Hepatitis E

Viral hepatitis E is an acute viral disease with a fecal-oral mechanism of transmission of the pathogen, characterized by a cyclic course and frequent development of acute hepatic encephalopathy in pregnant women.

The assumption of the existence of at least two viral hepatitis with a fecal-oral mechanism of transmission of the pathogen originated in the 1950s. When analyzing outbreaks of viral hepatitis associated with waterborne infection. After the discovery of the hepatitis A virus and the possibility of verification of this disease, it became apparent that in epidemic periods, along with hepatitis A, other mass diseases of hepatitis with a fecal-oral route of transmission of infection occur. This was confirmed in a number of studies conducted in India, Nepal, as well as in the Central Asian countries. Attention was drawn to the fact that hepatitis A was mainly inflicted on children, mostly pre-school age, and the incidence of other viral hepatitis with a fecal-oral transmission was mainly for adults and older children. Experimental studies on monkeys allowed to establish the nosological independence of the new viral hepatitis. A major contribution to the discovery and study of the hepatitis E virus was made by domestic researchers led by prof. M.S. Balayan. This disease was called viral hepatitis "neither A nor B" with the fecal-oral mechanism of infection, according to the WHO recommendation, it is classified as hepatitis E

ICD code -10

B17.2.

Epidemiology of hepatitis E

The source of infection is a sick person who carries a typical or atypical (anicteric, worn out) form of the disease. Chronic carriage of the virus is not documented. The virus is detected in the patient's blood 2 weeks after infection, and in feces - a week before the onset of the disease and during the first week of the disease. Viremia lasts about 2 weeks. HEV is also secreted from animals and birds, which can be HEV reservoirs for humans. There are data on the transmission of HEV in transfusion of blood from a donor with an asymptomatic form of the disease and viremia.

The main mechanism of transmission is fecal-oral; describes water outbreaks associated with the use of faeces contaminated drinking water. Seasonality coincides with the period of rise in the incidence of hepatitis A. In our country the seasonality of viral hepatitis E falls on the autumn-winter period, in Nepal - for the time of monsoon rains.

The disease affects mainly the adult population, and the bulk of the diseased are people aged 15 to 35 years. So. During the outbreak of hepatitis E water from Central Asia, 50.9% of patients were between the ages of 15 and 29 and only 28.6% were children. It can not be ruled out that a small incidence of this hepatitis in childhood is associated primarily with the subclinical nature of the disease in children.

Hepatitis E occurs with a high frequency against the background of a high level of immunity to the hepatitis A virus.

Hepatitis E is mainly registered in the regions of South-East Asia; India, Nepal, Pakistan and Central Asia. The disease is characterized by its epidemic nature, involving large groups of the population in the epidemiological process. Characteristic for this hepatitis is the frequent occurrence of severe and malignant forms in pregnant women. In the CIS countries, the virus of this hepatitis is also found in the European part and Transcaucasia, as evidenced by the detection of specific antibodies in serial-production y-globulins from these regions. At the same time, antibodies to hepatitis E virus in y-globulins produced in Siberia and the Far East are not detected.

Typical seasonality of the infection: the rise in morbidity is associated with the beginning or end of the rainy season in South-East Asia, and in Central Asia the peak incidence falls on autumn. Periodic morbidity increases in endemic regions are recorded every 7-8 years. There are described repeated cases of viral hepatitis E, which may be due to the antigenic heterogeneity of the virus. HEV can be transmitted to the fetus from the mother in the third trimester of pregnancy. In countries in Europe and North America, the incidence of viral hepatitis E is sporadic and is documented in individuals returning from endemic regions. It should be noted that in patients with chronic hepatitis (viral, autoimmune), donors, hemophilia patients and those who underwent kidney transplantation, the frequency of detection of anti-HEV IgG is high. Which confirms the hypothesis of the risk of parenteral transmission of the virus from donors.

[1], [2], [3], [4], [5], [6], [7], [8],

What causes hepatitis E?

The hepatitis E virus (HEV) has a spherical shape, a diameter of about 32 nm and is close in its properties to caliciviruses (the Caliciviridae family ). The genome of the virus is represented by a single-stranded RNA. The virus quickly disintegrates under the influence of chlorine-containing disinfectants. It is less stable in the environment than HAV.

The pathogenesis of hepatitis E

The pathogenesis of hepatitis E has not been studied enough. It is believed that NEV enters the body of a person with contaminated water or food. From the intestine through the portal vein, the hepatitis E virus enters the liver and is adsorbed on the hepatocyte membrane, penetrates the cytoplasm, where its replication occurs NEV does not have a cytopathic effect. Many believe that liver damage with hepatitis E is immune-mediated. After exiting from infected hepatic cells, the hepatitis E virus enters the blood and bile, then the virus is excreted from the intestine with feces. When modeling hepatitis E in animals (monkeys, pigs), data were obtained suggesting that HEV can replicate in the lymph nodes of the intestine.

Viral hepatitis E is characterized by severe course of the disease in the third trimester of pregnancy, but the causes of this phenomenon are unknown. At the heart of the severe course of the disease is massive necrosis of hepatocytes, the development of thrombohemorrhagic syndrome due to a sharp deficit of plasma factors of hemostasis, as well as hemolysis, leading to acute hepatic insufficiency. In these cases, cerebral edema and DIC syndrome can lead to death.

Pathomorphology

The pathomorphological picture of hepatitis E does not differ from that of other viral hepatitis. Focal necrosis is revealed by the twilight infiltration of Kupffer cells and leukocytes, the phenomena of cytoplasmic and lobular cholestasis, and with fulminant form, discharge necrosis with complete disturbance of the structure of the hepatic tissue is detected.

Symptoms of hepatitis E

Hepatitis E has an incubation period that is 15-40 days, an average of about 1 month.

There are icteric and jaundiced forms of the disease (ratio 1: 9).

For icteric forms, an acute cyclical, predominantly mild course of the disease is characteristic (60% of all cases). There are acute and gradual onset of the disease. The pre-zheltushny period is often short and is 2-5 days, the manifestations of dyspeptic syndrome predominate. Such symptoms of hepatitis E, as a short-term fever (bowl subfebrile) occurs in 10-20% of patients. Approximately in 20% of patients, hepatitis E begins with a change in the color of urine and the development of jaundice. The duration of icteric period ranges from several days to one month (an average of 2 weeks), possibly the development of a cholestatic form with prolonged jaundice, skin itching.

1% of patients with icteric forms of viral hepatitis E develop fulminant hepatitis. Severe course of viral hepatitis E is observed in pregnant women (especially in the third trimester), as well as in parturient women during the first week after childbirth. Precursors of such a course even in the pre-jaundiced period of the disease can be expressed symptoms of hepatitis E: intoxication, fever, dyspeptic syndrome, pain in the right upper quadrant. After the appearance of jaundice, the symptoms of hepatic encephalopathy quickly grow until the coma develops. In this case, marked hemolysis, hemoglobinuria, oligoanuria, as well as a pronounced hemorrhagic syndrome caused by a decrease in activity (up to 2-7% of normal parameters) of hemostatic factors entering the prothrombin complex (II, VII, X). With the development of hemorrhagic syndrome there are massive gastrointestinal, uterine and other bleedings, which often lead to death. Pregnancy in most cases ends in fetal death, miscarriage, premature birth. Of the live births, every second person dies within a month. In endemic regions, viral hepatitis E in pregnant women in 70% of cases occurs fulminantly. Mortality is more than 50%, especially in the III trimester of pregnancy.

Diagnosis of hepatitis E

When making a diagnosis, it is necessary to take into account a complex of epidemiological data and clinical symptoms in the pre-yolk and icteric period.

For the presence of viral hepatitis E may indicate:

• the assumption of a waterway of disease transmission:
• Visiting a country endemic for viral hepatitis E;
• clinical manifestations similar to those in viral hepatitis A;
• the detection of severe forms with symptoms of hepatic encephalopathy, especially in pregnant women in the second half of pregnancy, the early postpartum period, or in nursing mothers.

Diagnosis of hepatitis E is to detect anti-HEV IgM in the blood serum, which appear in the blood 3-4 weeks after infection and disappear after a few months.

The results of serological tests for markers of viral hepatitis A, B and C are crucial. In the absence of antibodies to the hepatitis A virus (anti-HAV IgM), hepatitis B (HBsAg anti-HBcore IgM) markers, hepatitis C virus (anti -HV) and in the absence of parenteral history (in the next 6 months before the present disease), the assumption of hepatitis E.

The most accurate etiologic diagnosis of this disease is based on the detection of viral particles with the help of immune electron microscopy in fecal samples. Viral particles can be detected in feces, starting from the last week of the incubation period and up to the 12th day from the onset of the clinical manifestation of the disease. However, there is also a serological diagnosis of hepatitis E by detecting specific antibodies (anti-HEV and IgG) in the serum by ELISA. If necessary, the serum determination of RNA HEV is used by PCR.

Detection of different HEV infection markers has expanded the modern diagnostic capabilities. Depending on the detection of certain markers in the blood serum, one can judge the presence or transferred hepatitis E.

Specific markers of infection with hepatitis E virus and interpretation of their detection (Mikhailov MI et al., 2007)

Marker of infection with hepatitis E virus	Interpretation of the results of detection of markers of viral hepatitis E
IgM anti-HEV	Acute hepatitis E
IgG anti-HEV (total antibodies against HEU)	Postponed hepatitis E, protected against hepatitis E
IgA anti-HEV	Postponed hepatitis E
The NEV antigen	Virus replication
RNA NEV	Virus replication

[9], [10], [11], [12],

Differential diagnosis of hepatitis E

Differential diagnosis of hepatitis E is carried out between viral hepatitis E and other viral hepatitis, as well as acute fatty hepatosis (in pregnant women). In contrast to acute fatty hepatosis, viral hepatitis E is characterized by a significant (more than 20 norms) increase in ALT and ACT activity. In acute fatty hepatosis, almost normal transaminase activity is noted, a low level of total protein with a negative test result for anti-HEV IgM.

[13], [14], [15],

Treatment of hepatitis E

Etiotropic treatment of hepatitis E is absent.

When viral hepatitis E is used the same set of therapeutic measures as for other acute viral hepatitis of mild and moderate severity. In the case of severe disease, hepatitis E treatment is performed in intensive care units (wards) using all means and methods aimed at the prevention and treatment of hepatic encephalopathy, thrombohemorrhagic syndrome, including the use of corticosteroids. Protease inhibitors, oxygen therapy, detoxification therapy, cryoplasm, extracorporeal methods of detoxification.

Patients are discharged from the hospital after normalization of clinical and biochemical indicators with subsequent dispensary follow-up after 1-3 months after discharge.

How to prevent hepatitis E?

Specific prevention of hepatitis E

The vaccine against viral hepatitis E is undergoing clinical trials. In pregnant women living in endemic areas, it is advisable to use a specific immunoglobulin for preventive purposes.

Nonspecific prevention of hepatitis E

Measures to improve the water supply of the population, carry out hygiene measures to reduce the incidence of viral hepatitis A are effective against viral hepatitis E. Hepatitis E can be prevented if we carry out public health education aimed at explaining the dangers of using water from open water bodies (canals, irrigation canals , rivers) for drinking, washing vegetables without heat treatment, etc.