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The article presents current data on the state of the issue of Hepatitis A (HA) in children in the Russian Federation and describes clinical and epidemiologic features of rare cases of severe course of the disease, as well as pathogenetic mechanisms of liver damage mediated by cell immune response. Objective. To identify clinical and epidemiologic features of the modern course of HA and its outcomes in children of Saint Petersburg within the period of 2018— 2023. Materials and methods. The study included 89 children diagnosed with HA, undergoing treatment at the Children's Research and Clinical Center for Infectious Diseases from 2018 to 2023. The analysis of disease progression in this group of patients was presented using clinical-anamnestic, epidemiologic, biochemical, virologic and instrumental data. Results. The analysis of infection sources showed a high frequency of HA infection within the family (44.9 ± 0.8%) and significantly less in childcare facilities and schools (7.9 ± 1.0%). The frequency of children with unidentified sources of infection remained high (47.2 ± 0.7%). One-third of all disease cases were imported from southern regions. Most hospitalized children had icteric HA (64.0 ± 0.6%) of moderate severity (79.8 ± 0.5%). Severe HA was observed in 6 patients (6.7 ± 1.0%). During the study, 17 patients (19.1 ± 0.9%) had a prolonged, complicated course of the disease, including ascites and aplastic anemia (12.6 ± 2.2%). Ascites was found in 4 patients with severe severity and in 5 patients with moderate severity of HA. Conclusions. Currently, there is an upward trend in the incidence of HA in the Russian Federation and Saint Petersburg, especially among schoolchildren (56.2%). A rather high frequency of severe (6.7%) and complicated forms (19.1%) of the disease is observed, and the growth of ascites and aplastic anemia cases in HA draws particular attention.

This review summarizes current data on the pathogenetic mechanisms of fibrosis in chronic liver diseases. Controlled inflammation and transdifferentiation of hepatic stellate cells into myofibroblasts is a key element of fibrogenesis, however, further study of the role of each of the macrophage populations is required. The initiation and progression of liver fibrosis is promoted by a complex interaction of different types of liver cells, mediated by cytokines, growth factors, miRNAs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to the pathogenesis of fibrosis. Modern experimental work has proven the role of mesenchymal stem cells in liver regeneration by inhibiting the expression of the proapoptotic BAX gene. The involution of liver fibrosis is associated with monocytes of the prorestorative phenotype LY6Clow. On in vivo models, regression of fibrosis and utilization of the extracellular matrix depot by inhibition of miRNA-221-3p of hepatocytes have been proven.

The article presents a clinical observation of severe acute hepatitis of unknown aetiology with liver transplantation in a 16-year-old child, which occurred in October 2021. Initial symptoms were abdominal pain, diarrhea. The general wellbeing of the girl did not suffer, there was no fever, no intoxication syndrome. Over the next days, she began to notice the appearance of edema on the legs, an increase in the size of the abdomen. From the 10-11th day of illness – darkening of urine, acholia of feces, jaundice were observed. She was examined by a pediatrician, a biochemical blood test was performed, according to the results the girl was hospitalized with a diagnosis of acute hepatitis. According to the severity of the condition, she was hospitalized in the ICU. On admission she complained of abdominal pain, jaundice, edema, and weakness. On examination: jaundice, scleral icterus, hemorrhagic rash at the site of the tourniquet, bleeding from injection sites, hepatomegaly, anasarca. In blood tests: progressive anemia, thrombocytopenia, increased AST (with a decrease in dynamics against the background of progression of liver failure), a decrease in total protein and albumin, fibrinogen, prothrombin according to Quick. Laboratory excluded viral hepatitis A-E. The only infectious agent diagnosed was group F adenovirus in feces. By the third day of hospitalization developed of multiple organ failure, DIC. On the 4th day of hospitalization, the child was transferred to a specialized hospital, where an emergency liver transplantation was performed. The operation was successful, the child was discharged in a stable condition.

Hepatitis B, despite of being a controlled infection today, is one of the most common form of hepatitis in the world. According to the experts' evaluation there are about 3 million patients with chronic hepatitis B in our country. The global strategy of the World Health Organization includes the elimination of viral hepatitis by 2030.The program used in the North-West Federal District to eliminate acute hepatitis B has reduced the incidence rate due to the widespread vaccination coverage of children and the annual increase in adult immunization coverage.However, the relevance of HBV-infection in children still remains high which is associated with a high infection by hepatitis B virus in women of childbearing age and the possibility of the transmission of the infection from mother to her child. In case of perinatal infection the formation of chronic hepatitis B in children reaches up to 90%. The natural course of chronic hepatitis B is characterized by a change in pathogenetically determined phases, and HBsAg-negative infection, which is a latent (occult) form of hepatitis, was added to them in 2009. Occult hepatitis B is an epidemiological danger, for the child as well, if the mother suffers from this form of chronic hepatitis B. Monitoring of pregnant women is often limited to identifying only HBsAg, which is not enough to detect occult hepatitis B. Lately diagnosed occult HBV-infection can become a source of the infection for the baby, especially in cases when due to some reasons there are disorders in hepatitis B vaccination schedule after birth. The article presents an interesting clinical case of family hepatitis B.

There is a close relationship between intestine and liver, so-called ‘gut liver’ axis, especially in patients suffered from chronic liver diseases with significant degree of fibrosis. Small intestinal bacterial overgrowth and disturbance in the microbiota composition lead to an increase in the permeability of the intestinal epithelium, the development of endotoxinemia, the activation of pro-inflammatory cytokines and, as a consequence, an additional damage to hepatocytes.Objective. To estimate the incidence of bacterial overgrowth syndrome (BOS) in the small intestine in adolescents with chronic hepatitis C (CHC), to identify the interaction between this syndrome and cytolytic activity, the degree of fibrosis.Materials and methods. There is a group of 33 patients aged 12—17 years old with CHC. All children underwent a hydrogen breath test with lactulose. The degree of fibrosis was assessed by the results of liver elastography (Fibroscan), cytolytic activity was determined by the level of alanine transaminase in serum.Results. The frequency of BOS was 81.8% in the study group. As a result of the correlation analysis, no relationship was found between the development of BOS and the degree of cytolytic activity of chronic hepatitis C (criterion χ2= 0.914, p > 0.05). Also, there was no correlation between excessive bacterial contamination and the degree of fibrosis in the liver tissue (criterion χ2= 0.914,p> 0.05).Conclusion. BOS in children with CHC occurs much more often than in adults. However, no relationship was found between this syndrome and the severity of cytolytic activity, the degree of fibrotic changes in the liver.

The aspects of virus hepatitis C immunopathogenesis are discussed. The main attention is paid to higher production of Th1 cytokines providing active protection of the host from HCV. The up-to-date approaches to the therapy of chronic hepatitis C, described in the literature and the original ones, including the triple therapy with immunomodulators of various mechanisms of action, i.e. cycloferon (injections and tablets), galavit and derinat are presented. The comparative efficacy of the therapy is estimated. Cycloferon is shown to be the drug of choice in the treatment of patients with virus hepatitis addicted to narcotics. The clinical and laboratory efficacy of the metabolic hepatoprotector remaxol with antioxidant activity is described. Its high effictivity and satisfactory tolerability (side effects requiring discontinuation of the drug use were recorded only in 0.3% of the cases), as well as the minimal risk of no biochemical remission after its use allow to conseder remaxol as a highly efficient metabolic hepatoprotector for pathogenetic therapy of chronic hepatitis.

The authors' findings and literature data on the pharmacotherapeut efficacy of cycloferon, an interferon inductor (immunomodulators) are described. The drug effect in the treatment of various socially significant children' diseases, including acute respiratory tract viral infection, bronchial asthma, allergic conditions with infection protection disturbances, mycoplasmic infection, bronchopulmonary complications of acute respiratory tract viral infection with low intensity of free radical oxidation is indicated. The use of cycloferon at the background of vaccination was shown to provide inhibition of the autoimmune processes causing postvaccinal complications in frequently ill children. The results of the use of cycloferon in the treatment of gastrointestinal tract and intestinal infections of both the viral and bacterial genesis are discussed. Cycferon is recommended to be used for correction of the intestine dysbiosis (the microflora level came to normal in 95% of the children). The use of the drug in surgical pathology and in particular in appendicular peritonitis for decreasing the postoperative complications and correction of the immune disturbances due to chronic viral hepatitis C and B in children under the complex therapy is described. The cycloferon safety and efficacy were confirmed by the postmarketing randomized trials.

The data on the efficacy of antivirals and their impact on the virologic and immunologic indices in HCV- and HBV-infected children are presented. The best therapeutic effect in the management of children with chronic virus hepatitis was provided by combined antiviral therapy of different action. In the treatment of babies the drugs of choice could be viferon or cycloferon, for the 2-year older children with chronic hepatitis B the combination of viferon + cycloferon should be recommended and for those with chronic hepatitis C the combination of interal + cycloferon could be used. The cycloferon combination with interferons-а makes it possible to generate the Th1 cellular immune response, to minimize the side effects of interferons and chemotherapeutics and to improve their tolerability. The complex therapy of patients with chronic hepatitis B and lambliasis, using cycloferon and macmiror, provided stable effect, less frequent relapses of lambliasis and minimum side effects of the specific therapy. The repeated isolation of lamblia within a 1-year observation period was recorded only in 16.6% of the children treated with cycloferon vs. the control (40.0%).

The results of clinical and laboratory examination of 107 children suffering from chronic hepatitis B or C were analysed. The biochemical criteria of the endogenous intoxication were investigated. Specific blood tests with antiviral drugs were conducted before the treatment and individual therapy schemes were assigned according to the tests' results. The early and sustained virological response rates during the individual antiviral treatment of the children with chronic hepatitis C proved to be 70.83 and 62.5% respectively.

The best therapeutic effect in the treatment of patients with chronic hepatitis B was observed with the use of cycloferon in the scheme of the antiviral therapy. The combination of cycloferon with lamivudine provided complete stable remission in 54.1% of the patients, whereas the use of а-interferon in combination with cycloferon provided remission in 44.1% of the lamivudine-resistant patients. The use of cycloferon in the therapy of chronic hepatitis B made it possible to lower the frequency and manifestation level of the side effects and prevented the lamivudine resistance development and generation of the virus mutants.

Family hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) is a rare hereditary disease, which is based on a disturbance of the regulation of the immune response, leading to proliferation and activation of histiocytes, phagocytosis of peripheral blood cells. The most common mutations include – PRF1, UNC13D, STX11. Two cases of familial hemophagocytic lymphogystyocytosis in children of an early age from a single family, features of the course are described.

The efficiency and timeliness of medical care of infectious patients are largely determined by the promptness of diagnosis and the rational organization of medical sorting of patients and contact persons. In 2016 there were 36 anthrax cases in the Yamal. In the immediate area of the epidemic were 327 people, including 135 children, in the endangered area – 539 people, including 217 children. Organization of medical care for patients and contact persons was accompanied by objective difficulties associated with the vastness of the territory under threat of infection spread, the presence of atypical and rare clinical forms of anthrax. Тhe article presents the analysis of actions for rendering of medical aid to patients with anthrax in the Yamal in 2016, and the proposed algorithms in medical triage and the organization of the emergency unit.

36 cases of human infection with anthrax, manifested in various clinical forms, were registered in the territory of Yamalo-Nenets Autonomous District in 2016. Cutaneous anthrax was characterized by emergence of carbuncle, however objective difficulties of clinical diagnostics, associated with atypicality of clinical manifestations (erysipeloid form of the disease, crusting) were outlined. Clinical manifestations of oropharyngeal anthrax were severe febrile reaction, intoxication, edema of subcutaneous fat on face and neck, and lesions of mucous membranes. Intestinal anthrax was diagnosed in one patient and characterized by the acute onset followed by faintness, loss of appetite, vomiting, and abdominal pain. Based on the results of carried out investigations, put forward were the measures on optimization of approaches to clinical diagnostics of anthrax.

We have performed primary examination of 50 children with neonatal hepatitis. Prevalence of herpes infection as the etiologic agent (40,0%) has been found, as well as parenteral hepatitis, both as an isolated (26,0%) and mixed infections. We conducted a comparative analysis of clinical and laboratory data at initial examination and determined the outcomes of neonatal hepatitis to 12 months of life depending on the etiology. Congenital CMV- etiology hepatitis characterized by more cytolysis, mainly due to aspartate aminotransferase and cholestasis, which is 33,3% of cases combined by acholia and urobiliya. In 50,0% of patients with CMV-hepatitis was detected fibrosis with a mean value of liver elastography 9,9 kPa, which is ІІІ degrees of fibrosis METAVIR scale, whereas in children with primary chronic hepatitis C and concomitant HCV + DNA-virus infection fibrosis was not registered. Despite on the large number of modern non-invasive techniques for determining the degree of hepatic fibrosis, the use of its in children during the first months of life is limited and does not allow to predict disease outcome.

This review presents the current possibilities of diagnosis of children’s liver disease: to define avidity of antibodies to hepatitis A, C for detection early infection, the development of non-invasive panel of serum markers of fibrosis and the introduction of elastography liver, as an alternative to needle biopsy. Indicated promising directions in the therapeutic tactics of viral hepatitis in children associated with the use of combined schemes of parenteral interferon (IF), including pegylated, in conjunction with similar nukleoz(t) ides, IF inducers.

We anylised results of elastography of 77 patients with chronic liver diffus lesions including: viruses hepatitis B, C, D – 50, autoimmune – 16, metabolic disease – 6, neonatal hepatities – 5 persons. Fibrosis stage was assessed on METAVIR scail. For patients with viruses hepatitis B, C with an averege duration of disease 9,8±0,7 years, a minimum fibrosis stage (F0-1) and low cytolytic activity were indicated. Patients with viruses hepatitis D were characterised by F2 fibrosis stage at the level of hyperenzemia to 4-5 rate, and history of the disease – 10,3±1,8 years. Patients with metabolic liver damage showed signs of modarate fibrosis at 10,3±1,8 years. Heavy fibrosis was marked in autoimmune hepatitis with duration of disease 5 years and indicators of ALT to 3 rate. Neonatal hepatities were characterised by the highest level of cytolysis and by development of fibrosis in 80% of cases with 0,9+0,3 year history of the disease.