LIVER DISEASES

HEPATITIS AND PREGNANCY

Acute viral hepatitis – the most frequent disease which is followed by an icterus, isn't bound with pregnancy. Now but to an etiological sign distinguish several options of an acute viral hepatitis: viral hepatitis A (VHA), viral hepatitis B(VHB), viral hepatitis C (VHC), viral hepatitis of V (VGV) and viral hepatitis E (VHE).

 

VIRAL HEPATITIS A (VHA)

Infecting agent is the hepatitis A virus. To sources of an infection serve the person sick with a viral hepatitis of A. Infektion is given in the fecal and oral way therefore in spread of an infection the large role is played by sanitary and hygienic living conditions of the population. Transfer of VGA from mother to a fetus doesn't exist as the virus doesn't pass through a placenta. Children of the first year of life aren't ill VGA, they are immune, received from mother, further these antibodies disappear. The people who had VGA gain resistant immunity.

Clinic. The disease proceeds cyclically. The incubation (asymptomatic) period proceeds from 1 week to 50 days, 15-30 days are more often. The prodromal (anicteric) stage proceeds from 2 to 14 days, the thicket is 5-7 days old. Dispepsial and asthenoneurotic syndromes are inherent in it, there is morbid a liver and a lien. Body temperature increases, the level of transaminases is enlarged, there is an icterus, the feces becomes colourless, urine darkening becomes perceptible. In blood serum a direct bilirubin is enlarged. Hepatitis is followed by a leukopenia (pregnant women can have also a leukocytosis), a lymphopenia, a low ESR. In the period of a convalescence clinical and biochemical signs of illness are gradually normalized. Convalescence occurs in 4-6 weeks. Chronic forms don't develop.

Diagnostics: definition of antibodies to a hepatitis A virus. At anicteric option of VGA there are all clinical and biochemical signs of illness except an icterus and a hyperbilirubinemia. VGA in most cases proceeds safely.

Influence of VGA on the course of pregnancy and labors: pregnancy not incubation, in the II-III trimesters of pregnancy risk is higher, than in the first. Labors in an acute stage of VGA don't threaten the parturient woman with any complications bound to hepatitis:

- at the time of delivery in an acute stage of VGA the fetus always is in a condition of a hypoxia which that bigger, than is deeper a prematurity of a fetus

- when maintaining labors in an acute stage of VGA the last are always conducted as premature

- viral hepatitis  A in all stages of a disease isn't contraindication for a delivery by Cesarean section (according to strict obstetric indications), but preference should be given to a delivery in natural patrimonial ways.

- if labors occurred in an acute stage of VGA, it increases risk of puerperal inflammatory diseases at the puerpera and risk of a post-natal case rate at the newborn.

In the second half of pregnancy usually hepatitis proceeds heavier, than in the first. Labors pass without features, and additional actions aren't required. The child will be born healthy. It isn't subject to risk of a becoming infected of VGA and doesn't need special prophylaxis.

From the moment of emergence of an icterus in pregnant, sick VGA, it stops being dangerous to people around, and her child isn't dangerous to other children of unit of newborns. VGA belongs to the self-limited (self-recovering) infections therefore medicamental therapy isn't required, it is possible to be limited to a medical and protective regimen and a diet.

 

ACUTE VIRAL HEPATITIS B (VHB)

proceeds much heavier, than VGA, and constitutes larger danger to the woman and her fetus.

The originator of hepatitis B is transferred from the patient or a virus carrier with a blood and all biological liquids: semen, saliva, urine, milk. The general toothbrush or the razor are dangerous. The risk of a disease is especially high at children up to 2 years, adult 40 years and pregnant women are more senior

Clinic. The disease develops cyclically. The incubation interval of VGV proceeds of 6 weeks up to 6 months. The prodromal stage is also longer, than at VGA. 1-4 weeks and more. There are asthenic and dispepsial disturbances, there are an urticaria eruption, arthralgias. Temperature increases seldom. The hepatosplenomegaly is observed. More considerably, than at VGA, the level of transaminases is enlarged. With the advent of an icterus which proceeds 1-3 months the condition of the patient worsens, intoxication amplifies (unlike VGA). There are hemorrhages.

Acute VGB can proceed as with clinical implications (icteric and anicteric options), and without them (inapparantny option). Infection not always leads to development of a clinical picture of illness, a healthy chronic carriage of virus can be observed.

From laboratory indicators paramount value has depression of an prothrombin index (<50%) rising of level of a bilirubin, increase of a leukocytosis, neutrocytosis and ESR.

The course of pregnancy and labors at VGB: toxicoses, a preeclampsia, bleedings, not incubation of pregnancy, anomaly of patrimonial activity, a small-for-date fetus, puerperal is purulent - septic diseases, activation of a fetal microflora leads to rising of a case rate of newborns.

The viral hepatitis B poses a real threat for life of the woman, a fetus and the newborn. The aggravation of symptoms in the second half of pregnancy can be complicated by an acute liver failure with encephalopathy and a coma, with a high lethality.

Breastfeeding isn't contraindicative as almost extremely seldom the infection is transmitted with mother's milk.

Diagnostics. In most cases the diagnosis of VGV can be correctly made on the basis of clinical laboratory indicators. Verification of the diagnosis is made by determination of serological criteria. HBsAg. Absence of HBsAg doesn't allow to reject the diagnosis if there are other signs of illness since for its definition rather sensitive methods aren't always used.

Treatment. A dietetics without essential drug treatment. At a severe form of acute VGV there is a need for medicines: disintoxication therapy, antioxidants, anticoagulants, infusional therapy. At bleeding apply freshly frozen plasma and a blood.

 

ACUTE VIRAL HEPATITIS C (VHC)

Viral Hepatitis C (VHC) of a way of transfer sexual, parenteral, vertical.

After a becoming infected three options of a course of a disease are possible:

1) Convalescence as a result of destruction of a virus own immune system

2) The most frequent way of a course of a disease – initially chronic current with gradual formation of cirrhosis, a hepatocellular carcinoma

3) In a small number of cases of VGC begins with an acute disease, then hepatitis from the very beginning proceeds hard and the risk of the most dangerous complications of pregnancy sharply increases, especially if in an acute stage of illness there is abortion.

Clinic. The incubation interval proceeds from several days to 1 year and more longly, but is more often of 2 weeks up to 3 months. The prodromal stage is characterized by gradually appearing delicacy, nausea, a loss of appetite. There are no symptoms of intoxication in this period. Anicteric options of illness prevail, the icterus appears only at 5% of patients. Intoxication is expressed poorly. Level of transaminases increases, but it isn't so appreciable, as at VGB. Fulminant forms are rare, develop only at persons with an immunodeficiency or with chronic illnesses of a liver. The convalescence period not always comes to an end with convalescence of the patient. At 50-70% of patients the disease accepts a chronic current, and chronic active hepatitis with the subsequent transformation in cirrhosis is in most cases formed. Approximately at 30% of patients within 20 years cirrhosis and at 10% from them – a hepatocellular carcinoma develops.

The course of pregnancy and labors at VGC: at pregnancy of VGC, as well as VGA, doesn't exert special impact on the course of gestational process. In view of that hepatitis C can be bound to a narcomania, the forecast at the pregnant woman in an acute stage is extremely adverse. However such combination meets seldom. Actions of the obstetrician in an acute stage of VGC at the pregnant woman same, as at a severe form of a viral hepatitis B: the prevention of abortion, maintaining labors in any duration of gestation as premature, prophylaxis and treatment of puerperal complications. The perinatal mortality at VGC which began sharply is extremely high.

Diagnostics. Definition of RNA of a virus of hepatitis C (RNA-HCV) in blood serum in 1-2 weeks after infection. For confirmation of the clinical diagnosis of VGS also definition of antibodies to HCV is used. But as at a viral hepatitis From an antibody to HCV are taped only in 2 months, their definition has larger diagnostic value at chronic hepatitis.

Treatment. Therapy of VGC at pregnant women same as treatment of VGA and VGB. Treatment by an interferon at pregnant women isn't applied.

 

ACUTE VIRAL HEPATITIS E (VHE)

The Viral Hepatitis E (VHE) is allocated from group of a viral hepatitis with the fecal and oral mechanism of a transmission of infection. A virus of hepatitis E (HEV) - RNA-viruliferous which antigenic structure is still insufficiently established. The chronic carriage of the VHE virus and chronic forms of illness doesn't exist. The women who transferred VGHE gain strong immunity.

At nonpregnant VHE proceeds mainly easily, and at pregnant women exclusively hard: 20% of patients perish if the disease arises in the second half of pregnancy. Fulminant development of an acute liver failure during pregnancy arises at 10-30%. The lethality at VHE in the II-III trimesters is 25-30 times higher, than at VGB. Gravity of symptoms of fulminant hepatitis increases with augmentation of duration of gestation; usually the disease gets a fulminant current after 24 weeks of pregnancy. The highest frequency of this form is observed in the last trimester of pregnancy and even at the time of delivery. The sharp aggravation of symptoms occurs on the eve of labors or an abortion. Fulminant hepatitis leads to spontaneous abortion (abortions, premature births), the development of a hepatocellular coma within 1-2 days expressed to Disseminated intravascular coagulation syndrome  with the raised hemorrhage in labors, frequent antenatal death of a fetus.

Usually the disease develops sharply or violently, during the first 1-3 days serious intoxication is observed. Acute hepatic encephalopathy and a hepatocellular coma arises no later than the 17th day of illness. 45% have a renal failure. One of the most precursory symptoms of an aggravation of symptoms – a haemoglobinuria which appears at 96% of patients.

Danger of a lethal outcome remains and after the delivery, especially in the first week.

Feature of severe forms of VHE is the intravascular hemolysis of erythrocytes owing to the DIC with development of a renal liver failure. Hemolysis of erythrocytes is followed by a haemoglobinuria, damage of a renal canaliculus, an oliguria with the subsequent uremia. At the same time there is a liver necrosis, the acute liver failure with encephalopathy progresses.

Features of a course of pregnancy and labors: the beginning of a late misbirth or labors coincides usually with fetal death of a fetus, similar outcomes are caused by a fetal infection of VHE. Process of abortion in an acute stage of VHE never happens long, labors or late abortion proceed no more than 4-5 hours. 41% of women have hemorrhagic complications in labors and the early puerperal period. The IDCS is the reason of bleedings not only uterine, but also gastrointestinal, pulmonary, nasal, quite often lethal.

For the woman who endured acute hepatic encephalopathy, abortion, the IDCS there is a high risk of a serious inflammatory illness and obstetric bleedings in the late puerperal period, and also the long time remains danger of a serious renal failure.

Treatment. Therapy of VHE at pregnant women same as treatment of VGA and VGB. For prophylaxis and treatment of a hemorrhagic syndrome use a heparin, Trentalum, Dicynonum, transfusion of freshly frozen plasma, a platelet concentrate.

In the acute period of VH abortion, irrespective of duration of gestation, medical indications and desire of the woman is absolutely contraindicative. The acute stage of VH comes to an end in the presence of clinical and laboratory signs of convalescence i.e. when there comes the convalescence period. It is better to make abortion at this particular time.

 

At VH the issue of abortion is resolved individually in each separate case. The basic rules by which it is necessary to be guided at the same time, the following:

1) At the mild and medium-weight course of an acute viral hepatitis of any etiology with which the woman got sick in the I trimester of pregnancy it should be kept. The disease of this severity isn't the indication for medical abortion. The risk of congenital anomalies at an acute viral hepatitis in the I trimester of pregnancy isn't higher, than at healthy pregnant women.

2) At the serious course of an acute viral hepatitis in the I trimester of pregnancy it is possible to recommend discontinuing it on medical indications, especially at a lingering or wavy current of the period of a convalescence.

3) The acute viral hepatitis of any etiology and severity postponed in the II trimester of pregnancy isn't the indication for medical abortion.

4) If the woman insists on abortion, it is necessary to postpone it until the termination of an acute stage of a viral hepatitis. For the woman it is safer if abortion is carried out in the convalescence period, i.e. it isn't obligatory up to 12 weeks of pregnancy. It is better to undergo this operation for the term of 19-20 weeks of pregnancy.

 

CHRONIC HEPATITIS AND PREGNANCY

Chronic hepatitis is defined as the diffuse polyetiological inflammatory process in a liver continuing without improvement for 6 months and evolving or not evolving in cirrhosis.

Chronic hepatitis are generally divided into chronic persistent and chronic active (aggressive) – HAG. This classification is based on the morphological principle. For clinical practice by drawing up the diagnosis also etiological factor (chronic viral, autoimmune, alcoholic, medicinal hepatitis) is specified. It helps to define quicker the course of a disease and feature of its therapy. The most common form of chronic hepatitis (67-70%) is the hepatitis of a virus etiology which developed owing to the hepatitis B or C postponed earlier. Now most often (in 50%) chronic hepatitis C meets.

Chronic hepatitis in combination with pregnancy meets seldom, it substantially has a talk disturbance of menstrual function and sterility at women with such pathology. The illness is more serious, the chance of sterility is higher. At the same time reports on development of pregnancy in the patients having chronic hepatitis are even more often published in literature.

Clinic. The main clinical signs of chronic active and persistent hepatitis at pregnant women are shown by cholestasia symptoms, dispepsial, asthenoneurotic symptoms, arise a cytolytic syndrome later (an exit of desmoenzymes: ALAT, ASAT, LDG) and a hepatocellular failure (the hypoalbuminemia, a hypochilesterinemia, a prothrombinopenia, hyper-or a hypoglycemia, is broken a metabolism of endogenic hormones, there is an azotemia and as the final - a hepatic coma). The hemorrhagic syndrome is in certain cases observed. The hepatomegalia appears later, however it sometimes is expressed slightly or is absent absolutely. The splenomegaly is found in 40-50% of patients.

At a biochemical blood analysis substantial increase of activity of aminotransferases is defined (at 5-10 times, but not less, than twice twice at an interval of a month), activity of GGT, alkaline phosphatase, 5 nucleotidases is enlarged. Most of patients has a hyperbilirubinemia, a disproteinemia, anemia, a leukocytosis, rising of an ESR.

In a stage of remission of a disease all clinical, biochemical and morphological features partially or completely disappear.

Many researchers hold the opinion that to women, sick chronic active hepatitis with moderately expressed activity and especially adversely proceeding form, it is recommended to abstain from pregnancy.

Chronic hepatitis exerts adverse impact on the course of pregnancy and its outcome: the high risk of a maternal mortality, spontaneous abortions, preeclampsias, premature births, a perinatal mortality takes place. Pathology of a fetus is expressed in signs of a fetal hypoxia, an oligotrophy and a prematurity owing to a placental failure.

To the women suffering from HAG, pregnancy is contraindicative. At chronic hepatitis in a stage of permanent remission it isn't obligatory to interrupt pregnancy. Tactics of maintaining patients with chronic active hepatitis at offensive of pregnancy has to consider a possibility of its exacerbation after the abortion made in any time, and also a possibility of an infection with a virus of hepatitis In the children who were born at mothers sick with chronic active hepatitis of a virus etiology.

 

CHOLESTATIC HEPATOSIS OF PREGNANT WOMEN

The Cholestatic Hepatosis of Pregnant Women (CHPW) — the dystrophic lesion of a liver caused by a hypersensibility of hepatocytes to sex hormones and genetically determined fermentopatiya, which implication — disturbances of exchange of a cholesterin and bile acids in hepatocytes, and thereof — disturbance of processes of biliation and outflow of bile on intralobular cholic ducts.

Mark out 3 severity of CHPW:

• mild;

• medium-weight;

• severe.

Etiological factors of CHPW can be united in three groups:

1) genetically caused hypersensibility of hepatocytes and the biliary of a canaliculus to sex hormones;

2) congenital defects of synthesis of the enzymes responsible for transport of components of bile from hepatocytes in cholic ducts;

3) the congenital defect of synthesis of bile acids owing to deficiency of enzymes leading to formation of the atypical bile acids which aren't cosecreted by transport systems of canalicular membranes.

Formations of a cholestasia are the cornerstone three major pathogenetic factors:

1) excessive entering of elements of bile in a blood;

2) depression of amount of the cosecreted bile in an intestine;

3) toxic impact of components of bile on hepatocytes and biliary canaliculus.

Fast rising of production of sex hormones at pregnancy considerably strengthens an excretory load on a liver that in combination with congenital constitutional inferiority of ferment systems of a liver leads to CHPW manifestation. Estrogens and progesterone are involved in a pathogenesis of CHPW. It is known that excess production of estrogens can slow down bile current at normal pregnancy. It is proved that ethenyloestradiolum reduces flowability of sinusoidal plasmatic membranes of hepatocytes. The massive dose of estrogens produced by a fetal-placental complex is exposed to metabolic transformations and conjugation in mother's liver. At the same time it is proved that there is no hyperproduction of estrogens at CHPW, and their low concentration in urine at pregnant women with this pathology confirms disability of hepatocytes adequately to carry out an enzymatic inactivation and a conjugation of steroid hormones with glucuronic and sulfuric acids.

The course of pregnancy at CHPW:

CHPW increases risk of premature births (synthesis of steroids of a fetus at which Oestradiolum level increases is broken, and premature births result).

At CHPW note augmentation of cases of puerperal bleeding (synthesis of factors of coagulation depends on the content of vitamin K which absorption in an intestine at patients with CHPW is reduced owing to deficiency of bile acids).

 

Clinical picture:

CHPW usually debuts in the third trimester (in 28–35 weeks), on average — on 30–32 week of pregnancy. The leading and often only symptom at CHPW — a dermal itch. Its intensity can be different: from mild to expressed. The generalized dermal itch is described as "excruciating", "intolerable". The itch of such intensity leads to excoriations of integuments. Tending to intensifying at night, leads to sleeplessness, increased fatigue, emotional disorders. Typical localization of a dermal itch at CHPW — a forward abdominal wall, forearms, hands, anticnemions.

The icterus is carried to changeable symptoms. According to different authors, it is recorded in 10–20% of cases.

The hepatosplenomegaly, dyspepsia and pain syndrome aren't characteristic of CHPW.

The itch and icterus usually disappear after the delivery within 7–14 days, but often renew at the subsequent pregnancies. In rare instances CHPW accepts a lingering current.

The forecast for mother favorable, all symptoms disappear in 8–15 days after the delivery. CHPW, even at a repeated relapse during the subsequent pregnancies, doesn't leave any changes in mother's liver.

Despite the favorable maternal forecast at CHPW, for a fetus it more serious is also characterized by a high perinatal mortality. Frequency of perinatal losses at CHPW averages 4,7%.

 

Diagnostics:

1) The anamnesis (not incubation of pregnancy in the anamnesis is characteristic; reception of oral contraceptives, allergic reactions to antibacterial drugs, gastrointestinal diseases and endocrine system).

2) Physical research. At survey of integuments find the raschesa and grazes caused by an itch. An icteric staining of the scleras visible mucous, skins note more than 30 mmol/l when rising maintenance of bilirubin. The augmentation of the sizes of a liver, morbidity or change of a consistence of this organ isn't characteristic of CHPW .

3) Laboratory researches: at CHPW  there is a rising of content of cholic acid and depression of concentration of deoxycholic acid. Refer rising of activity of enzymes to specific and constant biochemical markers of an intra hepatic cholestasia: alkaline phosphatase, GGT, 5 ’-nucleotidases, moderate rising of a-and b-globulins, a bilirubin, b-lipoproteins, triglycerides at moderate depression of concentration of an albumin. Rising of activity of aminotransferases (ALT, nuclear heating plant) from moderated to appreciable becomes perceptible. At a long cholestasia the content of vitamin K correlates with depression of concentration of a prothrombin.

4) Tool researches: US of a liver and biliary tract.

 

Treatment:

Apply efferent therapy: a plasma exchange, hemosorption (at a generalized itch, bilirubin increase, rising of alkaline phosphatase).

Gepatoprotektora and choleretics (drugs of ursodezoksikholevy acid —  since increase conjugation of bile acids).

For discontinuing of pathological enterogepatichesky circulation and binding of excess of bile acids in an intestine – enterosorbents (Polyphepanum).

 

Choice of term and method of a delivery: the early delivery (up to 37 weeks) is shown in case of a serious current of HGB with increase of intensity of an itch, icterus and content of bile acids at disturbance of vital activity of a fetus. At positive effect from the carried-out therapy the delivery is shown in 38 weeks. In the absence of signs of disturbance of vital activity of a fetus the delivery in natural patrimonial ways is possible.

 

Hepatocerebral dystrophia of a liver and pregnancy

hepatotserebral dystrophia (Wilson-Konovalov's illness) – the chronic progressing disease inherited on autosomal recessively type. Illness is caused by disturbance of exchange of copper and protein and is characterized by the combined lesion of a liver, central nervous system, kidneys and eyes.

For the first time the disease is described by the English neuropathologist Wilson in 1912 and called by it "a hepatolenticular degeneration". Then this pathological syndrome was studied by N. V. Konovalov and in more detail described in 1960 under the name a hepatocerebral dystrophia. Prevalence of illness makes 1:500-1:200. Meets more often in districts where the percent of marriages between condanguinity relatives, for example, in the western districts of Ukraine and Belarus is high.

The pathogenesis of a disease is bound to genetic defect of synthesis of a hepatocuprein that leads to copper exchange disturbance. The balance of copper in an organism is supported by daily reception of 2 mg with a nutrition and easily reached even at rather poor copper to a diet. A hepatocuprein - serumal protein of a2-globulinovy fraction. It is synthesized in a liver, concentration it in a blood out of pregnancy makes 0,2-0,3 g/l. Each molecule of a hepatocuprein binds 8 atoms of copper. Thus, 95% of serumal copper are in the connected look.

As a result of disturbance of synthesis of a hepatocuprein copper is only рыхло bound to an albumin and amino acids, is easily split off from them, in a large number is emitted with urine and laid in tissues, generally in a liver, partially in a brain, a cornea of eyes. Excess of free copper oppresses activity of oxidizing and some other enzymes that leads to death of cells.

 

Clinic: Wilson-Konovalov's illness begins at children's and young age. Distinguish three stages of a disease:

• preclinical

• visceral

• neurologic

More often emergence of symptoms of a lesion of a nervous system is preceded by visceral disorders in the form of disturbance of activity of a liver, the hepatolienal syndrome is quite often observed. The lesion of a liver becomes perceptible at all forms of a hepatocerebral dystrophia. Degree of a lesion of a liver is in direct dependence on disease duration. Within the first 3 years chronic active hepatitis with an icterus, high activity of aminotransferases, a giperuglobulinemiya develops. At prescription of illness more than 9 years cirrhosis with a portal hypertension and a hepatocellular failure develops.

Pathology of a nervous system is characterized by disturbance of mentality and extrapyramidal disorders in the form of a muscular rigidity, hyperkinesias. A typical symptom of illness – adjournment of the greenish and brown pigment containing copper on the periphery of a cornea of eyes (Kayser-Fleischer's ring). At some patients the lesion of kidneys (a pyelonephritis, a glomerulonephritis) becomes perceptible, however the renal failure at them isn't observed.

Diagnostics: clinical signs of a lesion of a liver, a nervous system, detection of a ring of Kayser-Fleischer in an eye cornea, depression of a hepatocuprein in blood serum (less than 0,2 g/l), copper egestion augmentation with urine (more than 100 mkg a day). In diagnostically hard cases the puncture biopsy of a liver (in punctates rising of concentration of copper becomes perceptible) is shown.

During pregnancy copper exchange changes. Since sixth week and to the labors the content of copper in plasma of pregnant women is gradually enlarged. To the pregnancy extremity it doubles. Rising of level of copper is bound to the increasing secretion of estrogens. The copper egestion with urine at physiological pregnancy and a preeclampsia doesn't change, but raises by 6 times at a serious preeclampsia. Excess release of copper in these cases is bound to a proteinuria. Protein carries out transport of copper together with which it is allocated.

Treatment: lifelong reception of O-Penicillaminum (Cuprenilum) of 300-600 mg a day. Drug binds ions of copper and removes them with urine.

In literature there are infrequent reports on a combination of illness of Wilson-Konovalov to pregnancy. This results from the fact that at such patients disturbance of menstrual function and sterility is often observed.

The question of admissibility of pregnancy at women is put with Wilson-Konovalov's illness and can't unambiguously be solved. Pregnancy is contraindicative to patients in a neurologic stage of a disease, at severe damages of a liver (active hepatitis, a cirrhosis), kidneys, to the women who aren't receiving treatment by V-Penicillaminum.