What is Cytomegalovirus Hepatitis?
Cytomegalovirus hepatitis is the leading clinical manifestation of congenital cytomegalovirus infection. Damage to the liver with cytomegalovirus infection is always a sign of a generalized process.
Causes of Cytomegalovirus Hepatitis
The causative agent of cytomegalovirus infection is the DNA genomic virus of the genus Cytomegalovirus (Cytomegalovirus hominis) of the subfamily Vetherpesvirinae of the family Herpesviridae. There are 3 known strains of the virus: Davis, AD-169 and Kerr. Slow reproduction of the virus in the cell is possible without damaging it. The virus is inactivated by heating and freezing, is well preserved at room temperature. At – 90 ° C, it remains for a long time, is relatively stable at pH 5.0–9.0 and rapidly decomposes at pH 3.0.
The reservoir and source of infection is a person with an acute or latent form of the disease. The virus can be in various biological secrets: saliva, nasopharynx, tears, urine, bowel movements, seminal fluid, cervical secretions.
The transmission mechanisms are diverse, the transmission methods are airborne, contact (direct and indirect through household items) and transplacental. Possible infection through sexual contact, during transplantation of internal organs (kidney or heart) and blood transfusion of an infected donor. Intranatal infection of the child is observed much more often than transplacental. The most dangerous for the fetus infection of the mother in the first trimester of pregnancy. In such situations, the highest frequency of intrauterine developmental disorders.
The natural susceptibility of people is high, but latent infection is widespread. Clinical manifestations of infections attributable to opportunistic diseases are possible in conditions of primary or secondary immunodeficiency.
The main epidemiological signs of cytomegalovirus infection. The disease is registered everywhere, antiviral antibodies detected in 50-80% of adults testify to its widespread distribution. The variety of CMV infections and the polymorphism of the clinical picture determine the epidemiological and social significance of CMV infection. This disease plays an important role in transplantology, blood transfusion, perinatal pathology, can be the cause of prematurity, stillbirths, congenital defects of development. In adults, CMV infection is seen as a concomitant disease in various immunodeficiency states. Ongoing environmental pollution, the use of cytostatics and immunosuppressants contribute to an increase in the frequency of CMV infection. In recent years, its exacerbation in HIV-infected people has become especially relevant. In pregnant women with latent CMV infection, fetal damage does not always occur. The probability of intrauterine infection is significantly higher during the initial infection of a woman during pregnancy. No seasonal or occupational morbidity features have been identified.
Pathogenesis during Cytomegalovirus Hepatitis
For various transmission routes, the mucous membranes of the upper respiratory tract, gastrointestinal tract or genitals can be the gates of infection. The virus enters the blood; short-term viremia quickly ends with the localization of the pathogen when introduced into white blood cells and mononuclear phagocytes, where it is replicated. Infected cells increase in size (cytomegaly), acquire a typical morphology with nuclear inclusions, which are accumulations of the virus. The formation of cytomegal cells is accompanied by interstitial lymphohistiocytic infiltration, the development of nodular infiltrates, calcifications and fibrosis in various organs, glandular structures in the brain.
The virus is able to persistently and latently persist in organs rich in lymphoid tissue, being protected from the effects of antibodies and interferon. At the same time, it can suppress cellular immunity by a direct effect on T-lymphocytes. In various immunodeficiency states (in early childhood, during pregnancy, the use of cytostatics and immunosuppressants, HIV infection) and, above all, with cellular immunity disorders, further aggravated by direct exposure to the virus, pathogen reactivation and hematogenous generalization with damage to almost all organs and systems are possible . In this case, the epitheliality of the virus is of great importance. It is especially pronounced in relation to the salivary gland epithelium, which, under the influence of the virus, turns into cytomegal cells.
A special place in CMVI is liver pathology. Cytomegalovirus hepatitis, which develops in response to the introduction of CMV, is characterized by degeneration of the epithelium of the biliary tract and hepatocytes, stellate endotheliocytes and vascular endothelium. They form cytomegal cells, inflammatory mononuclear infiltrates are located in their environment. The combination of these changes leads to intrahepatic cholestasis. Cytomegalic cells are desquamated, fill the gaps of the bile ducts, causing the mechanical component of jaundice. At the same time, degenerated CMV hepatocytes are destructively changed up to necrosis, causing the development of cytolysis syndrome. It should be noted that with CMV hepatitis, which has a prolonged, subacute or chronic course, the leading role belongs to cholestasis syndrome.
Symptoms of Cytomegalovirus Hepatitis
Cytomegalovirus hepatitis can occur in anicteric and icteric form.
An anicteric form of CMV hepatitis occurs with very poor clinical symptoms, the condition of the children remains satisfactory. Identification of an anicteric form of hepatitis is possible in connection with the detection of hepatomegaly and elevated levels of aminotransferases. The activity of aminotransferases increases slightly (1.5-2.0 times) with the predominance of AcAT over AlAT.
In the icteric form of hepatitis, two groups of patients are distinguished: one with a favorable course and gradual recovery and the other group with progressive liver disease and the formation of biliary cirrhosis due to the development of obliterating cholangitis.
The condition of children with an icteric form of CMV hepatitis is not significantly impaired. They have hepatosplenomegaly. Most children had jaundice in the first days after birth.
The icteric form of CMV hepatitis with a favorable course is characterized by mild jaundice of the skin, dark urine and colored feces, hepatosplenomegaly, moderate hyperfermentemia with a predominance of AcAT over ALAT, an increase in bilirubin with a predominance of direct fraction, and the presence of markers of active replication of CMV.
One of the variants of cytomegalovirus liver damage in congenital CMVI is the formation of biliary cirrhosis, which leads to death, as a rule, in the second half of the first year of life.
Children born with cytomegalovirus hepatitis have low Apgar scores (a scale that reflects the state of the baby’s nervous system at the time of birth), insufficient muscle development, and increased or decreased muscle tone. There may be short-term muscle twitches or cramps, the baby does not take the chest, all congenital reflexes are reduced. In general, the condition of such a child will be severe, hemorrhagic syndrome (nosebleeds, gastrointestinal bleeding, hemorrhagic rash on the skin and mucous membranes) will be severe, the number of red blood cells and platelets in the blood will decrease, and the central nervous system will be affected. Yellowness of the skin, mucous membranes and sclera appears on the first day or two, gradually increasing, it lasts 1-2 months. On examination, the liver is enlarged, the spleen is also enlarged. The respiratory system is often involved, children cough, there is shortness of breath. Soon, signs of hydrocephalus or microcephaly, oligophrenia, damage to the optic nerves, kidneys, stomach, and intestines can be detected. In the blood, hepatocellular enzymes will be sharply increased, the protein and albumin fraction of the protein will be reduced. This process often ends fatally. With a benign course, jaundice remains 2-3 months, after which it begins to subside.
Diagnosis of Cytomegalovirus Hepatitis
The diagnosis of cytomegalovirus hepatitis was established on the basis of anamnestic, clinical and biochemical data with mandatory confirmation of the diagnosis by the detection of markers of CMVI. Markers of parenteral viral hepatitis were examined in all patients.
In the diagnosis of cytomegalovirus hepatitis, the results of a liver puncture biopsy are of great importance (detection of punctate giant cells with a diameter of 25-40 microns in the form of an owl eye with a huge nucleus and narrow border of cytoplasm), as well as the cytological method (detection of cytomegalic cells in urine sediment) and serological method (detection of antibodies – Ig M to CMVI). Differential diagnosis of CMV hepatitis is carried out with other viral hepatitis: B, Epstein-Barr, herpetic hepatitis.
In the biochemical analysis of blood, a distinct hyperfermentemia is revealed with the predominance of AcAT (160.0 ± 25.6 μmol / min.L) over AlAT (120.0 ± 25.6 μmol / min.L) and hyperbilirubinemia (112.0 ± 8.5 μmol / L) with a predominance of the direct fraction (62.0 ± 6.7 μmol / L).