Viral hepatitis in pregnancy is a group of infectious diseases with predominant damage to liver tissue caused by hepatotropic viruses and detected during gestation. They are manifested by severe intoxication, jaundice, dyspepsia, a change in the color of urine and feces, an increase in the liver. They are diagnosed using ELISA, RIF, PCR, laboratory studies of enzyme systems, pigment, protein, fat metabolism, supplemented by a general blood test and liver ultrasound results. For treatment, infusion therapy, hepatoprotectors, choleretic drugs are used in combination with a therapeutic and protective regime and diet therapy.
O98.4 Viral hepatitis complicating pregnancy, childbirth or the postpartum period
Viral hepatitis is detected in 0.2-3.0% of pregnant women, in 40-70% of cases, jaundice during gestation is caused by viruses. More than half of the patients are diagnosed with viral hepatitis B, the acute form of the disease occurs with a frequency of 1-2 cases per 1000 pregnancies, chronic — 5-15 per 1000. The second most common is hepatitis A, the third is C, which has recently been increasingly detected during the gestation period. As a result of research, it was found that, all other things being equal, pregnant women who fall into the focus of infection become ill 5 times more often than other people. Risk factors are young age, low income, poor material and living conditions, promiscuous sex life, living in epidemiologically unfavorable countries with low availability of quality medical care.
The etiology of viral hepatitis in pregnancy is the same as in other cases. The causative agents of the disease are RNA and DNA-containing viruses of different types: A (HAV), B (HBV), C (HCV), D (HDV), E (HEV). In recent years, experts in the field of infectious diseases have reported a possible role in the development of hepatitis viruses F, G, SEN V, TTV, etc. Pregnant women are increasingly diagnosed with mixed hepatitis, which is provoked by several pathogens and often more severe. There are several risk factors that increase the likelihood of infection during pregnancy. Their role increases significantly if the rules of hygiene, asepsis, antiseptics are not observed:
- Stay in a medical institution. A pregnant woman is hospitalized in a hospital before childbirth, if obstetric complications occur, if there is a serious extragenital pathology. In territories and countries where there are problems with hygiene and sanitation, fecal-oral infection of the patient with viral hepatitis A, E and even the occurrence of intrahospital epidemics is possible.
- Performing invasive manipulations. If the norms of asepsis and antiseptics are violated, the risk of infection with hepatotropic viruses with parenteral transmission becomes a serious problem. A pregnant woman can become infected by using contaminated instruments, installing droppers, applying forceps, performing invasive prenatal examinations, surgical interventions.
- Blood transfusion. There are a number of conditions that require blood transfusion and its components. Hemotransfusion therapy is prescribed for massive bleeding, DIC syndrome, severe anemia, hemorrhagic shock, postpartum sepsis. Although careful blood quality control minimizes such risks, infection is possible in emergency situations when working with unverified donors.
The mechanism of development of the pathological process depends on the characteristics of the pathogens. Most viral liver inflammations are severe anthroponoses, only pigs and rodents can be a natural reservoir for the HEV virus. The incubation period lasts from 15-50 days for hepatitis A and C, 20-80 days for infection with hepatitis D, E to 40-120 days for hepatitis type B. In the case of infections with alimentary and aqueous modes of transmission, the entrance gate is the mucous membrane of the gastrointestinal tract, through which the viral agent replicates in the mesenteric lymph nodes and endothelium of the vessels of the small intestine. With the blood flow, the pathogen spreads through the body, which is clinically manifested by intoxication syndrome, after which it enters the liver. With sexual, parenteral, vertical transmission mechanisms, the pathogenic agent immediately enters the bloodstream, and then through the blood into the liver.
All types of hepatotropic viruses, except HBV serotypes, have a direct cytopathic effect and cause cytolysis of hepatocytes. The damaging factor in the development of viral hepatitis B is an enhanced immune response with inflammation and necrobiotic processes. Replication of the HDV virus requires an assistant virus, which becomes the causative agent of hepatitis B. A pregnant woman develops clinical and laboratory signs of cytolytic, cholestatic, mesenchymal-inflammatory biochemical symptom complexes. The pathogens of hepatitis A and E from the destroyed liver cells enter the bile and are further excreted into the environment, polluting it. HBV, HCV and HDV viruses continue to circulate in the blood.
Self-elimination of the pathogen due to high immunogenicity occurs when infected with hepatitis B pathogens (with a normal immune response), A, E. HDV are eliminated after the disappearance of HBV, without which further replication of the virus is impossible. Due to the high mutation rate, the causative agent of hepatitis C has low immunogenicity, which is associated with the chronic progressive course of the disease. Chronization of the disease is also possible with a weak immune response to the HBV virus, mutation of the pathogen, integration of viral DNA into the genetic apparatus of the hepatocyte, insufficient synthesis of α-interferon, the occurrence of autoimmune reactions.
The systematization of forms of viral hepatitis in pregnancy is carried out taking into account the same criteria as outside the gestational period. According to the severity of clinical manifestations, there are subclinical, mild, medium, severe, fulminant (lightning-fast) variants of viral hepatocyte damage. Along the course, the disorder can be acute, prolonged, chronic. The classification according to the mechanism of transmission of the pathogen plays the greatest importance for the choice of medical tactics. Infectious disease specialists distinguish:
- Hepatitis with fecal-oral infection. This group includes infectious processes caused by viruses HAV, HEV. In the structure of morbidity, hepatitis A (Botkin’s disease) accounts for up to 1/3 of all cases of infection of pregnant women. Hepatitis E is an endemic disease detected mainly in developing Asian countries (India, Burma, etc.). Such viral liver lesions are not transmitted from mother to fetus.
- Hepatitis with hemocontact infection. Injection, sexual, vertical method of infection is characteristic of infections caused by HBV, HCV, HDV viruses. Diseases of this group can occur both acutely and chronically, causing gross destructive changes in liver tissue. When managing a pregnant woman, it is important to take into account the possibility of infection of the fetus and, if possible, perform prevention (administration of a vaccine, etc.).
In the classic acute course, infected with strains of HAV, HBV, HDV, HEV viruses after the incubation period, signs of intoxication syndrome with hyperthermia, arthralgia, weakness, fatigue, fatigue, sleep disorders occur. Possible dyspeptic phenomena in the form of nausea, decreased or lack of appetite, less often — vomiting. There is heaviness, swelling in the right hypochondrium, epigastric region. In 20-30% of pregnant women, similar sensations are noted in the left hypochondrium due to an enlarged spleen. A few days after the appearance of prodromal symptoms, the urine turns brown or brown, feces discolor, the color and consistency of which resemble white (gray) clay. The duration of the post-jaundice period ranges from 3-10 days to 1 month, depending on the characteristics of the pathogen, in some cases this period is absent.
The onset of the jaundice period, usually lasting from 1 to 3 weeks, is indicated by yellow staining of the skin and visible mucous membranes. At the same time, pregnant women suffering from hepatitis A have an improvement in general well-being. With hepatitis E, B, D, intoxication may increase. The formation of cholestasis is accompanied by the appearance of itching. The duration of the recovery period for different types of viral liver damage ranges from several months to a year. It is possible to have an erased and non-jaundiced course of the disease with minimal symptoms and rapid recovery.
In women with hepatitis C, a vivid clinical picture is usually absent, sometimes the infection becomes an accidental finding during laboratory screening. In most cases, the disease immediately becomes chronic with periodic deterioration of liver tests and the gradual development of extrahepatic autoimmune disorders (damage to the thyroid gland, kidneys, blood vessels, joints, bone marrow, etc.).
Pregnancy, as a rule, complicates the course of hepatitis, especially caused by the HEV virus. The aggravation of symptoms with the development of cholestasis is more pronounced after the 20th week of gestational age. In pregnant women who become ill in the 3rd trimester, viral hepatitis E can occur fulminantly with the occurrence of acute liver failure, progressive renal failure, DIC syndrome, premature birth, antenatal fetal death, stillbirth, developmental delays and severe hypoxia of newborns. With a fulminant course, maternal mortality reaches 20-50%.
Toxic dystrophy, submassive and massive liver necrosis with functional insufficiency, severe encephalopathy, hemorrhagic syndrome can complicate the course of acute hepatitis B and lead to the death of a woman. The mortality rate of pregnant women with this disease is 3 times higher than that of non-pregnant women. Chronization of the process with an increase in autoimmune disorders is noted in 10-15% of patients with hepatitis B, 80% with hepatitis C, 50% with hepatitis D. Long-term consequences in the form of fibrosis, cirrhosis of the liver, malignancy with the formation of primary hepatocellular carcinomas are characteristic of the chronic course of the disease.
Obstetric complications are usually observed in severe acute parenteral hepatitis and rarely in Botkin’s disease. In such patients, the course of gestosis is 1.6 times more likely to worsen, labor begins prematurely, premature discharge of amniotic fluid is noted, preeclampsia in childbirth is possible, the child is born in a state of hypoxia with poor indicators on the Apgar scale. According to the observations of obstetricians and gynecologists, the causative agents of all viral liver lesions are not teratogenic. Pathogens of hepatitis B, C, less often — D can be transmitted from the mother to the fetus through the placenta, during childbirth, while breastfeeding. The risk of infection ranges from isolated cases of infection with hepatitis D and 7-8% with hepatitis C to 80% with hepatitis B. The indicators are even higher for pregnant women suffering from immunodeficiency (HIV infection, etc.).
In the presence of epidemiological prerequisites and classical symptoms, diagnosis is not particularly difficult. Diagnostic difficulties are possible with atypical low-symptom course, reactivation of the chronic process. Taking into account the high risk of infection of the fetus with viral transmission and chronic course of hemocontact hepatitis, laboratory screening is carried out for all pregnant women. The examination plan usually includes methods aimed at detecting the virus and signs of liver dysfunction:
- Analyses for the verification of the pathogen. Specific ELISA markers of disorders are the corresponding total antibodies Ig (M+G), antibodies to non-structural proteins (in hepatitis C). DNA and RNA of viruses can be detected using PCR diagnostics. The REEF allows you to detect virus particles in liver tissue and other biological materials. In chronic hepatitis B and carrier, HBsAg is determined.
- Liver tests. A key marker of hepatocyte cytolysis is a minimum 10-fold increase in ALT activity. The indicator begins to increase from the end of the prodrome, reaches its maximum value during the peak period and gradually decreases to normal during convalescence. An increase in the concentration of alkaline phosphatase and gamma-glutamyltransferase indicates cholestasis.
- The study of protein metabolism. With an inflammatory lesion of the liver parenchyma, the indicators of the sulem test decrease, and the thymol test increase. The severity of the changes directly correlates with the severity of the infectious process. The level of total protein, albumin, is reduced. Dysproteinemia is noted. Due to the violation of protein synthesis in the liver, the indicators of the hemostasis system deteriorate.
- The study of pigment and lipid metabolism. Functional liver failure is manifested by hyperbilirubinemia with a predominant increase in the concentration of direct bilirubin, the presence of bile pigments and urobilinogen in the urine. Violation of cholesterol synthesis by hepatocytes damaged in acute and chronic forms of viral hepatitis in pregnancy is accompanied by a drop in its level in the blood.
In the general blood test, the number of leukocytes and neutrophils is reduced, the relative content of monocytes and lymphocytes is increased, ESR is often within the normal range, but can reach 23 mm /h. Ultrasound of the liver usually reveals an increase in the size of the organ, with different variants of the course, hypo-echogenicity, hyperechogenicity, heterogeneity of the structure are possible. Differential diagnosis is carried out between different variants of hepatitis. The infectious viral process also needs to be differentiated with damage to the hepatic parenchyma in benign lymphoblastosis, yersiniosis, leptospirosis, Far Eastern scarlet fever, medicinal hepatitis, severe early toxicosis, cholestasis of pregnant women, preeclampsia, acute fatty hepatosis of pregnant women, HELLP syndrome. In addition to the infectious disease specialist, the patient is advised by a therapist, hepatologist, dermatologist, neurologist, toxicologist according to indications.
A woman with a confirmed diagnosis is hospitalized in an infectious diseases department with obstetric wards. Termination of gestation by abortion is possible only in the early stages during the period of convalescence. The pregnant woman is shown a gentle regime with a restriction of motor activity. The correction of the diet provides for the exclusion of alcohol, fatty, fried foods, the consumption of dietary meat (chickens, turkey, rabbit), low-fat boiled, baked, steamed fish, cereals, dairy products, fresh vegetables and fruits. It is recommended to increase the volume of liquid consumed to 2 liters / day or more. It is advisable to drink alkaline mineral waters. In the convalescent period, restriction of physical activity, a sparing diet is shown.
Special etiotropic treatment of parenteral variants of hepatitis during gestation is not carried out. Pregnant women with a severe course of the disease, severe intoxication, a significant violation of liver functions are recommended medications with pathogenetic and symptomatic effects. Taking into account the symptoms , the treatment regimen may include the following groups of drugs:
- Detoxification agents. Both colloidal and crystalloid infusion solutions are used to remove toxic metabolites. Their appointment makes it possible to stop intoxication syndrome, reduce the intensity of itching with cholestasis, improve rheological blood parameters.
- Hepatoprotectors. The use of phospholipids, herbal remedies, amino acids, multivitamin complexes is aimed at stabilizing cell membranes, protecting hepatocytes from necrosis, tissue regeneration, and improving biochemical parameters. They are usually prescribed for convalescence.
- Choleretics and cholekinetics. Choleretic drugs are indicated for the threat or occurrence of cholestasis. They can reduce the load on hepatocytes, facilitate the outflow of bile, eliminate its stagnation in the gallbladder, reduce the severity of mesenchymal-inflammatory changes in the liver.
With changes in the blood coagulation system, the treatment regimen is supplemented with drugs that affect hemostasis. Pregnant women with extremely severe fulminant course, increasing liver failure are transferred to the intensive care unit for intensive therapy. The recommended method of delivery is natural childbirth in a physiological period. Caesarean section is performed only in the presence of obstetric or extragenital indications (placenta previa, clinically and anatomically narrow pelvis, transverse fetal position, tight cord entanglement, preeclampsia).
Prognosis and prevention
With timely diagnosis of acute viral hepatitis in pregnancy and the correct choice of medical tactics, the outcome of pregnancy is usually favorable. The maternal mortality rate does not exceed 0.4%, the mortality is due to severe extragenital pathology. The prognosis becomes more serious when infected with the causative agent of viral hepatitis E in the 2nd half of pregnancy. In such cases, the risk of death of a pregnant woman reaches 50%, in almost all cases the fetus dies. Chronic variants of the disorder during gestation are activated extremely rarely. Preventive measures are aimed at preventing infection, including compliance with personal hygiene and food hygiene, especially when living and visiting epidemiologically dangerous regions, refusal of unprotected sex, frequent change of sexual partners, injecting drug use, thorough examination of donor materials, processing of medical instruments.
Resistant lifelong immunity is formed to viruses that cause hepatitis A, E, B. For preventive purposes, vaccination against hepatitis A, B and emergency immunization with immunoglobulins against HAV is possible outside of gestation. Pregnant women are prescribed vaccines and serums with caution after studying all possible indications and contraindications. Active-passive prevention of infection of newborns with hemocontact hepatitis reduces the risk of infection by 5-10%. With viremia over 200 thousand . IU / ml for women suffering from hepatitis B, antiviral treatment with nucleoside reverse transcriptase inhibitors is prescribed, followed by active and passive immunization of the newborn.