30% of women within a year. Pregnancy is a predisposing factor not only to the development of cholelithiasis, but also to the manifestation of clinical symptoms in women who previously had “silent” stones.

Acute calculous cholecystitis. The frequency is 8 cases per 10,000 pregnant women. Therapy is usually conservative. It is often best to postpone surgery until after childbirth. In patients with recurrent symptoms or common bile duct obstruction, surgical intervention is necessary and is associated with a low risk of maternal and child mortality.

Hepatitis caused by infection with the herpes simplex virus (HSV). HSV hepatitis rarely develops in adults without signs of immunodeficiency. About half of these cases have been described in pregnant women. The mortality rate reaches 50%. The disease begins with fever, lasting from 4 to 14 days, against which systemic symptoms of a viral infection and abdominal pain appear, most often in the right hypochondrium. Complications from the upper respiratory tract develop and there are herpetic rashes on the cervix or external genitalia. There is usually no jaundice. The first symptom of the disease may be PE.

Blood tests are characterized by a dissociation between a sharp increase in transaminases (up to 1000-2000 IU) and a slight increase in bilirubin. PV increases. X-ray examination of the lungs may show signs of pneumonia.

A liver biopsy can help in diagnosis. Characteristic signs are: foci or confluent fields of hemorrhagic and coagu intranuclear herpetic inclusions in viable hepatocytes.

A study of HSV culture in liver tissue, in the mucous membrane of the cervical canal, in a pharyngeal smear, as well as serological studies is carried out.

Treatment is acyclovir or its analogues. Response to treatment is rapid and leads to a significant reduction in maternal mortality. If liver failure develops, supportive measures are taken.

Although vertical transmission of HSV is not common, infants born to mothers who have had HSV hepatitis should be screened for infection immediately after birth.

Budd-Chiari syndrome (see chapter 20). Represents occlusion of one or more hepatic veins. The most common form of vascular thrombosis described in pregnant women. A predisposing factor is considered to be an estrogen-mediated increase in blood coagulation associated with a decrease in antithrombin-III activity. In some women, hepatic vein thrombosis is associated with widespread venous thrombosis, which can develop simultaneously in the iliac vein or inferior vena cava. In most cases, it is registered within 2 months or immediately after birth. May develop after abortion.

The disease begins acutely with the appearance of abdominal pain, then develops hepatomegaly and ascites, resistant to diuretics. Splenomegaly occurs in 50% of patients. Blood tests show a moderate increase in bilirubin, transaminases, and alkaline phosphatase. When examining ascitic fluid: protein 1.5-3 g/dl, serum-ascitic albumin gradient > 1.1, leukocytes< 100/мм 3 .

Diagnosis and treatment measures correspond to those in non-pregnant patients.

The prognosis is unfavorable: mortality without liver transplantation is more than 70%.

Viral hepatitis E. An epidemic form of hepatitis, transmitted by the fecal-oral route, the frequency and severity of which increases in pregnant women. The mortality rate from HEV (hepatitis E virus) hepatitis in pregnant women is 15-20%, while in the population it is 2-5%. The risk of spontaneous abortion and intrauterine fetal death is about 12%. Pregnant women must be isolated from the source of infection. Specific treatment and prevention have not been developed.

Liver diseases not associated with pregnancy. Viral hepatitis (see also chapter 3.4). Characteristics of viral hepatitis in pregnant women are presented in Table. 21.3.

Pregnancy with chronic liver diseases . Pregnancy in chronic liver diseases occurs rarely due to the development of amenorrhea and infertility. However, in women with compensated liver disease, reproductive function is preserved and pregnancy may occur. Changes in liver function in such patients are unpredictable and pregnancy often proceeds without liver complications.

Autoimmune hepatitis. Most women receiving immunosuppressive therapy tolerate pregnancy well. However, a transient change in PFT is possible: an increase in bilirubin and alkaline phosphatase, which return to initial values ​​after childbirth. Cases of significant deterioration of the condition have been described, which requires an increase in the dose of corticosteroids. There have also been cases of death. However, no controlled studies have been conducted and it is not clear what caused the worsening of the condition. The prognosis for the fetus is worse than for the mother: the frequency of spontaneous abortions and intrauterine death increases.

Cirrhosis of the liver. Pregnancy in patients with cirrhosis is extremely rare. Assessing the actual risk of liver complications in such patients is difficult. In 30-40%, the level of bilirubin and alkaline phosphatase increases, which in 70% returns to initial values ​​after childbirth. Maternal mortality increases to 10.5%, 2/3 of which is caused by bleeding from esophageal varices (EVV), and 1/3 by liver failure. Overall mortality rates do not differ from those in nonpregnant women with cirrhosis.

Prevention of bleeding from varicose veins involves the application of a selective portacaval shunt or sclerotherapy. The number of spontaneous abortions increases significantly to 17%, premature births to 21%. Perinatal mortality reaches 20%. The risk of developing postpartum hemorrhage is 24%.

Table 21.3. Viral hepatitis in pregnant women

Sign	Spicy hepatitis A	Spicy Hepatitis B	Chronic hepatitis B	Acute or chronic hepatitis C	Spicy hepatitis E
Increased severity in pregnant women	No	No	Rarely	No	Yes
Risk factors for transmission to the child:
pregnancy period	III trimester, after childbirth	III trimester, after childbirth	Childbirth, after childbirth	Unknown	Unknown
maternal serology	HAV IgM	HBsAg Anti HBc IgM, HBeAg, HBV DNA	HBsAg anti HBc IgM HBeAg, HBV DNA	Anti HCV, HCV RNA	Anti HEV
hepatitis in a child	Rarely at 2-4 weeks	70% in the third trimester	80-90% if the mother has HBeAg; <25% если у матери HBeAb. Коррелирует с уровнем HBV DNA	Correlates with HCV RNA levels	Not described
Children acquiring carrier status	No	80-90%	80-90%	Less than 10%	Not described
Prevention in children	Specific immunoglobulin	Specific immunoglobulin, HBV vaccine		Not proven

Cholestatic hepatosis of pregnant women

Cholestatic hepatosis of pregnancy is also known as intrahepatic cholestasis of pregnancy, intrahepatic cholestatic jaundice of pregnancy, pre-benign jaundice of pregnancy, idiopathic jaundice of pregnancy, recurrent cholestatic intrahepatic jaundice.

ICD 10 code- K.83.1.

Epidemiology
Intrahepatic cholestasis of pregnancy is the second most common cause of jaundice in pregnant women after viral hepatitis. Etiologically it is associated only with pregnancy. According to WHO, this disease occurs in 0.1 - 2% of pregnant women.

Etiology and pathogenesis
The pathogenesis of intrahepatic cholestasis in pregnancy has not yet been precisely established. It is assumed that the excess of endogenous sex hormones, characteristic of the pregnancy period, has a stimulating effect on the processes of bile formation and an inhibitory effect on bile secretion.

Reduced bile secretion promotes reverse diffusion of bilirubin into the blood. This assumption is confirmed by the fact that this pathological syndrome develops in 80-90% of women in the second half of pregnancy and the rise in estrogen levels correlates with the development of skin itching. There has been a definite relationship between intrahepatic cholestasis of pregnancy and jaundice caused by hormonal contraceptives, although these diseases are not identical. A certain role in the development of intrahepatic cholestasis in pregnancy is assigned to genetic defects in the metabolism of sex hormones, which manifest themselves only during pregnancy.

Clinical picture
Intrahepatic cholestasis of pregnancy is characterized by painful skin itching and jaundice. Itchy skin sometimes occurs several weeks before the appearance of jaundice. Currently, some researchers consider itching of pregnancy to be the initial stage or an erased form of intrahepatic cholestasis of pregnancy. Pregnant women sometimes complain of nausea, vomiting, and slight pain in the upper abdomen, often in the right hypochondrium. Pain syndrome is not typical for this pathology; otherwise, the condition of pregnant women remains almost unchanged. The liver and spleen, as a rule, are not enlarged. The disease can occur at any stage of pregnancy, but is most often observed in the third trimester.

Laboratory diagnostics
Laboratory and biochemical studies, along with an increase in the level of bilirubin in the blood serum (mainly due to its direct fraction) and pronounced urobilinogenuria, reveal a significant increase (10-100 times) in the content of bile acids. An increase in their concentration often occurs due to cholic acid and less often chenodeoxycholic acid. With cholestasis of pregnancy, in addition to an increase in the content of bile acids, the activity of a number of excretory enzymes increases, indicating cholestasis (alkaline phosphatase, γ-glutamyl transpeptidase, 5-nucleotidase). The activity of transaminases (alanine aminotransferase and aspartate aminotransferase) remains within normal limits. In most pregnant women with cholestasis, the concentration of cholesterol, triglycerides, phospholipids, and β-lipoproteins increases. Very often their blood clotting indicators decrease - factors II, VII, IX, prothrombin. Sedimentary samples and proteinograms remain almost unchanged.

Histological studies of the liver in benign cholestasis of pregnancy show preservation of the structure of the lobules and portal fields, there are no signs of inflammation and necrosis. The only pathological sign is focal cholestasis with bile thrombi in dilated capillaries and deposition of bile pigment in adjacent liver cells. Intrahepatic cholestasis is more difficult to diagnose during the first pregnancy, but during a second pregnancy it is much easier, since the disease often recurs.

Differential diagnosis
Differential diagnosis of intrahepatic cholestasis in pregnant women should be carried out with acute and chronic hepatitis, drug-induced cholestasis, cholelithiasis with obstructive jaundice and primary biliary cirrhosis. For cholestasis in pregnancy, its pathognomonic onset is in the II-III trimesters of pregnancy, its recurrent nature in subsequent pregnancies, the absence of enlargement of the liver and spleen, normal levels of transaminase activity in most patients, the disappearance of all symptoms 1-2 weeks after birth. Acute viral hepatitis can develop throughout the entire period of pregnancy. It is characterized by an enlargement of the liver and very often the spleen, and a sharp increase in transaminase activity. Cholelithiasis and obstructive jaundice in pregnant women are recognized on the basis of known clinical signs, as well as ultrasound data of the biliary system.

In diagnostically difficult cases, a liver biopsy is indicated. This manipulation is no more risky during pregnancy than outside of it. However, it should be remembered that in pregnant women with intrahepatic cholestasis, the blood coagulation system often changes, so there is a high risk of bleeding.

Signs of cholestasis caused by the influence of pregnancy disappear 1-3 weeks after birth. Most authors believe that all manifestations of the disease disappear, as a rule, within 1-3 months after birth.

Course of pregnancy
The obstetric situation, as in all patients with liver pathology, is characterized by an increased incidence of premature birth and high perinatal mortality - up to 11-13%. There was also a high incidence of severe postpartum hemorrhage.

Treatment
There is still no medicine that specifically acts on cholestasis. Symptomatic treatment is carried out, the main task of which is to suppress skin itching. For this purpose, it is recommended to use drugs that bind excess bile acids in the blood. First of all, until now cholestyramine has been prescribed for 1-2 weeks.

Currently, ursodeoxycholic acid (ursofalk) is widely used. The drug has a direct cytoprotective effect on the membrane of hepatocytes and cholangiocytes (membrane stabilizing effect). As a result of the drug’s effect on the gastrointestinal circulation of bile acids, the content of hydrophobic (potentially toxic) acids decreases. By reducing the absorption of cholestyramine in the intestine and other biochemical effects, the drug has a hypocholesterolemic effect.

Some researchers, in order to bind bile acids, prescribe antacids from the non-absorbable group (Maalox, Almagel, Phosphalugel) in the usual therapeutic dose for 2-3 weeks. Blind tubes with xylitol, sorbitol, and choleretic drugs from the group of cholecystokinetics are indicated. Antihistamines are usually not effective and are therefore inappropriate to prescribe. Drug metabolism occurs mainly in the liver, so drug overload is extremely undesirable.

Forecast
Intrahepatic cholestatic jaundice in pregnant women is benign in most women; termination of pregnancy is not indicated. However, if pregnancy is complicated by this disease, the patient should be closely monitored by a doctor, monitor liver function, and the condition of the fetus. It is recommended that such women give birth in medical institutions where optimal treatment of the prematurely born child will be provided. In critical situations, if there is a danger to the fetus, premature birth should be induced after 37 weeks of pregnancy.

Cholestatic hepatosis of pregnancy (CHP) is a dystrophic liver lesion caused by the increased sensitivity of hepatocytes to sex hormones and genetically determined enzymopathies, the functional manifestation of which is metabolic disorders of cholesterol and bile acids in hepatocytes, and as a result - a violation of the processes of bile formation and the outflow of bile through the intralobular bile ducts .

SYNONYMS

Idiopathic intrahepatic jaundice of pregnancy, recurrent cholestatic intrahepatic jaundice, intrahepatic cholestasis of pregnancy.
ICD-10 CODE
O26.6 Liver damage during pregnancy, childbirth and the postpartum period.

EPIDEMIOLOGY

The incidence of CGD varies among the populations of different countries and some ethnic groups. CGD is widespread in Chile, Scandinavia, Bolivia, China, and the northern regions of Russia. The reason may be ambiguous diagnosis. For example, in Sweden there are from 1.2 to 40 cases of the disease per 10,000 pregnant women, in Russia - from 10 to 200 (0.1–2%). In Finland, the prevalence of this pathology is 0.5–1%, in Australia - 0.2%. In various subpopulations, the incidence of CGD approaches an average of 1.5%.

The disease can be familial in nature, manifesting during pregnancy with itching and (or) jaundice.

Cholestasis syndrome can develop in women from these families when taking combined oral contraceptives. The literature describes stories of families in which the disease was discovered in grandmothers, mothers, and sisters.

CLASSIFICATION

By severity:
· light;
· medium-heavy;
· heavy.

ETIOLOGY (CAUSES) OF CHOLESTATIC HEPATOSIS IN PREGNANT

The etiology of CGD is not entirely clear. It is believed that genetic factors play a significant role in its development. Women with CGD have a genetically determined increased sensitivity to estrogen.

An increase in estrogen levels in the body of these women leads to the development of cholestasis. Pregnancy in this case plays the role of a trigger factor. Cholestasis, in addition to pregnancy, is observed when taking estrogen-containing oral contraceptives during menstruation, which, given its tendency to recur with repeated pregnancies, also indicates the influence of sex hormones on the development of CGD. It is also suggested that progesterone may be one of the factors causing CGD in women constitutionally predisposed to it. Etiological factors of CGD can be grouped into three groups:

· genetically determined increased sensitivity of hepatocytes and biliary tubules to sex hormones;
· congenital defects in the synthesis of enzymes responsible for the transport of bile components from hepatocytes to the bile ducts;
Congenital defect in the synthesis of bile acids due to enzyme deficiency, leading to the formation
atypical bile acids not secreted by the transport systems of tubular membranes.

PATHOGENESIS

The formation of cholestasis is based on three main pathogenetic factors:
Excessive intake of bile elements into the blood;
· reduction in the amount of secreted bile in the intestine;
· toxic effects of bile components on hepatocytes and biliary tubules.

The rapid increase in the production of sex hormones during pregnancy significantly increases the excretory load on the liver, which, in combination with the congenital constitutional inferiority of the liver enzyme systems, leads to the manifestation of CGD. Estrogens and progesterone are involved in the pathogenesis of CGD. It is known that excess estrogen production can slow down bile flow during normal pregnancy. It has been proven that ethinyl estradiol reduces the fluidity of sinusoidal plasma membranes of hepatocytes. Massive dose of estrogen produced
fetal-placental complex, undergoes metabolic transformations and conjugation in the mother’s liver. At the same time, it has been proven that there is no hyperproduction of estrogens in CGD, and their low concentration in the urine of pregnant women with this pathology confirms the inability of hepatocytes to adequately carry out enzymatic inactivation and conjugation of steroid hormones with glucuronic and sulfuric acids.

Taking into account the level at which the “breakdown” of bile formation occurred, they distinguish:
· intralobular cholestasis, including hepatocellular and canalicular cholestasis;
· extralobular (ductular) cholestasis.

Intralobular cholestasis, one of the varieties of which is considered CHB, can be caused by a decrease in the fluidity of the basolateral and/or canalicular membranes of hepatocytes, inhibition of Na+,K+-ATPase and other membrane transporters, their translocation from the biliary to the sinusoidal pole of the hepatocyte, as well as damage to the hepatocyte cytoskeleton, disruption of integrity tubules and their functions.

In CHB, the pathogenetic factor leading to an excessive concentration of bile components in a hepatocyte is the compaction of its biliary pole, a decrease in the fluidity (absence of pores) of the canalicular membrane of hepatocytes with preserved intracellular transport. The point of application in the development of CGD is the canalicular section of the intrahepatic bile ducts.

It is believed that excessive accumulation of progesterone and other placental hormones in the body inhibits the release of gonadotropic hormones of the anterior pituitary gland. The pituitary gland has a significant influence on the activity of liver enzymes involved in the metabolism of steroid hormones. With a decrease in the function of the pituitary gland, the release of cholesterol by the liver, the synthesis of which increases during pregnancy, as well as bilirubin, is significantly weakened. All this leads to disruption of the processes of bile formation and bile excretion.

Thus, a significant increase in the excretory load on the liver due to an increase in the production of estrogen and progesterone during pregnancy only reveals hidden dysfunctions of this organ. CGD is a manifestation of constitutional deficiency of enzymes that manifests itself during pregnancy as a result of the combined effects of exogenous and endogenous factors.

It should be noted that the development of intrahepatic cholestasis may be based on defects in the synthesis of bile acids themselves in the liver from cholesterol due to a deficiency of synthesis enzymes. The absence of primary bile acids in bile is accompanied by the formation of atypical bile acids that have a hepatotoxic effect, which are not secreted by the transport systems of the tubular membranes and are eliminated through the basement membrane. The diagnostic feature is the absence of an increase in GGT and the detection of atypical bile acids in the urine (atomic spectrophotometry method).

PATHOGENESIS OF GESTATION COMPLICATIONS

CGD increases the risk of preterm birth.

Changes in the synthesis of fetal steroids have been found in pregnant women with CGD. In particular, the ability of the fetal liver to 16-a-hydroxylate DHEAS is reduced with the formation of an inactive metabolite - estriol. As a result, the amount of DHEAS increases, passes into the placenta and is metabolized there along an alternative pathological pathway with the formation of the active hormone estradiol. With CGD, the activity of 16-a-hydroxylase is impaired, the level of estradiol increases, and as a result, premature birth occurs.

An increase in the incidence of postpartum hemorrhage has been reported with CGD. The reason is that the liver's synthesis of coagulation factors II, VII, IX, X is possible only with sufficient vitamin K content in the tissues. Adequate absorption of vitamin K from the intestine depends on the secretion of a sufficient amount of bile acids. Vitamin K deficiency can develop with severe or prolonged cholestasis and can be aggravated by the administration of cholestyramine, which, regardless of cholestasis, causes vitamin K deficiency.

CGD can progress and manifest itself as a significant deviation of liver function indicators from normal values. This may indicate a risk of death for the fetus and the need for emergency delivery. What values ​​of liver parameters should be considered critical, determining the need for active intervention in CGD, remains a dilemma for obstetricians.

CLINICAL PICTURE (SYMPTOMS) OF CHOLESTATIC HEPATOSIS IN PREGNANT

CGD usually debuts in the third trimester (28–35 weeks), with an average of 30–32 weeks of pregnancy.

The leading and often the only symptom of CHB is itching. Its intensity can vary: from mild to pronounced.

Generalized skin itching is described as “excruciating”, “unbearable”. Itching of this intensity leads to excoriation of the skin. Having a tendency to intensify at night, it leads to insomnia, increased fatigue, and emotional disorders. Typical localization of skin itching in CHB is the anterior abdominal wall, forearms, hands, and legs.

Jaundice is considered an intermittent symptom. According to various authors, it is registered in 10–20% of cases. Hepatosplenomegaly, dyspepsia and pain syndrome are not characteristic of CGD (Table 42-1).

Table 42-1. Clinical symptoms of cholestatic hepatosis in pregnant women

Itching and jaundice usually disappear within 7–14 days after delivery, but often return in subsequent pregnancies. In rare cases, CHB takes a protracted course.

For the correct and timely diagnosis of CHB, it is essential to determine the severity of this pathology, since the choice of the optimal management and treatment regimen, as well as the outcome for the mother and fetus, depends on this. The severity of CGD is determined taking into account the most characteristic clinical, laboratory, and instrumental examination data for this pathology. A scoring scale has been developed to assess the severity of CGD (Table 42-2).

Table 42-2. Scale for assessing the severity of cholestatic hepatosis in pregnant women

Criteria for diagnosing CGD	Points
Skin itching:
minor local (anterior abdominal wall, forearms, lower legs)	1
intense local without sleep disturbance	2
generalized with sleep disturbances, emotional disorders	3
Skin condition:
norm	0
single excoriations	1
multiple excoriations	2
Jaundice:
absent	0
subicteric	1
pronounced icterus	2
Increased activity of total alkaline phosphatase, units/l
400–500	1
500–600	2
>600	3
Increase in total bilirubin content, µmol/l
20–30	1
30–40	2
>40	3
Increased activity of aminotransferases (ALT, AST), units/l
40–60	1
60–80	2
>80	3
Increased cholesterol levels, mmol/l
6–7	1
7–8	2
>8	3
Onset of the disease
30–33 weeks	3
34–36 weeks	2
>36 weeks	1
Duration of the disease
2–3 weeks	1
3–4 weeks	2
>4 weeks	3
ZRP
No	0
There is	1

Accounting for results:
· <10 баллов - лёгкая степень;
· 10–15 points - moderate severity;
· >15 points - severe.

COMPLICATIONS OF GESTATION

The prognosis for the mother is favorable, all symptoms disappear 8–15 days after birth. CGD, even with repeated recurrences during subsequent pregnancies, does not leave any changes in the mother’s liver.

Despite the favorable maternal prognosis for CGD, it is more serious for the fetus and is characterized by a high PS. The average rate of perinatal losses in CHB is 4.7%. The risk of fetal death with recurrent cholestasis is 4 times higher than with physiological pregnancy. An increase in the frequency of hypoxia, prematurity, and delayed fetal development to 35% of all births was also noted.

The weight of newborns, both living and stillborn, corresponds to their degree of maturity. Impaired placental perfusion or transfusion is not typical for this disease.

DIAGNOSIS OF CHOLESTATIC HEPATOSIS IN PREGNANT

ANAMNESIS

Pregnant women with CHB experienced miscarriage 2.5 times more often than in the group of healthy pregnant women. Every third pregnant woman with CGD had a history of premature birth or spontaneous termination of pregnancy in the third trimester.

In pregnant women with CGD, the drug history was analyzed, taking into account the use of hepatotoxic drugs before or during pregnancy. Pregnant women with CHB used antibacterial drugs in 93.8% of cases before or during pregnancy. Every second pregnant woman with a history of CGD took combined oral contraceptives.

Pregnant women with CGD, compared to healthy pregnant women, are 2 times more likely to have a history of allergic reactions, mainly to antibacterial drugs (macrolides, erythromycin antibiotics).

Among extragenital pathologies in pregnant women with CHB, diseases of the gastrointestinal tract and endocrine system are most often detected.

PHYSICAL INVESTIGATION

When examining the skin, scratches and abrasions caused by itching are often discovered. Jaundice staining of the sclera, visible mucous membranes, and skin is noted when the bilirubin content increases to more than 30 mmol/l. CGD is not characterized by an increase in the size of the liver, pain or changes in the consistency of this organ.

LABORATORY RESEARCH

Biochemical studies in CGD can detect changes characteristic of cholestasis syndrome.

The most sensitive marker for establishing the diagnosis of CGD is the concentration of serum bile acids, an increase in which is recorded before the appearance of clear clinical and biochemical signs of intrahepatic cholestasis. The bile acid profile in CGD is determined by high-resolution liquid chromatography. It has been established that in CGD there is a significant change in the proportion of primary bile acids: along with an increase in the content of cholic acid (64±3.0%), a decrease in the concentration of chenodeoxycholic acid (20±1.4%) is noted.

Specific and permanent biochemical markers of intrahepatic cholestasis include increased activity of excretory enzymes: alkaline phosphatase, GGT, 5'-nucleotidase. A moderate increase in a- and b-globulins, bilirubin, b-lipoproteins, and triglycerides is noted with a moderate decrease in albumin concentration. Alkaline phosphatase activity and cholesterol content in the blood serum are clearly increased. Alkaline phosphatase activity is increased mainly due to the thermolabile (liver) isoenzyme. An increase in the activity of 5'-nucleotidase and leucine aminopeptidase is also noted. GGT reacts little or may remain within normal limits, unlike other forms of intrahepatic cholestasis.

An increase in aminotransferase activity (ALT, AST) from moderate to significant is noted. With a significant increase in aminotransferases (10–20 times), it is necessary to differentiate from acute viral hepatitis.

Sedimentary samples and proteinogram correspond to those in normal pregnancy. With long-term cholestasis, vitamin K levels correlate with a decrease in prothrombin concentration.

INSTRUMENTAL RESEARCH

For CGD, ultrasound of the liver and biliary tract is used. The size of the liver in this pathology is not increased, the echogenicity of the liver tissue is homogeneous. An increase in the volume of the gallbladder is noted. Splenomegaly is not typical for this pathology.

DIFFERENTIAL DIAGNOSTICS

CGD is differentiated from other liver diseases (Table 42-3).

Table 42-3. Differential diagnosis of cholestatic hepatosis in pregnant women

	CHB	Acute fatty hepatosis of pregnant women	HELLP syndrome*	Viral hepatitis
Pathogenesis	Stagnation of bile	Depletion of detoxification capacity of hepatocytes Immunodeficiency Impaired lipotrophic liver functions	Hemolysis Increased activity of liver enzymes Low number of platelets	Viral lesion of the reticulohistiocytic system and liver parenchyma
Clinical manifestations	Itching Skin excoriation Mild jaundice	Weakness Nausea Heartburn Vomiting Jaundice Abdominal pain	Weakness Petechial rash Jaundice Microangiopathy	Weakness Nausea Vomiting Jaundice Catarrhal symptoms Arthralgia
Laboratory data:
Bilirubin	Increases slightly	Rising	Rising	High
ALT, AST	Promoted	High	Are rising	High
Blood protein	Normal	Short	Short	Short
Dysproteinemia	No	Dysproteinemia	Dysproteinemia	Dysproteinemia
Cholesterol	Promoted	Demoted	Normal	Promoted
alkaline phosphate	Promoted	Promoted	Normal	Promoted
ICE	No	ICE	ICE	ICE
Course of pregnancy and childbirth	Favorable Premature birth FGR Chronic PN	Adverse Urgent termination of pregnancy Antenatal fetal death	Unfavorable Urgent termination of pregnancy	Adverse Antenatal fetal death

*H - hemolysis (haemolyse), EL - elevated liver enzymes, LP - low platelet count.

EXAMPLE OF FORMULATION OF DIAGNOSIS

CHB, mild severity.

TREATMENT OF CHOLESTATIC HEPATOSIS IN PREGNANCY

TREATMENT GOALS

· Relief of symptoms of CHB.
· Relief of symptoms of threatened miscarriage.
· Improvement of uteroplacental blood flow.

NON-DRUG TREATMENT

Efferent therapy is used: plasmapheresis, hemosorption.

Purpose: elimination of pruritogens (compounds that cause itching), bilirubin.

Indications:
generalized skin itching;
· increase in the concentration of primary bile acids, bilirubin, and total alkaline phosphatase activity.

Contraindications:
hypoproteinemia (total protein<60 г/л);
thrombocytopenia (<140´109/л);
· blood diseases (von Willebrand's disease, Werlhoff's disease);
Gastrointestinal diseases (peptic ulcer of the stomach and duodenum, nonspecific ulcerative colitis,
Crohn's disease).

Preparation

Before carrying out efferent therapy, the following studies are mandatory:
· complete clinical blood test with determination of platelet count and Ht indicator;
Determination of blood group and Rh affiliation;
· blood test for syphilis, HIV carriage, HCV, HBSAg;
· determination of serum protein concentration, including albumin.

Methodology and aftercare

The course of efferent therapy includes four plasmapheresis procedures (with an interval of 1–2 days) and one hemosorption procedure.

During each phase of blood sampling, add 1.5 ml of 2.2% sodium citrate solution, and during systemic heparinization - 1.0 ml of this solution. When using a more concentrated 4% sodium citrate solution, add 1.0 ml, and when systemic heparinization - 0.5 ml of this solution.

The amount of plasma removed during one plasmapheresis procedure is about 1/3 of the volume of circulating plasma (on average 600–700 ml of plasma). At the same time, the removed plasma is replaced with isotonic sodium chloride solution at a ratio of 1:1.4. As an anticoagulant, a solution of sodium citrate ACD-A is used, mixed with blood in a ratio of 1:12 with moderate systemic heparinization at the rate of 150 units per 1 kg of body weight.

Hemosorption is carried out through one cubital vein with 3–3.5 liters of blood (about 1 bcc) passing through a sorption column; the dose of pregnant blood entering the system and returned to the vascular bed in one cycle is 9.0 ml of blood. To carry out hemosorption, the system is assembled in the same way as for plasmapheresis, only instead of a plasma filter, a hemosorption column with a slotted filter attachment is used. After completion of the procedure, the blood from the system is completely returned to the pregnant woman’s body.

Calculation of removed plasma

The volume of circulating plasma of an adult with an average body weight is 2.0–2.5 liters. Knowing the BCC, which is 7% of body weight, and the Ht indicator, the volume of circulating plasma is calculated:
1. Volume of circulating plasma = bcc–(Ht´bcc);¸100,
- where the Ht indicator is expressed in %, and bcc and plasma - in ml.
2. Volume of circulating plasma = BCC´(100%–Ht),
Where:
- Volume of circulating plasma = M´Kk,
Where:
- M - body weight (kg);
- Kk - amount of blood per 1 kg of body weight (55–70 ml/kg).
Amount of plasma removed
· Amount of plasma removed = volume of circulating plasma ´П´1.05,
Where:
- P - percentage of the estimated volume of plasma removed;
- 1.05 - coefficient for taking into account the hemopreservative.

Replenishment of removed plasma

The ratio of the volume of removed plasma to the volume of plasma replacement solutions is 1:1.5–1:2.

Protein preparations (albumin, protein), as well as solutions of amino acids, colloids (gelatin, rheopolyglucin©, hemodez©), and saline solutions are used as plasma substitutes for pregnant women. With any of the methods, after removing the plasma, the condensed cellular mass of blood is diluted with isotonic sodium chloride solution or another plasma substitute and returned to the patient. In one session, from 1/3 to 1/2 of the volume of circulating plasma is removed.

If it is necessary to exfusion large volumes of plasma (20% of the volume of circulating plasma or more), single-needle membrane plasmapheresis is performed. The advantage of this method is the small volume of the extracorporeal circuit (up to 60 ml), the use of only one vein. The line with the plasma filter is filled with isotonic sodium chloride solution and sodium citrate solution with 5000 units of sodium heparin, the bottles with which are secured in special racks; 10,000 units of sodium heparin are administered to the patient intravenously before connecting to the device.

The volume of the removed filtrate, containing the patient’s plasma and anticoagulant solution, is 0.75–1.0 l per 1 hour.

DRUG TREATMENT OF CHOLESTATIC HEPATOSIS IN PREGNANT

Artichoke leaf extract (chophytol©), hepabene© are used as hepatoprotectors and choleretics.

For mild CHB, hofitolª and hepabene© are prescribed orally, 1 tablet 2-3 times a day before meals for 14-21 days. For moderate and severe CHB, therapy should begin with intravenous administration of hophytol© 5.0 ml per 400 ml of isotonic sodium chloride solution. Parenteral administration of hofitol© - daily for 10–14 days.

In addition to hepatoprotectors of plant origin, the drug ademetionine is used. For mild CGD, it is prescribed orally at a dose of 400 mg 2 times a day between meals for 2–3 weeks. For moderate and severe CGD, ademetionine is prescribed in a two-stage regimen: first intravenously (slow stream or drip in 200 ml of isotonic sodium chloride solution) at a dose of 400 mg per day once for 7–10 days. Then pregnant women with CGD are transferred to oral administration of the drug, 400 mg twice a day for 1–2 weeks. Ursodeoxycholic acid preparations - Ursosan© or Ursofalk© - are prescribed simultaneously with hepatoprotectors. The drug ursodeoxycholic acid is prescribed 1 capsule 2 times a day for 2–3 weeks.

The following antioxidants are recommended for all forms of CGD: tocopherol acetate (vitamin E) 1 capsule 2 times a day, ascorbic acid 5% 5.0 ml intravenously in 20 ml of 40% glucose daily for 10–14 days. For moderate and severe CGD, intravenous drip of sodium dimercaptopropanesulfonate (unithiol©) 5.0 ml in 400 ml of isotonic sodium chloride solution once daily for 1–2 weeks.

To interrupt the pathological enterohepatic circulation and bind excess bile acids in the intestine, a natural polymer of plant origin - hydrolytic lignin (polyphepan©) is prescribed as an enterosorbent. Polyphepan© is prescribed 10 g 2 times a day for 1–2 weeks.

SURGERY

Surgical treatment is not indicated.

PREVENTION AND PREDICTION OF GESTATION COMPLICATIONS

In order to prevent the development of CGD, it is advisable to:
· identification of pregnant women from risk groups, taking into account:
- presence of CGD in close relatives in the family;
- CGD in previous pregnancies;
- chronic gastrointestinal diseases;
· use of hepatoprotectors, choleretics, antioxidants for pregnant women at risk for the development of this pathology before the appearance of the first clinical signs of the disease;
· exclusion of hormonal and antibacterial agents;
· dieting.

The most unfavorable prognosis for CGD is observed with severe icteric and cytolytic syndromes, with early (25–27 weeks) development of the disease.

FEATURES OF TREATMENT OF GESTATIONAL COMPLICATIONS

Treatment of gestational complications by trimester

When symptoms of threatened miscarriage appear in the 2nd–3rd trimesters, infusions of magnesium sulfate, antioxidants, and beta-adrenergic agonists are used.

In order to improve uteroplacental blood flow, infusions of meldonium (mildronate©), 5% glucose, Actovegin© are performed.

Treatment of complications during childbirth and the postpartum period

During childbirth, the use of antioxidants is recommended (infusion of 5% glucose with ascorbic acid 5.0 ml, unithiol© 5.0 ml). In the afterbirth period - etamsylate 4–6 ml intravenously, menadione sodium bisulfite (vicasol©) 3 ml intravenously.

In the postpartum period, it is also necessary to continue taking hepatoprotectors and choleretics for 7–14 days after delivery in the most severe forms of CGD.

INDICATIONS FOR CONSULTATION WITH OTHER SPECIALISTS

· Consultation with an infectious disease specialist is indicated when aminotransferase activity (ALT, AST) and bilirubin concentration increase by more than 2–3 times in order to exclude viral hepatitis.
· Consultation with an endocrinologist - if there is skin itching of any intensity (excluding diabetes).
· Consultation with a dermatologist - if there are excoriations of the skin (excluding dermatitis, scabies, eczema, etc.).
· Consultation with a therapist - for all manifestations of CGD (exclusion of other diseases of the hepatobiliary system).

INDICATIONS FOR HOSPITALIZATION

· The appearance of skin itching and biochemical markers of cholestasis.
· Increased skin itching with normal biochemical parameters.
· The first manifestations of CGD in pregnant women at risk for the development of this pathology.
· Presence of symptoms of cholestasis and threat of miscarriage.
· Presence of symptoms of cholestasis, signs of placental insufficiency and/or FGR.
· For carrying out efferent therapy.

ASSESSMENT OF TREATMENT EFFECTIVENESS

· Disappearance of skin itching or reduction in its intensity, improved sleep.
· Decrease in the content of primary bile acids, activity of total alkaline phosphatase, GGT, ALT, AST, bilirubin.
· Disappearance of symptoms of threatened miscarriage.
· Reducing the incidence of miscarriage and perinatal complications.

CHOICE OF DATE AND METHOD OF DELIVERY

· Early delivery (up to 37 weeks) is indicated in the case of severe CGD with an increase in the intensity of itching, jaundice and bile acids in the presence of fetal dysfunction.
· If the therapy has a positive effect, delivery is indicated at 38 weeks.
· In the absence of signs of fetal dysfunction, delivery through the natural birth canal is possible.

INFORMATION FOR THE PATIENT

· Compliance with a diet excluding fatty, fried, spicy foods and alcohol.
· The use of combined oral contraceptives is not recommended.
· Monitoring of biochemical blood parameters (total alkaline phosphatase, bilirubin, ALT, AST, cholesterol) 1–2 weeks after delivery and subsequently once a year.
· Observation by a hepatologist. Ultrasound of the liver and biliary tract once every 2–3 years.
· Determination of markers of cholestasis in subsequent pregnancies, starting from the early stages.
· Careful use of antibacterial drugs. Combined use of antibiotics with hepatoprotectors.