Hepatitis E

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

The existence of at least two viral hepatitises with the fecal-oral mechanism of transmission of the pathogen was suggested in the 1950s during the analysis of outbreaks of viral hepatitis associated with waterborne infection. After the discovery of the hepatitis A virus and the possibility of verifying this disease, it became obvious that during epidemic periods, along with hepatitis A, other mass hepatitis diseases with the fecal-oral route of transmission occur. This was confirmed in a number of studies conducted in India, Nepal, and Central Asian countries. Attention was drawn to the fact that hepatitis A mainly affects children, mainly preschoolers, and the incidence of other viral hepatitis with the fecal-oral route of transmission occurred mainly in adults and older children. Experimental studies on monkeys made it possible 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 Russian researchers led by prof. M.S. Balayan. This disease is called viral hepatitis "non-A, non-B" with a fecal-oral mechanism of infection, according to the WHO recommendation it is classified as hepatitis E

ICD-10 code

B17.2.

Epidemiology of hepatitis E

The source of infection is a sick person carrying a typical or atypical (anicteric, latent) form of the disease. Chronic carriage of the virus has not been recorded. 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 isolated from animals and birds, which can be HEV reservoirs for humans. There is evidence of HEV transmission during blood transfusion from a donor with an asymptomatic form of the disease and viremia.

The main transmission mechanism is feco-oral; waterborne outbreaks associated with drinking water contaminated with feces have been described. Seasonality is noted, coinciding with the period of increased incidence of hepatitis A. In our country, the seasonality of viral hepatitis E falls on the autumn-winter period, in Nepal - during the monsoon rains.

The disease mainly affects adults, and the majority of those infected are people aged 15 to 35 years. Thus, during the outbreak of hepatitis E in Central Asia, 50.9% of patients were aged 15 to 29 years, and only 28.6% were children. It cannot be ruled out that the low incidence of this hepatitis in childhood is mainly due to the subclinical nature of the disease in children.

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

Hepatitis E is registered mainly in the regions of South-East Asia; India, Nepal, Pakistan and Central Asia. The disease is characterized by an epidemic nature with the involvement of 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 the y-globulins of serial production from these regions. At the same time, antibodies to the hepatitis E virus are not detected in the y-globulins produced in Siberia and the Far East.

The infection is characterized by seasonality: the increase in incidence is associated with the beginning or end of the rainy season in Southeast Asia, and in Central Asian countries the peak incidence occurs in autumn. Periodic increases in incidence in endemic regions are recorded every 7-8 years. Repeated cases of viral hepatitis E have been described, 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 Europe and North America, the incidence of viral hepatitis E is sporadic and is recorded in individuals returning from endemic regions. It should be noted that patients with chronic hepatitis (viral, autoimmune), donors, patients with hemophilia and individuals who have undergone kidney transplantation have a high frequency of detection of anti-HEV IgG, which confirms the hypothesis of the risk of parenteral transmission of the virus from donors.

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What causes hepatitis E?

The hepatitis E virus (HEV) is spherical, about 32 nm in diameter, and is similar in properties to caliciviruses (family Caliciviridae). The virus genome is single-stranded RNA. The virus is quickly destroyed by chlorine-containing disinfectants. It is less stable in the environment than HAV.

Pathogenesis of hepatitis E

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

Viral hepatitis E is characterized by a severe course of the disease in the third trimester of pregnancy, but the causes of this phenomenon are unknown. The basis of the severe course of the disease is massive necrosis of hepatocytes, the development of thrombohemorrhagic syndrome due to a sharp deficiency of plasma hemostasis factors, as well as hemolysis, leading to acute liver failure. 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 with twilight infiltration of Kupffer cells and leukocytes, cytoplasmic and lobular cholestasis are detected, and in the fulminant form, confluent necrosis with complete disruption of the structure of the liver tissue is detected.

Symptoms of Hepatitis E

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

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

Icteric forms are characterized by an acute cyclic, predominantly mild course of the disease (60% of all cases). A distinction is made between acute and gradual onset of the disease. The pre-icteric period is often short and lasts 2-5 days, with manifestations of dyspeptic syndrome predominating. Symptoms of hepatitis E such as short-term fever (usually subfebrile) occur in 10-20% of patients. In approximately 20% of patients, hepatitis E begins with a change in urine color and the development of jaundice. The duration of the icteric period ranges from several days to one month (on average 2 weeks), and the development of a cholestatic form with prolonged jaundice and skin itching is possible.

In 1% of patients with icteric forms of viral hepatitis E, fulminant hepatitis develops. Severe course of viral hepatitis E is observed in pregnant women (especially in the third trimester), as well as in women in labor during the first week after childbirth. Harbingers of such a course even in the pre-icteric period of the disease may be pronounced symptoms of hepatitis E: intoxication, fever, dyspeptic syndrome, pain in the right hypochondrium. After the appearance of jaundice, symptoms of hepatic encephalopathy rapidly increase up to the development of coma. In this case, pronounced hemolysis, hemoglobinuria, oliguria, as well as a sharply expressed hemorrhagic syndrome are noted, caused by a decrease in the activity (up to 2-7% of normal values) of hemostasis factors included in the prothrombin complex (II, VII, X). With the development of hemorrhagic syndrome, massive gastrointestinal, uterine and other bleeding occurs, which often lead to death. Pregnancy in most cases ends with intrauterine death of the fetus, miscarriage, premature birth. Of those born alive, every second one dies within a month. In endemic regions, viral hepatitis E in pregnant women is fulminant in 70% of cases. Mortality is more than 50%, especially in the third trimester of pregnancy.

Diagnosis of hepatitis E

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

The presence of viral hepatitis E may be indicated by:

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

Diagnosis of hepatitis E involves the detection of anti-HEV IgM in the blood serum, which appears in the blood 3-4 weeks after infection and disappears after several months.

The results of serological studies for markers of viral hepatitis A, B and C are of decisive importance. In the absence of antibodies to the hepatitis A virus (anti-HAV IgM), markers of the hepatitis B virus (HBsAg anti-HBcore IgM), hepatitis C virus (anti-HCV) in the blood serum and in the absence of a parenteral history (in the next 6 months before the current disease), the assumption of hepatitis E will be justified.

The most accurate etiological diagnosis of this disease is based on the detection of viral particles using 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 clinical manifestation of the disease. However, there is also serological diagnosis of hepatitis E by detecting specific antibodies (anti-HEV and IgG) in the blood serum using the ELISA method. If necessary, the determination of HEV RNA in the blood serum using PCR is used.

The discovery of various markers of HEV infection has expanded modern diagnostic capabilities. Depending on the detection of certain markers in the blood serum, one can judge the presence or past hepatitis E.

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

Hepatitis E virus infection marker	Interpretation of the results of detection of markers of viral hepatitis E
IgM anti HEV	Acute hepatitis E
IgG anti-HEV (total antibodies against HEV)	Previous hepatitis E, protection against hepatitis E
IgA anti-HEV	Previous hepatitis E
HEV antigen	Virus replication
RNA HEV	Virus replication

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Differential diagnosis of hepatitis E

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

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Treatment of hepatitis E

There is no etiotropic treatment for hepatitis E.

In viral hepatitis E, the same complex of therapeutic measures is used as in other acute viral hepatitis of mild and moderate severity. In case of severe course of the disease, treatment of hepatitis E is carried out in intensive care units (wards) using all means and methods aimed at prevention and treatment of liver 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 parameters, followed by dispensary observation 1-3 months after discharge.

How to prevent hepatitis E?

Specific prevention of hepatitis E

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

Non-specific prophylaxis of hepatitis E

Measures to improve water supply to the population, implementation of hygienic measures to reduce the incidence of viral hepatitis A are also effective against viral hepatitis E. Hepatitis E can be prevented by conducting health education work among the population aimed at explaining the dangers of using water from open water bodies (canals, irrigation ditches, rivers) for drinking, washing vegetables without heat treatment, etc.