Hepatitis caused by herpes simplex viruses

The herpes simplex virus was isolated by W. Gruter in 1912. In 1921, B. Lipschutz discovered acidophilic inclusions in the nuclei of cells of affected tissues, which are considered pathognomonic signs of this infection.

The herpes simplex virus contains DNA, the virion has a diameter of 120 to 150 nm, and reproduces well in the tissues of the chicken embryo. In infected cells, the virus forms intranuclear inclusions and giant cells, and has a pronounced cytopathic effect. The virus persists for a long time at low temperatures (-70 ^o C), is inactivated at 50-52 ^o C after 30 minutes, is sensitive to ultraviolet and X-rays, but can persist for a long time, 10 years or more, in a dried state. When the virus is introduced into the cornea of the eye of a rabbit, guinea pig, or monkey, keratoconjunctivitis occurs, and when administered intracerebrally, encephalitis occurs.

Herpes simplex viruses are divided into two groups based on their antigenic properties and differences in DNA nucleotide sequences: HSV 1 (human herpes virus type 1, HHV 1) and HSV 2 (human herpes virus type 2, HHV2). The first group is associated with the most common forms of the disease - lesions of the facial skin and mucous membranes of the oral cavity. Viruses of the second group more often cause lesions of the genitals, as well as meningoencephalitis. Liver lesions can be caused by both HSV 1 and HSV 2. Infection with one type of HSV does not prevent the occurrence of infection caused by HSV of another type.

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Epidemiology of hepatitis caused by herpes simplex virus

The infection is widespread. Infection occurs in the first 3 years of a child's life. Children in the first six months of life do not get herpes simplex infection due to the presence of specific IgG antibodies received transplacentally from the mother. However, in the absence of immunity in the mother, in case of infection, children in the first months of life get especially sick - they develop generalized forms. 70-90% of 3-year-old children have a fairly high titer of virus-neutralizing antibodies against HSV 2. From the age of 5-7, the number of children with a high level of antibodies to HSV 2 increases.

The source of infection is sick people and virus carriers. Transmission occurs through contact, sexual contact and, apparently, airborne droplets. Infection occurs through kissing through saliva, as well as through toys and household items infected with the saliva of a sick person or virus carrier.

Transplacental transmission of infection is possible, but infection of the child most often occurs during passage through the birth canal.

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Pathogenesis of hepatitis caused by the herpes simplex virus

The pathogenesis of HSV hepatitis has not been studied to date in either immunocompromised or immunocompetent patients. There is reason to believe that in some cases, latent HSV infection is reactivated during cytostatic therapy. The possibility of a direct cytopathic effect of HSV 1 and HSV 2 on hepatocytes cannot be ruled out.

Pathomorphology

Morphological changes in HSV hepatitis have not been sufficiently studied. Two forms are distinguished: focal and diffuse, in which diffuse microabscesses are detected, occupying more than 50% of the parenchyma, and multiple hepatocytes with characteristic intranuclear vitreous inclusions and Cowdry bodies type A.

The etiology of liver damage is confirmed by the presence of characteristic inclusions in hepatocytes - Cowdry bodies type A, detection of HSV1/2 viral particles using electron microscopy, detection of HSV antigens in hepatocytes using immunohistochemical methods, as well as antibodies to HSV in liver tissue.

Neonatal hepatitis caused by the herpes simplex virus is often accompanied by massive liver necrosis.

Symptoms of Hepatitis Caused by the Herpes Simplex Virus

The spectrum of HSV expressions of the liver varies from mild and subclinical to severe and malignant forms of hepatitis. In this case, HSV-gene git always has an acute course. Chronic course of the disease is not observed.

HSV hepatitis can develop in both immunocompetent and immunocompromised patients. Predisposing factors, in addition to immune disorders, including those caused by organ transplantation, taking steroid hormones not associated with organ transplantation, include pregnancy, use of inhalation anesthetics, etc.

The incubation period for HSV hepatitis has not been precisely established. However, it is known that in adult patients who have received organ transplants, liver damage develops on average 18 days after transplantation. This is earlier than with cytomegalovirus hepatitis, which develops 30-40 days after a similar intervention,

The pre-icteric period is not expressed in all patients; in some cases, the disease manifests itself with the appearance of jaundice.

Jaundice period

In most patients, liver damage is combined with fever, nausea, vomiting, abdominal pain, leukopenia, thrombocytopenia, coagulopathy. In some cases, HSV-etiology hepatitis occurs in a fulminant form.

Often, fulminant hepatitis caused by HSV 1 or HSV 2 is observed in pregnant women. In addition to isolated HSV hepatitis, pregnant women may develop fatal generalized HSV 2 infection, which includes, in addition to fulminant hepatitis, fever, progressive pneumonia with respiratory failure, leukopenia, DIC syndrome, acute renal failure, infectious toxic shock. In this case, the etiologic diagnosis is confirmed by the isolation of HSV 2 from the contents of vesicles, hepatocytes and other autopsy material.

Among those not suffering from immunodeficiency conditions, the disease is more common in newborns, but can also occur in older children and adults. Both isolated hepatitis and liver damage as a result of generalization of herpes simplex with damage to many organs and systems are possible. In this case, patients have high fever, severe symptoms of intoxication, drowsiness, respiratory distress, dyspnea, cyanosis, vomiting, enlarged liver, spleen, jaundice, bleeding. In the blood serum, the activity of liver-cell enzymes is increased, the level of conjugated bilirubin is increased, the prothrombin index is reduced. Typical herpetic rashes are absent in most patients with isolated HSV 1/2 hepatitis.

In this case, hepatitis in newborns caused by HSV may be accompanied by massive liver necrosis and lead to death. In some cases of HSV hepatitis in newborns, the activity of liver cell enzymes reaches high values (ALT up to 1035 U/l, AST up to 3700 U/l). The condition of such patients is always severe.

Treatment of hepatitis caused by the herpes simplex virus

Since the vast majority of patients with herpetic liver disease are not accompanied by vesicular rashes on the skin and mucous membranes, the virus is not considered by doctors as a possible etiologic cause of hepatitis, antiviral therapy is not prescribed, and many patients die from acute liver failure. In the case of empirical administration of acyclovir to immunocompetent and immunocompromised patients, this does not happen.

In a number of cases of acute HSV 1/2 hepatitis, a positive effect is achieved by treatment with antiviral drugs, primarily acyclovir, the timely intravenous administration of which can lead to a rapid improvement in the patient's condition.

Summarizing the above on the problem of HSV hepatitis, it can be said that this pathology, although rare, has great clinical significance. At the same time, there has been no detailed and in-depth study of the prognostic factors of predisposition of certain categories of patients to the development of this disease.