Cytomegalovirus hepatitis in children. What is CMV hepatitis and its forms. Congenital hepatitis CMV type

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As a manuscript.

IVANOVA YULIA NIKOLAEVNA

dissertations for an academic degree

candidate of medical sciences

Moscow – 2010

The work was carried out at the State educational institution higher professional education "Russian State Medical University Federal agency on Health and Social Development"

Scientific director:

Doctor of Medical Sciences,
Professor Smirnov Andrey Viktorovich

Official opponents:

Doctor of Medical Sciences,
Professor Filin Vyacheslav Alexandrovich

Doctor of Medical Sciences,
Professor Bokovoy Alexander Grigorievich

Leading organization:

Research Institute of Virology named after. DI. Ivanovsky RAMS.

The defense will take place on October 11, 2010 at 14.00 at a meeting of the dissertation council D 208.072.02 at the State Educational Institution of Higher Professional Education of the Russian State Medical University of Roszdrav at the address: 117997, Moscow, st. Ostrovityanova, 1.

The dissertation can be found in the library of the State Educational Institution of Higher Professional Education of the Russian State Medical University of Roszdrav at the address: 117997, Moscow, st. Ostrovityanova, 1

Scientific secretary of the dissertation council
Doctor of Medical Sciences, Professor N.P. Kotlukova

GENERAL DESCRIPTION OF WORK

The relevance of research.

Liver lesions continue to occupy a significant place in the structure of diseases of the digestive system. There is no doubt that one of the leading causes of liver damage in children and adults is infectious agents. The introduction of modern methods for diagnosing infectious diseases into clinical practice has shown that the etiological structure infectious lesions liver is not limited to hepatitis viruses A, B, C, D, E, G, TTV. Currently accumulated data from clinical, morphological, biochemical and virological studies indicate the participation of cytomegalovirus in the development of acute and chronic hepatitis. Liver damage can form as a result of congenital and acquired cytomegalovirus infection, having both an acute and chronic course. However, many epidemiological, clinical, immunopathogenetic aspects of cytomegalovirus liver damage still remain unstudied. Currently, there is no unified approach to the classification of cytomegalovirus hepatitis, there is no data on the frequency of certain clinical forms of the disease, the clinical manifestations and features of the course have not been studied, and diagnostic criteria for various forms of cytomegalovirus hepatitis have not been developed. This hinders the development of uniform recommendations for the management of this category of patients. Insufficient knowledge of this disease and its untimely diagnosis lead to a worsening prognosis for the patient, preventing the appointment of adequate and timely therapy.

Thus, at present, research devoted to the study of clinical and laboratory manifestations of various clinical forms of cytomegalovirus hepatitis and the characteristics of the course of this disease, the development of diagnostic criteria for differentiated approach to the treatment and follow-up of patients with this pathology.

Purpose of the study:

to study clinical and laboratory manifestations and features of the course of cytomegalovirus hepatitis in children.

Research objectives:

To study clinical and laboratory manifestations and outcomes of acute acquired cytomegalovirus hepatitis in children.
To study clinical and laboratory manifestations and features of the course of chronic acquired cytomegalovirus hepatitis in children.
To study clinical and laboratory manifestations and features of the course of congenital chronic cytomegalovirus hepatitis in children without biliary tract malformations.
To study clinical and laboratory manifestations and features of the course of congenital chronic cytomegalovirus hepatitis in children with biliary tract malformations.

Scientific novelty.

It has been established that cytomegalovirus in some cases can cause acute and chronic hepatitis, both acquired and congenital, which is combined in some children with malformations of the biliary tract.

The hepatotropic nature of cytomegalovirus is confirmed by the detection of CMV DNA in hepatocytes of patients by polymerase chain reaction and cytomegalovirus late antigen (CMV-LA) by immunohistochemistry using monoclonal antibodies (clone QB1/06).

For the first time, clinical and laboratory manifestations of acute acquired cytomegalovirus hepatitis, chronic acquired and congenital cytomegalovirus hepatitis in children with and without malformations of the biliary tract are described in detail.

For the first time, the features of the course and outcomes of various forms of cytomegalovirus hepatitis in children have been studied.

Practical significance.

Variants of the course of cytomegalovirus hepatitis in children have been identified, their clinical manifestations, features of the course and outcomes have been studied.

The necessary set of examinations of children with acute and chronic cytomegalovirus hepatitis has been determined.

A tactic has been developed for the joint management of pediatricians, infectious disease specialists and surgeons for patients with congenital cytomegalovirus hepatitis combined with biliary tract malformations.

Provisions submitted for defense.

Cytomegalovirus is capable of exerting a hepatotropic effect, leading in some cases to the formation of acute and chronic hepatitis in children.

Cytomegalovirus hepatitis can be either acquired or congenital in nature, accompanied in some patients by malformations of the biliary tract.

Clinical and laboratory manifestations of cytomegalovirus hepatitis in children are not fundamentally different from those with viral hepatitis of other etiologies.

Implementation of research results.

The results of the dissertation were introduced into the practice of the State Institution of the Russian Children's Clinical Hospital of Roszdrav (RDCH), Children's City Clinical Hospital No. 9 named after. G.N. Speransky, Moscow. The main provisions of the work are used when carrying out training sessions and giving lectures at the Department of Infectious Diseases in Children of the Pediatric Faculty of the State Educational Institution of Higher Professional Education RGMU, the Department of Infectious Diseases in Children of the Moscow Faculty of the State Educational Institution of Higher Professional Education RGMU, and are also included in teaching aids for students, interns, residents and doctors.

Approbation.

The dissertation materials were presented at the joint scientific and practical conference of employees of the Department of Infectious Diseases in Children of the Pediatric Faculty of the State Educational Institution of Higher Professional Education RGMU, the Department of Infectious Diseases in Children of the Moscow Faculty of the State Educational Institution of Higher Professional Education RGMU of the Russian Children's Clinical Hospital of Roszdrav, Infectious Diseases Section of the Moscow City Branch of the Union of Pediatricians of Russia, 2006 ., VI Congress of Children's Infectious Diseases of Russia (Moscow, 2007), VII Congress of Children's Infectious Diseases of Russia (Moscow, 2008), VIII Congress of Children's Infectious Diseases of Russia (Moscow, 2009).

Publications.

Scope and structure of work.

The dissertation consists of an introduction, a literature review, 5 chapters of own research, a conclusion and a literature index, including 121 domestic and 228 foreign sources. The dissertation is presented on 179 pages of typewritten text, contains 9 extracts from the medical history, 22 tables and 28 figures.

MATERIALS AND METHODS OF RESEARCH.

The work was carried out at the Department of Infectious Diseases in Children, Faculty of Pediatrics, State Educational Institution of Higher Professional Education, Russian State Medical University, Federal Agency for Health and Social Development (head of the department - Academician of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences V.F. Uchaikin) in 2004-2008. Clinical observation of patients was carried out on the basis of the State Institution of the Russian Children's Clinical Hospital (RDCH) of the Federal Agency for Health and Social Development - chief physician professor, doctor of medical sciences N.N. Vaganov.

In total, we observed 114 children with cytomegalovirus hepatitis aged 1 month and older. up to 16 years old. Of these, 94 (82.5%) children were under the age of 1 year, 9 (7.9%) children were from 1 to 3 years old, 4 (3.5%) children were from 3 to 7 years old, and over 7 years old – 7 (6.1%) children. Among the patients with cytomegalovirus hepatitis, there were 55 (48.2%) boys and 59 (51.8%) girls.

When analyzing clinical data, we used the classification of viral hepatitis in children proposed by N.I. Nisevich (1999). The diagnosis of the disease was established on the basis of clinical and epidemiological data, the results of a biochemical examination, ultrasound scanning liver. When making a diagnosis, modern methods of serological and virological diagnosis of viral hepatitis were used.

Congenital cytomegalovirus infection was diagnosed when markers of cytomegalovirus infection were detected in patients (anti-CMV Ig M and anti-CMV Ig G, CMV DNA in the blood) immediately after birth or in the first month of the child’s life and when markers of cytomegalovirus infection were detected in the mother.

The acquired nature of cytomegalovirus infection was evidenced by the detection of markers of cytomegalovirus infection (anti-CMV Ig M and anti-CMV Ig G, CMV DNA in the blood) from the end of the first month of the child’s life in the absence of markers of cytomegalovirus infection in the mother (Uchaikin V.F., 1998 .).

The diagnosis of acute cytomegalovirus hepatitis was established when markers of the acute phase of cytomegalovirus infection (anti-CMV Ig M, CMV DNA) were detected in patients with a clinical picture of acute viral hepatitis in the absence of acute phase markers herpetic infections Type I, II, VI, Epstein-Barr viral infection, viral hepatitis A, B, C, D, G, TTV, enterovirus infection and toxoplasmosis.

Chronic cytomegalovirus hepatitis was diagnosed in the presence of clinical and laboratory symptoms of hepatitis lasting more than 6 months, detection of antibodies to cytomegalovirus (anti-CMV Ig M and anti-CMV Ig G) in the blood serum, detection of CMV DNA in the blood and liver tissue using the polymerase chain reaction method , detection of CMV late antigen (CMV-LA) in liver tissue by immunohistochemistry using monoclonal antibodies (clone QB1/06) and in the absence of markers of herpetic infections types I, II, VI, Epstein-Barr virus, viral hepatitis A, B, C , D, G, TTV, enterovirus infection and toxoplasmosis, as well as with the exclusion of all other causes that can lead to chronic liver damage (congenital pathology of the liver and spleen vessels, alpha-1-antitrypsin deficiency, Wilson-Konovalov disease, etc.) (Uchaikin V.F., 1998).

Currently, the classification of chronic hepatitis is generally accepted (Desmet V. et. al., 1995), which is based on the morphological signs of chronic hepatitis. The severity of the condition, the early age of the patients we examined, as well as the high risk of a number of serious complications did not allow us to perform a puncture biopsy of the liver, and, consequently, to carry out a morphological study of the liver tissue in all patients. In this regard, taking into account the clinical experience of the department, we developed criteria (Uchaikin V.F. et al., 2000), on the basis of which we diagnosed various forms of chronic cytomegalovirus hepatitis. Aminotransferase activity was used as an indicative criterion for the degree of activity of chronic hepatitis. The level of other serum enzymes (alkaline phosphatase, gammaglutamyl transpeptidase), as well as albumin and prothrombin index in chronic hepatitis are usually mildly changed and significantly worsen in liver cirrhosis. Therefore, these tests were not used to assess the degree of activity of chronic hepatitis as they were not informative enough (Uchaikin V.F. et al., 2000).

The stages of chronic hepatitis reflect its dynamics, tendencies towards regression or progression. Histological assessment of the stages of chronic hepatitis is based on the severity of fibrosis (Uchaikin V.F. et al., 2000).

There are 5 stages of chronic hepatitis or variants of fibrosis:

1. No fibrosis;

2. Mild fibrosis;

3. Moderate fibrosis;

4. Severe fibrosis;

5. Cirrhosis.

The results of ultrasound scanning of the liver were used to assess the degree of fibrosis. We used the following ultrasound criteria for the stages of fibrosis in chronic hepatitis, obtained at our department (Table 1).

Table 1. Ultrasound criteria for stages of liver fibrosis

for chronic hepatitis in children

DEGREE OF FIBROSIS	ULTRASONIC SIGNS
No fibrosis	The liver is not enlarged. The contour of the liver is smooth. The parenchyma is homogeneous (homogeneous) in all sections, low echogenicity. Vessels gate system not expanded.
Mild (mild) fibrosis	The liver is slightly enlarged. The contour of the liver is smooth. The parenchyma is homogeneous, evenly or only in the periportal zone, weakly compacted due to small focal structures gray(height of reflected signals up to 1/3 of maximum). The vessels of the portal system are not dilated.
Moderate fibrosis	The liver is enlarged. The contour of the liver is smooth. The parenchyma is compacted evenly or in patches due to small-focal, heterogeneous structures of light gray and white color (the height of the reflected signals is up to 1/2 of the maximum). The vessels of the portal system, as a rule, are not dilated. IN lower parts a weakening of the ultrasound signal is noted.
Severe (pronounced) fibrosis	The liver is slightly enlarged due to the right lobe. The contour of the liver is smooth. The parenchyma is evenly compacted due to small focal structures high density with a predominance of white color (the height of reflected signals is up to 2/3 of the maximum). Thin interlobar septa, thickening and compaction of the capsule are revealed. The vessels of the portal system are somewhat dilated, with a perivascular reaction. In the lower sections there is a moderate weakening of ultrasound signals.
Cirrhosis	The liver is slightly enlarged due to the right lobe. The contour of the liver is often uneven. The capsule is dense. The parenchyma is evenly compacted in all parts of the liver due to small-, medium-, and/or large-focal structures, mostly white (the height of the reflected signals is from 2/3 to a maximum). In the lower lobes the ultrasonic signal is sharply weakened. Thick and dense interlobar septa are identified. Medium-sized bile ducts are poorly visualized. The vessels of the portal and splenic veins are dilated, tortuous, collaterals are visible, often multiple (angiomatous transformation). In the stage of hepatic cell failure - ascites.

State Institution "Samara Regional Bureau of Forensic Medicine".

Head of the Bureau - Doctor of Medical Sciences, Professor, Head of the Department of Forensic Medicine, Samara State Medical University, Roszdrav

Ardashkin Anatoly Panteleevich.

1. Filippenkova Elena Igorevna, doctor - forensic expert of the histological department of the Samara Regional Bureau of Forensic Medicine, expert work experience 10 years, 1 qualification category.

Glass preparations were provided by the Department of Forensic Medicine of the Izhevsk State Medical Academy.

CYTOMEGALOVIRUS INFECTION.

Cytomegalovirus infection in the internal medicine clinic

V. V. Skvortsov, R. G. Myazin, D. N. Emelyanov

Volgograd State Medical University, Volgograd

One of the leading places among diseases caused by viruses of the family Herpesviridae, is occupied by cytomegalovirus infection (CMVI), an increase in the prevalence of which is currently observed in all countries of the world. Over the past decade, the list of diseases, one of the causes of which is also cytomegalovirus (CMV), has expanded significantly. The concept of CMV infection covers the problems of intrauterine infection, seronegative mononucleosis, hepatitis, diseases gastrointestinal tract, post-transfusion syndrome, organ and tissue transplantation, oncogenesis, HIV infection, since CMV infection is defined by WHO experts as AIDS-defining disease. The most successful definition of this disease seems to be: “Cytomegalovirus infection is a widespread viral disease predominantly in young children, characterized by a wide variety of clinical manifestations and a standard two-component morphological picture, including peculiar owl-eye-like cytomegalic cells and lymphohistiocytic infiltrates.”

Etiology

CMV was first described in 1881 by the German pathologist M. Ribbert, who discovered cytomegalic cells (CMC) in kidney tissue in congenital syphilis. E. Goodpasture and F. Talbot in 1921 proposed the name “infantile cytomegaly,” which is still used today. CMV was isolated from cell culture by M. Smith in 1956.

The diameter of CMV virions is 120-150 nm. The virion is covered with a glycoproteinolipid envelope. The CMV virus has the shape of an ixahedron, the protein shell of which (capsid) consists of 162 symmetrically arranged capsomers. The CMV genome is represented by double-stranded DNA. CMV is thermolabile, inactivated at a temperature of +56°C, its optimal pH is 7.2-8.0. Currently, three strains of CMV have been isolated: Davis, AD 169, Kerr.

Epidemiology

Reservoir of CMV in nature is only human. The virus is released from an infected body urine, saliva and tear fluid. CMV transmission factors may be mother's blood, cervical and vaginal secretions, breast milk and sperm. The prevalence of CMV infection depends on the socio-economic and hygienic living conditions of people. Screening studies using enzyme-linked immunosorbent assay (ELISA) revealed antibodies to CMV in 33% of children under 2 years of age and in 50% of adults in countries with high level life. In developing countries, 69% of children and 100% of adults have specific antibodies.

The main source of infection of children are mothers who are carriers of CMV.. Intrauterine infection of the fetus can occur at any stage of antenatal development. Transplacental hematogenous infection of the fetus is facilitated by reactivation of CMV infection in pregnant women and insufficient barrier function of the placenta. The risk of infection penetrating the placental barrier increases with prolonged viremia and the chronic nature of the infection. In cervical secretions, CMV is detected in the first trimester of pregnancy in 2% of women, in the second - in 7%, in the third - in 12%. The fetus can aspirate amniotic fluid infected with CMV; damage to the external integument of the fetus can also serve as an entry point for CMV. 5% of newborns are infected intranatally. Infection of the fetus early stages intrauterine development poses the greatest danger and often accompanied by spontaneous abortion or disorders of organo- and histogenesis. In those infected with CMV, more late dates observed after birth cytomegaly syndrome, transient jaundice, hepatosplenomegaly. Subsequently, from 10 to 30% of such children suffer from brain damage, expressed in microcephaly with ventricular calcification, atrophy auditory nerve and mental retardation.

Infants may become infected through milk during natural feeding. However, with mother's milk the child receives secretory IgA, which does not penetrate the placenta and is not produced in the child in the first months of postnatal life. Secretory IgA increases the newborn's resistance to viral and bacterial infections, so children infected through mother's milk, suffer only latent form of CMV.

In case of close contact between mother and child, a factor in transmitting the virus to him or her can become saliva. There is evidence that half of children under 3 years of age attending kindergartens are infected with CMV from their peers and then infect their mothers.

The source of CMV for adults and children can be urine of a patient or virus carrier.

A common route of infection is sexual, since the virus is contained in sperm in high concentrations for a long time.

There is also airborne infection. In patients with a severe form of acute respiratory viral infection, which is often caused by CMV, cytomegalovirus is detected in nasopharyngeal swabs.

Blood transfusions, infusion therapy, organ and tissue transplantation are also dangerous, since they are often introduced into the recipient’s body biological drugs or tissue from CMV-infected donors. The use of immunosuppressants and cytostatics in patients after organ transplantation not only promotes the reactivation of previously acquired latent infection, but also increases their susceptibility to primary CMV infection.

The presence of antigenically different strains of CMV explains the possibility of reinfection with the development of the manifest form of the disease at any age.

Pathogenesis

CMV has pronounced tropism for the tissues of the salivary glands. In the latent form of the virus is discovered only in the epithelium of salivary tubes Therefore, sometimes CMV is rightly called the “kissing disease.”

CMV causes significant violations regulation of the immune response, which are based on damage to the interleukin system. As a rule, the ability of infected immunocompetent cells to synthesize interleukins is suppressed due to excessive production of prostaglandins, and the responses of target cells to IL-1 and IL-2 are also changed. Developing virus-induced immunosuppression with a sharp inhibition of natural killer cell function.

Penetrated into blood CMV reproduces in leukocytes and the mononuclear phagocyte system or persists in lymphoid organs. CMV virions are adsorbed on cell membranes, penetrate the cytoplasm and induce cytomegalic cell metamorphosis. Viral RNA found in T-helpers and T-suppressors even in long-term periods of convalescence.

Pathanatomy

The characteristic pathomorphological sign of CMV is giant cells found in tissues, saliva, sputum, urine sediment and cerebrospinal fluid. The cells have intranuclear and cytoplasmic inclusions and contain a multiplying virus. Changes in the nucleus of the cell give it a resemblance to an owl's eye. Giant cells are localized primarily in the epithelium of the excretory ducts of the salivary glands, in the epithelium of the distal parts of the nephron in the kidneys, in the epithelium of the bile ducts in the liver, and in the epithelium of the ependyma of the ventricles of the brain.

In response to CMV exposure, the surrounding interstitial tissue develops lymphohistiocytic infiltrates, sometimes having the character of nodules. In the generalized form, damage to the lungs, kidneys and intestines is more common, and less often to the liver and other organs. Along with giant cells and lymphohistiocytic infiltrates, a picture of interstitial pneumonia is found in the lungs, interstitial nephritis in the kidneys, ulcerative enterocolitis in the intestines, and cholestatic hepatitis in the liver.

Congenital generalized CMV infection is also characterized by hemorrhagic rashes on the skin and mucous membranes, hemorrhages in the internal organs and brain, significant anemia, and the development of foci of myelo-erythroblastosis in the liver, spleen and kidneys. Eye damage is also noted - uveitis, lens opacification and iris subatrophy.

Rice. 1-6. Salivary gland tissue. Focal venous-capillary plethora. In the stroma of the gland there are focal round cell (lymphoid) infiltrates. In the epithelium of the ducts there are groups of large round cytomegalic cells, similar to an “owl’s eye”, with a large round nucleus and a narrow rim of light cytoplasm. Staining: hematoxylin-eosin. Magnification x250, subsequent computer processing of the image in the form of cropping a fragment.

Classification of CMVI (A.P. Kazantsev, N.I. Popova, 1980):

congenital CMV - acute form, chronic form;
acquired CMVI - latent form, acute mononucleosis-like form, generalized form.

Clinic for CMV infection in children

Acute form congenital CMV. The clinic of the acute form of CMV is characterized by the most severe course with pronounced signs of toxicosis, enlarged liver and spleen, thrombocytopenia, hemorrhagic syndrome, changes in the blood count and damage to the central nervous system. This form of the disease is often called fetal cytomegalovirus syndrome. Children are born premature, with low body weight, reflexes are depressed, and sometimes there are disturbances in the acts of sucking and swallowing. Occurs in 60% of cases jaundice, possible causes of which may be CMV hepatitis or increased hemolysis of red blood cells. Jaundice resembles physiological jaundice, but the intensity of the disease gradually increases, and it persists for 1-2 months. In 90% of children, the liver is enlarged and protrudes 3-5 cm below the edge of the costal arch. The spleen is enlarged in 42% of cases, it is dense and painless. Thrombocytopenia is observed in the blood of 70% of children, increased content bilirubin, as well as an increase in the activity of transaminases - up to 150 IU/l and alkaline phosphatase - up to 28 IU.

The acute form of CMV occurs under the guise of hemolytic disease of the newborn. Often also found gastrointestinal lesions, prevail dyspeptic syndrome and progressive dystrophy.

In the acute form of congenital CMV, the death of children occurs in the first weeks or months of life, most often from associated bacterial infections.

Chronic form of congenital CMV. Children who have had an acute form of the disease experience an undulating course of the chronic form of CMV infection. Often formed congenital malformations of the central nervous system, in particular microcephaly- in 40% of cases. May develop chronic hepatitis, in rare cases turning into cirrhosis. Changes in the lungs in 25% of children are characterized by development pneumosclerosis and fibrosis.

Differential diagnosis of congenital CMV infection is carried out with rubella, listeriosis, toxoplasmosis, as well as hemolytic disease newborns, congenital syphilis and sepsis.

Latent form of acquired CMV infection. The latent form does not manifest itself clinically and is detected only during a virological examination.

Acute mononucleosis-like form of acquired CMV infection. The acute form, in clinical manifestations in older children, resembles Infectious mononucleosis and often occurs after blood transfusions. The disease is characterized by an acute onset with a rise in temperature and the appearance of symptoms of intoxication. Lymphadenopathy, pain on palpation of the parotid region, symptoms of acute respiratory infections, and hepatomegaly are recorded. Characterized by leukocytosis, an increase in the number of neutrophilic granulocytes and atypical mononuclear cells. It is recommended to perform the Paul-Bunnel and Hoff-Bauer reactions, which are positive in the case of infectious mononucleosis and negative in the case of cytomegalovirus mononucleosis-like syndrome.

Generalized form of acquired CMV infection. The generalized form is characterized by lymphadenopathy, intoxication, and increased body temperature. The earliest symptoms of respiratory damage are detected: dry painful cough, shortness of breath of mixed type. Auscultation reveals dry and moist rales in the lungs. Developing pneumonia is characterized protracted course, which determines the severity of the underlying disease. Due to the layering of bacterial and fungal infections, it can be difficult to distinguish the symptoms of generalized CMV infection.

CMV often occurs in association with other viral or bacterial etiology. The combination of CMV and ARVI is especially common, in which cytomegalovirus is isolated in 30% of sick children. This type of flu occurs in a more severe form and promotes the activation of CMV infection by suppressing immune reactions.

CMV clinic in adults

CMV infection in adults occurs in latent (localized) and generalized forms. Latent form usually does not appear clearly clinical symptoms. Sometimes observed mild flu-like illness, vague low-grade fever. Diagnosis of this form of CMV is based on the results laboratory research.

Generalized form acquired CMV in adults is observed rarely. As a rule, its clinical signs are detected against the background of some other disease that sharply reduces immunity: after severe surgical operations, against the background of leukemia or neoplasms. In these cases, the use of various immunosuppressants in the treatment of patients is of pathogenetic importance. Generalized CMV in adults is manifested by sluggish pneumonia or a peculiar acute infectious disease characterized by fever, enlarged and painful liver, an increase in the number of mononuclear cells in the blood (mononucleosis caused by CMV), and damage to the gastrointestinal tract. Lymphadenopathy and tonsillitis are absent.

Diagnosing the disease is difficult. In women, latent CMV infection can be suspected when repeated miscarriages and stillbirths children. The diagnosis is based on data from cytological and virological studies.

Liver pathology occupies a special place in CMV disease. Cytomegalovirus hepatitis, developing in response to the introduction of CMV, is characterized by degeneration of the biliary tract epithelium and hepatocytes, stellate endothelial cells and vascular endothelium. They form cytomegalic cells, surrounded by inflammatory mononuclear infiltrates. The combination of these changes leads to intrahepatic cholestasis. Cytomegalic cells desquamate and fill the lumens of the bile ducts, being cause of the mechanical component of jaundice. At the same time, degenerated CMV hepatocytes are destructively changed, up to necrosis, which causes the development cytolysis syndrome. It should be noted that in case of CMV hepatitis, which has a prolonged, subacute or chronic course, the leading role belongs to cholestasis syndrome. In diagnostics CMV hepatitis great importance have the results of a puncture biopsy of the liver (detection in the punctate of giant, 25-40 µm in diameter, cytomegalic cells in the form of an owl's eye with a huge nucleus and a narrow border of cytoplasm), as well as cytological (detection of cytomegalic cells in urine sediment) and serological (detection of IgM antibodies to CMVI) methods. Differential diagnosis CMV hepatitis is carried out with other viral hepatitis: B, Epstein-Barr, herpetic hepatitis.

With CMV, are usually affected salivary glands . Mononuclear infiltrates are found in them. Sialadenitis wears chronic nature. Simultaneously with damage to the salivary glands, degeneration of the epithelium of the stomach and intestines is observed with the development of erosions and ulcers and lymphohistiocytic infiltrates in the thickness of the intestinal wall.

Damage to the lymph nodes is characteristic of CMV infection. At the same time, all the typical signs of this infection remain. It is the pathology of the lymphatic system that aggravates the organ and systemic manifestations of CMV infection.

Damage to the respiratory organs in CMV infection is characterized by the development interstitial pneumonia, bronchitis, bronchiolitis. In this case, the epithelium of the alveoli, bronchi, bronchioles and surrounding lymph nodes undergoes specific changes. Infiltrates of mononuclear cells, macrophages and plasma cells are formed in the peribronchial tissue. CMV pneumonia often occurs with a staphylococcal layer, accompanied by purulent bronchiolitis and abscess formation. The presence of CMV is confirmed by the detection of cytomegalic cells. Often CMV pneumonia is combined with pneumocystis with an extremely severe course of the disease.

Kidney damage with CMV infection is also common. In this case, the cells of the epithelium of the convoluted tubules, the epithelium of the capsules of the glomeruli, as well as the ureters and Bladder. This explains the detection of cytomegalic cells in urine sediment.

Damage to the central nervous system in adults is rare and occurs in the form of subacute encephalitis.

Eye lesions with CMV infection are characterized by the development chorioretinitis. Chorioretinitis is very often combined with CMV encephalitis.

Laboratory diagnostics

Currently, there are several reliable methods for determining CMV.

Traditional isolation of the virus on a culture of embryonic fibroblasts and a culture of human diploid cells in which CMV exhibits its cytopathic effect. The method is the most reliable and sensitive (determination time is 2-3 weeks).
An accelerated method of culturing the virus for 6 hours using monoclonal antibodies to indicate early antigens.
The method of cytoscopy of sediments of urine and saliva, as well as light and electron microscopy of histological preparations, in particular liver biopsy, allows identifying giant CMV cells in the form of an owl's eye, with a narrow border of cytoplasm and a large nucleus.

Various methods are used to detect antibodies to CMV.

Complement fixation reaction (CFR). The most common way to study a specific humoral immunity with CMV. The method is not sensitive enough, since only total antibodies are detected. RSC with a titer of 1:4 is negative, 1:8 is weakly positive, 1:16 is positive, 1:32 is strongly positive.
Immunofluorescence analysis. Determines an increase in the titer of Ig antibodies of classes M and G to CMV. This method is more sensitive compared to RSC.
Enzyme immunosorbent (peroxidase) analysis.
Solid-phase radioimmunoassay. It also allows you to determine Ig classes M and G.
Immunoblotting. Using polyacrylamide gel electrophoresis, he evaluates antibodies to CMV of various classes. This most modern method specific diagnostics, it can be used to determine the entire spectrum of antibodies to CMV.

With congenital CMV with damage to the central nervous system, the prognosis is unfavorable, while with acquired generalized CMV it is determined by the underlying disease. With the latent form of acquired CMV, the prognosis is favorable.

Prevention

It is necessary to exclude contact between pregnant women and children with congenital CMV infection. If a woman gives birth to a child with congenital CMV next pregnancy may be recommended no earlier than 2 years(term of virus persistence in localized acquired CMV infection).

Currently, an active search for vaccines against CMV is underway. Already created in the USA and Great Britain live vaccines, which are currently undergoing clinical trials.

It is important to remember that CMV infection requires doctors to be knowledgeable in a variety of areas of medicine and creative search for the effective use of proven methods of diagnosis, treatment and prevention. Early detection of CMV infection helps to increase the effectiveness of care for this category of patients, as well as timely recognition of cases of HIV infection and AIDS.

Literature

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Demidova S. A., Semenova E. I., Zhdanov V. M., Gavrilov V. I. Human cytomegalovirus infection. - M.: Medicine, 1976.
Farber N.A. Cytomegalovirus infection in clinical medicine//Ter. Archive, 1989. - No. 11.
Farber N. A. Cytomegalovirus infection and pregnancy // Obstetrics and gynecology. - 1989. - No. 12.
Samokhin P. A. Cytomegalovirus infection in children. - M.: Medicine, 1987.
Kazantsev A.P., Popova N.I. Intrauterine infectious diseases and their prevention. - L.: Medicine, 1980.
Report of the WHO scientific group “Immunological deficiency”. - M.: Medicine, 1980.
Kozlova S. I., Semanova E., Demikova N. S., Blinnikova O. E. Hereditary syndromes and medical genetic counseling. - L.: Medicine, 1987.
Harrison J. Guide to internal medicine: In 10 volumes - 1998. - T. 5.
Lawlor Jr. G., Fisher T., Adelman D. Clinical immunology and allergology. - M.: Praktika, 2000.

Structure of deaths and pathological anatomy

in patients with HIV infection in Moscow

Infectious Clinical Hospital No. 2

Federal Center for Prevention and Control of AIDS, Ministry of Health of the Russian Federation, Institute of Human Morphology of the Russian Academy of Medical Sciences, Moscow

Materials and methods

In the period from 1991 to 2003. 537 adult patients with HIV infection died and were admitted to the pathology department of ICH No. 2. Mortality was recorded in all age groups, 65% were persons under 40 years of age. Among the dead patients, 75% were men. In all autopsy cases, a complete macroscopic and microscopic examination using a wide range of histological stains, bacteriological and virological methods.

The second place in the frequency of detection of HIV infection in deceased patients over a 13-year observation period is occupied by cytomegalovirus infection (CMVI) - 85 cases (15.8%). Until 1999 Every year, at least a quarter of patients who died suffered from CMV infection. The highest proportion of CMV infection, according to sectional studies, was recorded in 1997. - 35.8% of cases. From 2000 to 2002 the frequency of CMV as a cause of death decreased and ranged from 9.7% to 6.5% per year, which may have been a consequence of timely detection of the fact of active replication of CMV in an HIV-infected patient and drug prophylaxis of manifest forms of the disease, as well as - timely etiotropic therapy of patients with clinically significant CMV infection. In 2003 the frequency of CMV infection in dead patients increased again to 14.5%, primarily due to patients who applied for the first time medical care, already having a severe generalized disease of cytomegalovirus etiology. Has been associated with CMV wide range organ lesions, including pathology of the lungs, intestines, esophagus, adrenal glands, retina, brain and spinal cord, liver, stomach, lymph nodes, kidneys, spleen, heart, pancreas. With a wide variety of lesions of cytomegalovirus etiology, there is a unique morphology of lesions that is not found in other well-known infectious diseases. An important part of the pathogenesis of CMV infection in patients with HIV infection is generalized damage to the vascular endothelium by cytomegalovirus, which occurs in all affected organs and leads to chronic ischemia. Also characteristic feature diseases should be considered development widespread fibrosis with various variants of dysregenerative and precancerous changes. Should be paid Special attention on frequent and often the only detected extensive lesion adrenal glands in patients with CMV infection at autopsy. In all cases, the pathological process had bilateral character, in a number of observations covering all layers of the crust and medulla with complete destruction of organ tissue. Despite the high incidence and severity of adrenal lesions, clinical diagnosis Adrenal insufficiency was not diagnosed in any case. In two patients, acute adrenal insufficiency was the immediate cause of death.

Cytomegalovirus hepatitis is the leading clinical manifestation of congenital cytomegalovirus infection. Liver damage during cytomegalovirus infection is always a sign of a generalized process.

What causes Cytomegalovirus hepatitis:

The causative agent of cytomegalovirus infection- DNA genomic virus of the genus Cytomegalovirus (Cytomegalovirus hominis) subfamily Betaherpesvirinae of the Herpesviridae family. There are 3 known strains of the virus: Davis, AD-169 and Kerr. Slow reproduction of the virus in a cell is possible without damaging it. The virus is inactivated by heating and freezing and is well preserved at room temperature. Stable at - 90 °C long time, is relatively stable at pH 5.0-9.0 and is rapidly destroyed at pH 3.0.

Reservoir and source of infection- a person with an acute or latent form of the disease. The virus can be found in various biological secretions: saliva, nasopharyngeal secretions, tears, urine, feces, seminal fluid, cervical secretions.

Transmission mechanisms diverse, transmission routes- airborne, contact (direct and indirect - through household items) and transplacental. Infection is possible through sexual contact, through internal organ transplants (kidneys or hearts) and blood transfusions from an infected donor. Intrapartum infection of a child is observed much more often than transplacental infection. Infection of the mother is most dangerous for the fetus in the first trimester of pregnancy. In such situations, the incidence of intrauterine development disorders is highest.

Natural sensitivity of people high but widespread latent infection. Clinical manifestations infections classified as opportunistic diseases are possible in conditions of primary or secondary immunodeficiency.

Main epidemiological signs of cytomegalovirus infection. The disease is registered everywhere; its widespread distribution is evidenced by antiviral antibodies detected in 50-80% of adults. The variety of routes of CMV infection 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 transfusiology, perinatal pathology may cause prematurity, stillbirths, birth defects development. In adults, CMV infection is encountered as a concomitant disease in various immunodeficiency states. Ongoing pollution environment, the use of cytostatics and immunosuppressants contribute to an increase in the incidence 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 likelihood of intrauterine infection is much higher when a woman is initially infected during pregnancy. No seasonal or occupational characteristics of morbidity were identified.

Pathogenesis (what happens?) during Cytomegalovirus hepatitis:

With various routes of transmission, the mucous membranes of the upper respiratory tract, gastrointestinal tract or genital organs. The virus enters the blood; short-term viremia quickly ends with localization of the pathogen upon penetration into leukocytes and mononuclear phagocytes, where its replication occurs. Infected cells increase in size (cytomegaly) and acquire a typical morphology with nuclear inclusions representing accumulations of the virus. The formation of cytomegalic 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 persist for a long time and latently 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 direct effects on T lymphocytes. In various immunodeficiency states (in early childhood, during pregnancy, use of cytostatics and immunosuppressants, HIV infection) and especially in cases of disorders cellular immunity, further aggravated by the direct impact of the virus, reactivation of the pathogen and its hematogenous generalization with damage to almost all organs and systems are possible. In this case, the epitheliotropy of the virus is of great importance. It is especially pronounced in relation to the epithelium of the salivary glands, which, under the influence of the virus, turns into cytomegalic cells.

Liver pathology occupies a special place in CMV disease. 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 endothelial cells and vascular endothelium. They form cytomegalic cells, surrounded by inflammatory mononuclear infiltrates. The combination of these changes leads to intrahepatic cholestasis. Cytomegalic cells desquamate and fill the lumens of the bile ducts, causing the mechanical component of jaundice. At the same time, degenerated CMV hepatocytes are destructively altered to the point of necrosis, causing the development of cytolysis syndrome. It should be noted that in CMV hepatitis, which has a prolonged, subacute or chronic course, cholestasis syndrome plays a leading role.

Symptoms of Cytomegalovirus hepatitis:

Cytomegalovirus hepatitis can occur in anicteric and icteric forms.

Anicteric form CMV hepatitis occurs with very poor clinical symptoms, the children's condition remains satisfactory. Detection of the anicteric form of hepatitis is possible in connection with the detection of hepatomegaly and higher level aminotransferases. The activity of aminotransferases increases slightly (1.5-2.0 times) with a predominance of AST over ALT.

With the icteric form of hepatitis, two groups of patients were identified: 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 the icteric form of CMV hepatitis is not significantly affected. They have hepatosplenomegaly. Jaundice in most children was detected in the first days after birth.

Jaundice form CMV hepatitis with a favorable course is characterized by mild jaundice skin, dark urine and colored feces, hepatosplenomegaly, moderate hyperfermentemia with a predominance of AST over ALT, increased bilirubin levels with a predominance of the direct fraction, as well as the presence of markers of active CMV replication.

One of the variants of cytomegalovirus liver damage in congenital CMV is formation of biliary cirrhosis of the liver, leading to death, usually in the 2nd half of the first year of life.

Children born with cytomegalovirus hepatitis have low Apgar scores (a scale reflecting the state of the child’s nervous system at the time of birth), insufficient muscle development, and increased or decreased muscle tone. There may be short-term muscle twitching or cramps, the baby does not latch onto the breast, and all innate reflexes are reduced. In general, the condition of such a child will be severe and will be pronounced hemorrhagic syndrome(nosebleeds, gastrointestinal bleeding, hemorrhagic rash on the skin and mucous membranes), the number of red blood cells and platelets in the blood decreases, the central nervous system is affected. Yellowness of the skin, mucous membranes and sclera appears in 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 and have shortness of breath. Soon signs of hydrocephalus or microcephaly, mental retardation, damage to the optic nerves, kidneys, stomach and intestines may appear. Hepatocellular enzymes in the blood will be sharply increased, protein and the albumin fraction of protein will be decreased. This process often ends in death. In a benign course, jaundice remains for 2–3 months, after which it begins to subside.

Diagnosis of Cytomegalovirus hepatitis:

Diagnosis of cytomegalovirus hepatitis was established on the basis of anamnestic, clinical and biochemical data with mandatory confirmation of the diagnosis by detection of CMV markers. Markers of parenteral viral hepatitis were examined in all patients.

In the diagnosis of cytomegalovirus hepatitis, the results of a puncture biopsy of the liver are of great importance (detection in the puncture of giant, 25–40 μm in diameter, cytomegalic cells in the form of an owl's eye with a huge nucleus and a narrow border of cytoplasm), as well as the cytological method (detection of cytomegalic cells in the urine sediment) and serological method (detection of antibodies – Ig M to CMV). Differential diagnosis of CMV hepatitis is carried out with other viral hepatitis: B, Epstein-Barr, herpetic hepatitis.

A biochemical blood test reveals a clear hyperenzymemia with a predominance of AST (160.0±25.6 µmol/min.l) over ALT (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).

We invite you to read the article on the topic: “Cytomegalovirus hepatitis” on our website dedicated to liver treatment.

One of the common and dangerous liver lesions is cytomegalovirus hepatitis. This disease is caused by the herpes virus. The disease is asymptomatic or has mild symptoms such as yellowing of the skin, enlargement of the liver and spleen, and darkening of the urine. If a cytomegalovirus infection occurs, you must immediately go to the hospital, undergo examination and begin treatment, as this threatens the spread of infection throughout the body and disease of many organs.

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What kind of disease is this?

Cytomegalovirus hepatitis is a liver disease caused by cytomegalovirus. Such liver damage is considered an expression of symptoms of a congenital variant of cytomegalovirus infection. If the virus enters the human body, it remains in it all life and becomes very active when it decreases. protective forces body. When the liver is damaged by such a virus, the cells of the organ change and its functioning is disrupted.

Diagnosis of pathology is difficult to carry out, since the disease has many similarities with other diseases.

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Causes and type of disease

The virus is activated against the background of a decrease in the body’s defenses.

The main cause of liver damage is cytomegalovirus, which is transmitted through the placenta from an infected mother to the child or from a person through saliva, urine and blood. Acquired through blood transfusion or organ transplantation. The following causes of cytomegalovirus hepatitis are also identified:

decreased immunity;
presence of HIV infection;
treatment with immunosuppressive drugs;
presence of chronic diseases.

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Features of the flow

When a virus enters the body, the immune system reduces its activity. In this case, the pathology does not manifest itself in any way. In another case, the pathology may occur in the form of symptoms similar to mononucleosis: sore throat, prolonged rise in temperature, severe fatigue. The virus enters the body through the nose, mouth, lungs, intestines and genitals. The virus then enters the bloodstream and multiplies in white blood cells. When it enters the lymphoid tissue, it exists for a long time in a latent form. If immunity decreases, the virus is activated, and vivid symptoms of the disease develop.

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Types of diseases and their symptoms

Acute form of the disease

Active spread of the virus disrupts liver function.

The acute form is manifested by the following symptoms:

Pre-icteric period. Patients experience decreased appetite and intoxication of the body. The duration of the phase is from 3 days to a week.
Jaundice period. There is an increase in intoxication, abdominal pain, yellowing of the skin and intestinal upset. The phase lasts from 2 to 4 weeks.
Post-icteric period. Patients feel normal, the liver and spleen become normal sizes, laboratory tests are returning to normal.

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Chronic form

If hepatitis has become chronic, it does not manifest itself with any special symptoms and the disease in this case proceeds sluggishly:

there are no distinctive indicators in the analyzes;
the development of liver fibrosis is detected;
intoxication is reduced.

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Congenital form

Infection of the fetus occurs in the womb.

The congenital form of the disease occurs when the virus penetrates the placenta from mother to child. In this case, the newborn may develop biliary cirrhosis, which is the leading cause of death. Also, CMV hepatitis in children occurs in icteric and anicteric forms. Concomitant factors for the development of hepatitis in a newborn are:

neurodevelopmental disorder;
elevated or decreased tone muscles;
the appearance of seizures;
reduced innate reflexes.

Symptoms of cytomegalovirus with congenital form:

baby's refusal to breastfeed;
nosebleeds;
the appearance of a hemorrhagic rash;
the appearance of yellowness of the skin;
enlargement of the spleen and liver.

Cytomegalovirus appears already in the first days of life.

The icteric form of the disease occurs in 2 variants:

Good luck with recovery.
Progression of the disease and transition to biliary cirrhosis, which often leads to death.

Cytomegalovirus jaundice in newborns may not cause yellowing of the skin. In this case, the symptoms of the disease are mild, almost unnoticeable, and the children are in a satisfactory condition. A thorough examination of the child reveals an enlargement of the liver and spleen, and test results indicate an increase in liver enzymes.

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Other types

There is also an acquired form of the disease. It can occur in 2 types: acute and chronic. The incubation period for acute cases lasts from 2 to 3 months. In this case, the disease can occur in anicteric, mild, moderate and severe form. The acute period is manifested by pronounced symptoms, and when it becomes chronic, the disease is characterized by a sluggish course and does not have pronounced symptoms.

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Which doctor should I see?

If the patient experiences discomfort in the right hypochondrium, or develops pronounced symptoms of the disease, he needs to consult a gastroenterologist and infectious disease specialist. Doctors will listen and record the patient’s complaints and conduct an objective examination. To exclude concomitant diseases, they will send you for examination to other specialists, and will also give you a referral for special tests and laboratory tests in order to make an accurate diagnosis.

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Diagnostic measures

Laboratory tests will help to accurately determine the type of causative agent of the disease.

For the ruling correct diagnosis and conducting effective treatment patients need to go to hospital. At the hospital, doctors will take a history of the disease and conduct an examination. Upon examination, yellowness of the skin and an increase in the size of the liver and spleen are revealed. Patients also complain of increased body temperature, darkening of urine and lightening of stool. Doctors then order tests and laboratory tests, such as:

general urine and blood tests;
blood biochemistry;
virus marker analysis;
test for antibodies to the virus;
cytological examination of urine sediment;
liver biopsy;
Ultrasound of the abdominal cavity.

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Treatment of hepatitis and CMV pathology

Cytomegalovirus hepatitis is very dangerous disease for human life. Therefore, treatment cannot be carried out at home without medical supervision. If symptoms appear, you should consult a doctor to undergo a proper and thorough examination. . After determining an accurate diagnosis, the doctor will prescribe adequate treatment. Drug therapy is prescribed as treatment.

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Drug treatment

For the treatment of cytomegalovirus hepatitis, the drugs presented in the table are prescribed:

To effectively treat the disease, you need to monitor the state of the immune system and adhere to the regimen drug treatment. It is imperative to enrich food with vitamins and minerals, lead active image life. It is also necessary to avoid contact with sick people, physical and mental fatigue and not succumb to stress factors. If you experience any discomfort in the liver area, you should consult your doctor.

Hepatitis B virus and cytomegalovirus, like HIV, cause chronic infection. These viruses are transmitted through blood and genital secretions. They are characterized by injection and transplacental mechanisms, as well as sexual transmission of infection. Cytomegalovirus can be transmitted through saliva. The hepatitis C virus is transmitted primarily through blood. Sexual transmission of the hepatitis C virus is also possible, but its role is small. Most sexual partners of persons infected with the virus hepatitis C does not become infected. All of the viruses mentioned cause a primary infection, which in most cases is asymptomatic. Followed by chronic infection, which can lead to severe complications over several years or decades. In contrast, the hepatitis A virus usually causes acute hepatitis, very rarely chronic hepatitis. The hepatitis A virus is characterized by a fecal-oral transmission mechanism. It is not transmitted through blood.

HepatitisA

In the United States, 125,000–200,000 cases of hepatitis A are registered annually. Antibodies to the hepatitis A virus are detected in 15-25% of Americans. This disease is characterized by a fecal-oral transmission mechanism, especially among children. The sexual route of infection with the hepatitis A virus is typical for homosexuals and bisexual men. This group accounts for the majority of hepatitis A cases among adults.

Clinical picture

The incubation period is usually 3-5 weeks. In adults, the disease in most cases occurs with a clinical picture. In 90% of cases, hepatitis A is asymptomatic in children. Main manifestations include jaundice and hepatomegaly. Resolution of symptoms and normalization of biochemical parameters of liver function usually occur within 6 weeks from the onset of the disease (sometimes up to 3 months). Sometimes fulminant hepatitis with liver failure occurs.

Diagnostics

Diagnosis is based on the clinical picture and biochemical indicators of liver function (AST, ALT) plus serological tests for antibodies to the hepatitis A virus. There are no methods for detecting hepatitis A virus antigens yet. IgM to the hepatitis A virus indicates a recent infection; it is detected in the period from 3 weeks to 4 months from the moment of infection. IgC to the hepatitis A virus is detected 6 weeks after infection; it persists indefinitely.

Prevention

Active immunization against hepatitis A is indicated (with negative serological reactions to hepatitis A): (1) homosexuals and bisexual men; (2) at high risk infection (for example, before traveling to countries with a high incidence of hepatitis A); (3) after contact with a patient with hepatitis A. For adults, active immunization is carried out twice with an interval of 6-12 months. In addition, after contact with a patient with hepatitis A (no later than 2 weeks), immunoglobulin against hepatitis A is prescribed, 0.02 ml/kg body weight IM. The use of condoms and avoidance of sexual intercourse, in which the fecal-oral mechanism of transmission of infection is possible, helps prevent infection through sexual contact.

Hepatitis B

Epidemiology and routes of infection

Incidence and prevalence can vary greatly. In the United States, 140,000–320,000 new cases of hepatitis B are registered annually. In total, there are about 750,000 patients with chronic hepatitis B in the United States. Injection and transplacental mechanisms, as well as sexual transmission of the infection, are typical. During sexual intercourse, the risk of infection is greatest during anal sex. The highest incidence is observed among homosexuals and bisexual men, as well as among injection drug users. In the United States, 45% of cases of hepatitis B infection are caused by heterosexual contacts; 15% of cases are caused by homosexual contacts.

Clinical picture

The incubation period is usually 6-12 weeks. In most cases (36-70%), the primary infection occurs with a clinical picture, but the symptoms are usually nonspecific. These include nausea, anorexia, jaundice and hepatomegaly. In 15-20% of cases, prodromal phenomena of the serum sickness type are observed, including rash, polyarthritis, and symptoms of cryoglobulinemia. Chronic hepatitis B is usually asymptomatic until cirrhosis or hepatic cell carcinoma develops. In this case, there may be no biochemical and histological (during biopsy) signs of active hepatitis.

Diagnostics

Diagnosis is usually based on serological tests. Hepatitis B virus surface antigen (HbsAg) is detected; antibodies to the surface antigen of the hepatitis B virus (anti-HbsAg antibodies); hepatitis B virus nuclear antigen (HbcAg). HbsAg indicates acute or chronic active hepatitis IN; a patient with HbsAg is contagious. Anti-HbsAg antibodies usually indicate previous hepatitis B. Hepatitis B virus E antigen (HbeAg) is detected in serum during the period of active viral replication; the patient is highly contagious.

Prevention

The basis of prevention is immunization against hepatitis B. For adults, the hepatitis B vaccine is administered in a dose of 20 mg IM; repeat after 1 and 6 months. While there is no immunization in childhood, it is carried out for all adolescents, adults with STDs, as well as medical workers. Injecting drug addicts, homosexuals and bisexual men are actively immunized against hepatitis B with negative serological reactions. In this case, it is advisable to administer the first dose of the vaccine on the day of blood collection for serological tests. Subsequent doses depend on results serological reactions. Using condoms helps prevent infection during sexual intercourse.

Hepatitis C

Epidemiology and routes of infection

In the United States, hepatitis C accounts for 15% of all acute hepatitis. In the United States, 30,000–40,000 new cases of hepatitis C are registered annually. The disease is detected in 40% of patients with cirrhosis of the liver. In the United States, 8,000–10,000 people die annually from hepatitis C and its complications. Liver failure due to hepatitis C is the most common indication for liver transplantation. The injection mechanism of infection transmission and infection through blood transfusion are characteristic. Infections through sexual contact are possible, but rare.

Clinical picture

Acute hepatitis C is asymptomatic. Two-thirds of hepatitis C cases develop chronic hepatitis, which is usually asymptomatic until cirrhosis or liver failure develops.

Diagnostics

To detect antibodies to the hepatitis C virus, it is usually used linked immunosorbent assay. To confirm positive result immunoblotting is used. Reverse polymerase chain reaction allows you to evaluate " viral load" In addition, the function and degree of liver inflammation are assessed (ALT, biopsy).

Prevention

The basis of prevention is screening donors for antibodies to the hepatitis C virus, as well as reducing contact with other people’s blood (fighting drug addiction; measures to reduce the use of shared syringes by injection drug addicts). The use of condoms is ineffective in preventing hepatitis C. Mass examinations for hepatitis C are indicated for drug addicts and representatives of other risk groups. Examination of sexual partners of patients with hepatitis C is not advisable.

Cytomegalovirus

Epidemiology and routes of infection

Cytomegalovirus infection is widespread throughout the world. Infection is possible through genital secretions, saliva or blood. Intrauterine infection and infection during childbirth are possible. Antibodies to cytomegalovirus are detected in 10-15% of adolescents. By the age of 35, they are already detected in half of people. These indicators vary greatly among different regions and different population groups. Superinfection with other strains of cytomegalovirus is possible.

Clinical picture

In most cases, cytomegalovirus infection is asymptomatic. Sometimes granulomatous hepatitis or a syndrome resembling mononucleosis occurs. Intrauterine infection of a child, usually occurring when primary infection in a pregnant woman, can cause severe systemic diseases and congenital pathology Central nervous system (eg, sensorineural hearing loss). The role of cytomegalovirus infection in the development of atherosclerosis has not been fully elucidated. In patients with AIDS and in persons with severe immunodeficiency of another nature, a severe, sometimes life-threatening course of cytomegalovirus infection (retinitis, pneumonia, esophagitis, colitis, encephalitis) is possible.

Diagnostics

Testing of blood, urine and genital secretions using culture, antigen detection or DNA amplification techniques is of limited value in practical work. Serological tests are used. Histological and cytological studies are detected in cases of cytomegalovirus infection that occurs with a clinical picture. Interpretation of histological and cytological studies often difficult.

Prevention

Condoms prevent infection during sexual intercourse. Prevention of primary cytomegalovirus infection in pregnant women (using condoms, avoiding casual sex) helps prevent intrauterine infection of the child. Mass examinations and examination of sexual partners are not indicated.

Other viruses

Human herpesvirus type 8

Human herpesvirus type 8 is a new virus in the herpesvirus family that causes Kaposi's sarcoma in HIV-infected people. Epidemiological data and the detection of this virus in semen indicate the possibility of its transmission through sexual contact, especially among homosexual and bisexual men. However, other mechanisms of transmission of human herpesvirus type 8 cannot be excluded.

IN hepatitis virusD

The hepatitis D virus is an "incomplete" virus, causing disease only in the presence of the hepatitis B virus. Infection with the hepatitis D virus in a patient with hepatitis B is clinically manifested by an exacerbation of chronic hepatitis. Hepatitis D infection occurs through the blood. Infection through sexual contact is rare.

Epstein-Barr virus

Epstein-Barr virus, the causative agent of infectious mononucleosis, can be transmitted sexually. However, in most cases, infection with this virus is not associated with sexual contact and occurs through saliva. In an HIV-infected person, reactivation of the Epstein-Barr virus causes oral hairy leukoplakia.

Human T-lymphotropic virus 1

Human T-lymphotropic virus type 1 causes adult T-cell leukemia lymphoma and spastic paraparesis. The clinical picture of infection caused by human T-lymphotropic virus type 2 has not yet been clarified. The epidemiology of human T-lymphotropic virus types 1 and 2 is similar to the epidemiology of hepatitis B and C. Injection and transplacental mechanisms, as well as sexual transmission of infection, are characteristic.

Enteroviruses

Enteroviruses are usually transmitted through sexual contact, in which a fecal-oral transmission mechanism is possible.

Adenovirus type 19

Adenovirus type 19 causes acute conjunctivitis in combination with urethritis. Can be transmitted sexually.

Hunter Handsfield

Sexually transmitted diseases. Color atlas reference book. – M.: “Publishing house BINOM”, 2006.-296 p.: ill.

Nature of the disease

The causative agent of the disease is cytomegalovirus hominis - human herpes virus type V, HHV5, has several strains. This DNA virus survives well at room temperature and is sensitive to heat and freezing. Currently widespread. According to recent studies, about 80% of the world's population have specific antibodies in their blood. After infection, the virus can live in the host’s body for a long time without manifesting itself in any way, and remains in the person’s DNA throughout his life.

Etiology

Cytomegalovirus exclusively affects humans, with newborns and people with weakened immune systems especially susceptible. It can be found, as a rule, in the secretions of the salivary and lacrimal glands, nasopharynx, genitals and feces. The main routes of transmission of the virus:

domestic;
airborne;
sexual;
during organ transplants and blood transfusions;
from mother to child - in utero and through milk during feeding.

Pathogenesis

When the HHV5 virus enters the body, it bypasses the lymphatic system and immediately enters the blood. At the same time, it affects T-lymphocytes, suppressing immunity, and causes the proliferation of affected cells due to the growth of the nucleus and an increase in the volume of the cytoplasm. In hepatitis, cytomegalovirus integrates into the cells of the bile ducts and liver (hepatocytes), turning them into cytomegaloviruses. Foci of inflammation called mononuclear infiltrates form around such cells. Due to this, intrahepatic cholestasis arises - a decrease or cessation of bile secretion with its stagnation in the liver tissues. Often CMV infection progresses to the development of necrosis.

Concomitant diseases and possible complications

The CMV virus provokes not only hepatitis. Spreading through the bloodstream throughout the body, it damages the spleen, kidneys, lungs, spinal cord and causes serious complications, often leading to death. Pneumonia may develop against the background of cytomegalovirus hepatitis. It is characterized by localization inflammatory process in both lungs, dry cough with possible blood. Another common complication is cytomegalovirus retinitis - inflammation of the retina. It manifests itself in the form of decreased visual acuity and pain, first in one and then in both eyes. Incorrect treatment can lead to vision loss. By affecting the brain and spinal cord, the virus causes meningoencephalitis. This severe acute disease causes migraines, convulsions, paralysis, mental disorders, often ends in death.

Symptoms of CMV

Considering that the latent form of cytomegalovirus infection is more common, a person may not be aware of the presence of the virus in the body. Hepatitis CMV type can occur in acute or chronic form. The acute form of the disease, in turn, has an icteric or anicteric character. With an anicteric course, the patient suffers, first of all, from mononucleosis syndrome, similar to the signs of ARVI, which manifests itself:

loss of strength, decreased performance;
headache;
increased body temperature;
growth of lymph nodes;
increased sweating.

A yellow tint to the skin indicates an acute cytomegalovirus infection of the icteric type.

The icteric form of the disease is indicated, first of all, by a change in the color of the skin and whites of the eyes, the so-called jaundice. Urine becomes stained or discolored and feces, increased levels of bilirubin in the blood, heaviness or pain in the right hypochondrium. On palpation, an enlarged liver is observed. The acute form of cytomegalovirus hepatitis manifests itself during the first 2-3 months after infection, then the patient’s health becomes better, and a decrease in liver size is observed. However, in the absence of proper treatment during the incubation period, the disease becomes chronic. This trend is observed in 65% of patients. During the period of remission, the disease manifests itself only in a slight increase in the size of the liver and spleen.

Congenital hepatitis CMV type

Cytomegalovirus hepatitis can also be congenital. It occurs in newborn infants as a result of infection of the mother in the first trimester of pregnancy and is diagnosed in the first months of life. It is primarily chronic in nature and, as a rule, does not have pronounced symptoms. There is a thickening of the structure of the liver and the walls of the gallbladder, obstruction of the biliary tract. In infants suffering from this disease, the risk of developing liver fibrosis and cirrhosis increases significantly.

Diagnosis of cytomegalovirus infection and hepatitis

Only highly qualified infectious disease specialists and hepatologists can make a diagnosis of cytomegalovirus hepatitis after a thorough examination of the medical history and several laboratory tests. To detect IgG and IgM antibodies in the blood, a serological diagnostic method is used. In addition, it is shown biochemical analysis blood to study CMV markers and enzymes. In patients with CMV hepatitis, significant hyperfermentation is observed. The PCR method - polymerase chain reaction - is also considered an effective laboratory diagnostic method. It allows you to isolate the DNA of the virus in the genome of the carrier. Through cytological studies, cytomegallic cells can be detected in the urine. Final confirmation of the diagnosis is often possible after a liver biopsy. Pathological hepatocytes take the form of an “owl’s eye”; specific inclusions are visible in them.

Basic principles of treatment

To dock development of CMV virus at an early stage, special antiviral drugs are prescribed: Cidofovir, Foscarnet, Ganciclovir, Valganciclovir. Only a specialist can correctly determine the dosage and course of treatment. In the congenital form of the disease, as well as in the presence of other pathologies in the body, such as HIV infection, maintenance therapy by taking immunoglobulins is mandatory. In such cases, lifelong therapy aimed at suppressing viral replication is necessary. Diet No. 5 is recommended for patients with cytomegalovirus hepatitis, excluding fatty, fried, spicy and alcoholic foods.

In addition, patients with CMV infection are prescribed symptomatic treatment. In the presence of mononucleosis syndrome or pneumonia, antipyretics, such as Paracetamol or Ibuprofen, and cold medications are used. For cytomegalovirus retinitis: eye drops against retinal inflammation.

Preventive measures

A special vaccine against cytomegalovirus infection has not yet been invented, so it makes sense to regularly undergo examination by a doctor, take x-rays of the liver and biliary tract, because changes in their structure may indicate damage by the virus. Special risk Patients who are candidates for internal organ transplantation are susceptible to infection. Some time before the procedure, they should take a course of antiviral drugs. Any surgical interventions And cosmetic procedures must be carried out under completely sterile conditions, and all instruments must be thoroughly disinfected.

Materials:

Cytomegalovirus is a widespread causative agent of infection, which is usually asymptomatic.

Only occasionally does a disease resembling infectious mononucleosis or hepatitis develop. In immunocompromised patients, cytomegalovirus can cause severe generalized infection with multiple organ damage and high mortality. The virus is transmitted through contaminated saliva, urine and sometimes blood.

Once infected, the virus remains in the human body for life. The DNA of the virus is integrated into the genome of the host cells and remains in an inactive state most of the time. Periodically, cytomegalovirus is reactivated and at this time is found in saliva and urine. In healthy people, this process is completely controlled by the immune system, but if the immune system is weakened or after an organ transplant, an opportunistic infection can develop. In such patients, viremia can cause hepatitis, as well as damage to other organs. The cause of a relapse of infection can also be another strain of the virus, that is, a person can be a carrier of several strains of cytomegalovirus, which can be reactivated at different times.

Virus isolation. The virus is isolated from the urine, saliva, blood and tissues of patients. To properly collect and deliver samples for testing, you must contact the appropriate laboratory in advance.

Immune response. Primary infection is indicated by seroconversion. IgG antibodies to cytomegalovirus are absent in the acute phase of infection and appear later. If it was not possible to conduct a study in the acute phase, a high titer of IgG antibodies alone cannot serve as a sign of acute infection - this is only evidenced by the presence of specific IgM antibodies. With relapses of cytomegalovirus infection, an increase in the titer of IgM antibodies is observed only in a third of patients who have undergone transplantation, and is practically not observed in people with normal immunity. Therefore, in case of relapse, isolation of the pathogen may be necessary to confirm the diagnosis.

Primary cytomegalovirus infection. Liver damage during primary infection may be asymptomatic with slight promotion liver enzyme activity. In some cases, against the background of a slight or moderate increase in the activity of liver enzymes, symptoms of mild hepatitis are observed, which goes away on its own. Sometimes the disease is accompanied by hemolysis.

Infection with cytomegalovirus through blood transfusion. The virus is believed to be transmitted by white blood cells, including neutrophils. Hepatitis in most cases is accompanied by mononucleosis-like syndrome.

Transplantation. Cytomegalovirus infection is a common cause of hepatitis in transplant patients. The infection can enter the body through a transplanted organ, through a blood transfusion, or as a result of reactivation of the virus due to immunosuppression. In such patients, chronic asymptomatic liver damage is also possible.

To isolate the pathogen, a liver biopsy is performed. Typically, characteristic intranuclear inclusions (“owl eyes”) are visible in hepatocytes, and granulomas without caseous necrosis and other signs of granulomatous inflammation can be found in the liver parenchyma.

It remains controversial whether cytomegalovirus can cause extensive liver necrosis. There is no evidence that the virus causes chronic hepatitis in people with normal immunity. However, with impaired immunity (for example, with AIDS), severe chronic damage to the liver and biliary tract is possible. Cases of mixed infection with hepatitis B virus and cytomegalovirus have been described.

In confirmed cases, ganciclovir is prescribed. AIDS may require lifelong treatment.

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Cytomegalovirus hepatitis is an acute form of cytomegalovirus infection, leading to irreversible pathological changes in the liver tissue and biliary tract. The disease does not have a clearly defined endemic zone and is equally common in all social groups. As a rule, it does not have its own pronounced symptoms, so it can be mistaken for hepatitis.

Nature of the disease

Etiology

People with reduced immunity are at risk.

domestic;
airborne;
sexual;
during organ transplants and blood transfusions;
from mother to child - in utero and through milk during feeding.

Pathogenesis

Concomitant diseases and possible complications

There is a high risk of developing pneumonia due to cytomegalovirus infection.

The CMV virus provokes not only hepatitis. Spreading through the bloodstream throughout the body, it damages the spleen, kidneys, lungs, spinal cord and causes serious complications, often leading to death. Pneumonia may develop against the background of cytomegalovirus hepatitis. It is characterized by the localization of the inflammatory process in both lungs, a dry cough with a possible admixture of blood. Another common complication is cytomegalovirus retinitis - inflammation of the retina. It manifests itself in the form of decreased visual acuity and pain, first in one and then in both eyes. Incorrect treatment can lead to vision loss. By affecting the brain and spinal cord, the virus causes meningoencephalitis. This severe acute disease causes migraines, convulsions, paralysis, mental disorders, and often ends in death.

Symptoms of CMV

loss of strength, decreased performance;
headache;
increased body temperature;
growth of lymph nodes;
increased sweating.

A yellow tint to the skin indicates an acute cytomegalovirus infection of the icteric type.

The icteric form of the disease is indicated, first of all, by a change in the color of the skin and whites of the eyes, the so-called jaundice. There is staining or discoloration of urine and feces, an increase in the level of bilirubin in the blood, heaviness or pain in the right hypochondrium. On palpation, an enlarged liver is observed. The acute form of cytomegalovirus hepatitis manifests itself during the first 2-3 months after infection, then the patient’s health becomes better, and a decrease in liver size is observed. However, in the absence of proper treatment during the incubation period, the disease becomes chronic. This trend is observed in 65% of patients. During the period of remission, the disease manifests itself only in a slight increase in the size of the liver and spleen.

Congenital hepatitis CMV type

Diagnosis of cytomegalovirus infection and hepatitis

The disease can only be determined using a complex of laboratory and instrumental diagnostics.

Only highly qualified infectious disease specialists and hepatologists can make a diagnosis of cytomegalovirus hepatitis after a thorough examination of the medical history and several laboratory tests. To detect IgG and IgM antibodies in the blood, a serological diagnostic method is used. In addition, a biochemical blood test is indicated to study CMV markers and enzymes. In patients with CMV hepatitis, significant hyperfermentation is observed. The PCR method - polymerase chain reaction - is also considered an effective laboratory diagnostic method. It allows you to isolate the DNA of the virus in the genome of the carrier. Through cytological studies, cytomegallic cells can be detected in the urine. Final confirmation of the diagnosis is often possible after a liver biopsy. Pathological hepatocytes take the form of an “owl’s eye”; specific inclusions are visible in them.