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Relevance: the annual incidence of acute respiratory infections (ARI) is in the lead in the structure of infectious pathology in the Russian Federation. One of the main issues is the development of optimal strategies for prevention of these diseases in high-risk groups.Aim: to evaluate the preventive and clinical efficacy as well as safety of various dosage forms of interferon alpha-2b in relation to ARI in young adults from organized groups.Materials and methods: our study included 300 volunteers aged 18 to 20 years, 100 of them were prescribed interferon alpha-2b in the form of a gel in addition to non-specific methods for the prevention of ARVI, 100 participants received interferon alpha-2b in the form of an ointment, 100 participants did not receive antiviral drugs.Results: the use of interferon alpha-2b ointment for prevention of ARI in organized groups significantly reduced the number of people who had ARVI and cases of ARI during the observation period. Among those who used interferon alpha2b no pneumonias occurred, the duration of hospitalization was statistically significantly reduced compared to the group of volunteers who used only non-specific prophylaxis methods. Participants who received interferon alpha-2b ointment had ARVI mainly in a mild form. No adverse events that could be associated with the use of the study drug were recorded during the observation period.Conclusion: the use of interferon alpha-2b in the form of ointment showed preventive and clinical efficacy against ARI in young adults from organized groups.

Aim. To study the efficacy and safety of Riamilovir in patients diagnosed with acute respiratory viral infection using several dosage regimens of the drug.Material and Methods. The clinical efficacy and safety of Riamilovir were evaluated based on the results of a study, that included 150 patients in three comparative groups, 50 patients each. The research groups received etiotropic antiviral therapy with 1 capsule (250 mg) of Riamilovir 3 times per day for 5 days in the first group; in the second group, patients received Riamilovir off-label — 1 capsule (250 mg) 5 times per day for 5 days; and the third group included 50 patients who received only pathogenetic treatment.Results. As a result of the study, Riamilovir demonstrated a high safety profile regardless of the dosage regimen; no adverse events were registered. It was shown that Riamilovir use, regardless of the dosage regimen, led to a statistically significant reduction in the duration of inpatient treatment. It should be noted that the shortest periods of hospitalization were observed in patients who received the studied drug at increased daily dosages. Riamilovir was found to reduce the duration and severity of general infectious signs of the disease, while complete elimination of ARVI pathogens occurred by the 6th day of hospitalization; the shortest total duration of fever and a number of respiratory tract syndromes was registered among patients receiving Riamilovir at a daily dose of 1250 mg for 5 days.Conclusion. The etiotropic antiviral drug Riamilovir has shown clinical efficacy when used in both treatment regimens in patients with acute respiratory viral infections, as well as a good safety profile.

Crimean haemorrhagic fever (Crimean-Congo haemorrhagic fever) – an important public health problem due to the wide geographical spread, the ability to cause epidemic outbreaks of disease and high mortality. Evidence that human infection in some cases may occur in direct contact with the patient (bypassing the vector) indicates a high risk of contamination of surrounding people. This article presents a case of severe Crimean haemorrhagic fever in combination with tick-borne borreliosis with different clinical manifestations of the disease with many complications developed due to both direct and indirect effects of virus not only on blood cells, the system of hemostasis and vascular component with the development of hemorrhagic syndrome, but also on many organs and systems of the body. The possibility of long-term persistence of the Crimean haemorrhagic fever virus in the human body against the background of the inhibition of the immune system of the body and the severe course of the disease associated with the development of life-threatening complications, leads to a high risk of death, prolonged restorative treatment and extended hospitalization.

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.

The article describes a clinical case of atypical severe course of parvovirus B19 infection, similar in its manifestations to meningococcal infection, with combined infection with Meningococcus, Hemophilus bacillus, influenza A virus. A patient hospitalized with acute respiratory disease and toxicoderma had new symptoms within 24 hours: headache, hemorrhagic rash, decrease in blood pressure to 80/50 mm Hg, fever up to 39.8 0C. Based on the symptoms, a preliminary clinical diagnosis was made: “Meningococcal infection, generalized form – meningococcemia, severe course. Infectious-toxic shock of the 2nd degree.” During laboratory examination of clinical samples of the patient by bacteriological, serological and molecular genetic methods, there was no growth of bacterial microflora in liquor, blood and smears from the pharynx and nose. Genetic material (DNA and RNA) of Neisseria meningitides, Haemophilus influenza and influenza A/H3N2 was detected in a smear from the nasal cavity. At the same time, parvovirus B19 DNA was isolated in the patient’s cerebrospinal fluid and blood in a high viral load (Ct 21.1 and Ct 4.9, respectively). The patient was found to have not only IgG, but also IgM antibodies to parvovirus B19, which is a confirmation of acute parvovirus B19 infection. A pronounced allergic reaction was confirmed by a high index of total IgE (1068 units/ml). Thus, we have described an atypical case of laboratoryconfirmed parvovirus B19 infection in the presence of bacterial-viral mixed infection and an allergic reaction in the patient.

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19.The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relation-ship between viral load and changes in the parameters of the cellular component of the immune system.A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene. A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined.We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+).Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve early assessment of clinical condition in the patients with COVID-19. Changes in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.

The aim of the analysis was to describe the results of administration of pan-genotype antiviral therapy (glecaprevir / pibrentasvir, GLE / PIB) in real-world setting in three clinical centers in St. Petersburg within the city program for the treatment of chronic hepatitis C. Materials and methods. A retrospective analysis of the GLE / PIB usage of in the period from 2019 to 2022 within the city program for the treatment of chronic hepatitis C in St. Petersburg was carried out. Results. The analysis included 464 patients treated in three clinical centers of St. Petersburg: St. Petersburg State Medical Institution “Clinical Infectious Diseases Hospital named after S. P. Botkin”, St. Petersburg State Medical Institution “Center for the Prevention and Control of AIDS and Infectious Diseases” and the Clinic of Infectious Diseases of the Military Medical Academy named after S. M.Kirov”. Overall 452 out of 464 patients (97 %) achieved SVR12. According to the duration of treatment, SVR12 rates were the following: 8 weeks – 97.7 % (419 / 429), 12 weeks – 92.9 % (26 / 28) and 16 weeks – 100 % (7 / 7). The effectiveness according to fibrosis stage was as follows: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-A, B) – 94 % (118 / 125). SVR12 according to HCV genotypes and subtypes was the following: genotype 1b – 100 % (63 / 63), genotype 1a – 91 % (21 / 23), genotype 1 unspecified – 100 % (23 / 23), genotype 2 – 98 % (50 / 51), genotype 3 – 97 % (292 / 301). In patients with an indeterminate genotype, the efficacy was 100 % (7 / 7). Antiviral therapy was well tolerated, there were no cases of discontinuation of therapy, as well as cases of the development of serious adverse events. Conclusion. GLE / PIB has demonstrated high effectiveness in the real-world setting in patients infected with prevalent genotypes of HCV, including those with genotype 3 and compensated liver cirrhosis. The results of our analysis fully correspond to the data obtained earlier in clinical trials andreal-world setting.

Aim: to build a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Materials and methods: data from 906 medical records of patients aged 18 to 44 years with laboratory-confirmed SARS-CoV-2 infection during 2020–2021 period was analyzed. Evaluation of laboratory and instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p≤0,05. The neural network was trained using the Pytorch framework. Results: in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum iron, transferrin, and absolute peripheral blood eosinophil and lymphocyte counts were significantly higher than in patients with severe СOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood pressure in the group of patients with mild and moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and their threshold values. A model intended to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based on artificial intelligence method with high accuracy predicts the likelihood of severe SARS-CoV-2 course development in young adults.

Aim: to evaluate the efficacy and safety of convalescent plasma therapy for patients with severe SARS-CoV-2 infection.Materials and methods: the study included 64 patients with laboratory-confirmed severe new coronavirus infection. The control group consisted of 58 patients who, in addition to standard therapy, received a transfusion of plasma from donors who had recovered from COVID-19. The effectiveness of immune plasma was assessed by the duration of fever, the level of oxygen (SpO2 %) in dynamics, the detection of SARSCoV-2 RNA in nasopharyngeal and oropharyngeal swabs using PCR method in dynamics, as well as by the dynamics of blood tests results. Adverse events (any medically adverse events that occurred after immune plasma transfusion) were recorded as safety criteria.Results: patients who received convalescent plasma, showed a significantly shorter period of SARS-CoV-2 replication compared with the control group. The use of immune plasma did not have a statistically significant effect on the duration of the fever, as well as the dynamics of blood oxygenation. Also, there were no significant differences compared with the control group when assessing blood tests parameters.Conclusion: The use of COVID-19 convalescent plasma to treat severe COVID-19 did not show significant clinical effect but reduced the period of viral replication. It also showed no unexpected or serious adverse events.

An important area of effective control of the COVID-19 pandemic is the study of the pathogenetic features of SARSCoV-2 infection, including those based on the assessment of the state of the microbiota and intestinal permeability.Purpose: To study the clinical features of the new coronavirus infection (COVID-19) in patients of mild and moderate severity at the stage of hospitalization, to determine the role of intestinal permeability disorders, changes in the qualitative and quantitative composition of the microbiota in the formation of systemic inflammation in COVID-19 patients.Material and methods: The study was performed in 80 patients with COVID-19, whose average age was 45 years, 19 of them had mild and 61 had moderate severity of the disease. The scope of the examination included traditional clinical, clinical and laboratory, biochemical, instrumental and radiation studies, as well as original methods for studying microbiota and intestinal permeability.Results and conclusions: Clinical features of the course of COVID-19 were studied, clinical and biochemical features, manifestations of systemic inflammation, changes in the intestinal microbiome of patients with mild and moderate severity were identified, concentration levels of proinflammatory cytokines, insulin, fecal calprotectin and zonulin were determined, reflecting the features of intestinal permeability against the background of COVID-19. The role of intestinal permeability and microbiota as the main drivers of the development of gastroenterological manifestations of COVID-19, accompanied by a more severe course of the disease, is emphasized.

Introduction. Treatment of respiratory failure in pneumonia caused by coronavirus infection (COVID-19) is still an unsolved problem that requires a comprehensive approach and the development of new methods that expand the range of possibilities of modern therapy. There is evidence that the heated oxygenhelium mixture has a positive effect on gas exchange in the infiltration zone by improving both ventilation and diffusion.AIM of study. To evaluate the effectiveness of the inclusion of a heated oxygen-helium mixture HELIOX (70% Helium/ 30% Oxygen) in the complex intensive care of respiratory failure of pneumonia caused by SARS-CoV-2 infection.Material and methods. The study included 60 patients with confirmed viral pneumonia caused by COVID-19. The patients were randomized into two groups: group 1 (n=30) — patients who were treated with the standard COVID-19 treatment protocol with the heated oxygen-helium mixture HELIOX, and group 2 (control) (n=30) — patients who received standard therapy. Lethality was studied for 28 days, the time in days until a steady increase in SpO2>96% was achieved when breathing atmospheric air; the time until the patient is transferred from the intensive care unit (ICU) to the general department.Results. Inhalation of the HELIOX mixture (70% Helium / 30% Oxygen) resulted in a faster recovery of the hemoglobin oxygen saturation index (SpO2). Starting from day 3, these differences became statistically significant. The time in days from inclusion in the study to a persistent increase in the degree of oxygen saturation of hemoglobin (SpO2>96%) when breathing atmospheric air in the group with inhalation of the HELIOX mixture was less — 8 (7; 10), compared to 10 (8;13) in the control group (p=0.006). In the group with inhaled HELIOX mixture, the median treatment time in the ICU was 8 (7; 9.5) days vs 13 (8; 17) days (p

Given that COVID-19 is a global public health problem and that almost all countries in the world have been severely affected by the COVID-19 pandemic, research is being actively pursued to better understand the effects of the virus on human cells. However, it is not clear what changes are observed in the cells of the main gate of infection – the mucosa of the mouth and the nose at different clinical forms and at different periods of disease. Understanding the ultra-structural cell changes of SARS-CoV-2 targets may help clarify the pathogenic aspects of infection in the lower respiratory tract. In this study, the elements of the life cycle of SARS-CoV-2 virus in the cells of the respiratory epithelium of the nose in patients with COVID-19 were evaluated using electron microscopy for the purpose of detecting the peculiarities of viral activity depending on the form and period of disease. Bioptats of the nasal mucous membrane were taken from COVID-19 patients and subsequently examined by electron microscopy. The severity of structural changes in tissue samples, presence of SARSCoV-2 virus in cells were determined, then bioptats were grouped according to the clinical form of the infection process (inapparent, acute upper respiratory tract infections, viral lung disease) and period of disease. It has been established that the most characteristic changes in the mucous membrane of the nose were observed in the first week of infection caused by SARS-CoV-2 and occurring in the form of acute respiratory disease, while viral lung infections have had the highest virus density in vesicles within cells, the formation of smooth virus-free vesicles is most common in inapparent forms. The data obtained may indicate that the formation of classical virus-induced changes in the respiratory epithelium of the nose mucous (vesicles with viral particles and signs of their release from the cell) is characteristic of localized forms of infection caused by SARS-CoV-2 (respiratory infection of the upper respiratory tract) and in cases of generalized infection (viral infection of the lungs and probably other organs and systems) accumulation of the infectious agent in high concentrations in vesicles.

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

Aim. The study evaluates clinical effectiveness and safety of etiotropic antiviral medications with a direct mechanism of action (Riamilovir, Ribavirin, Umifenovir) for the treatment of moderate SARS-CoV-2 infection in adults. Materials and methods. The study used the data from 59 health records of patients with moderate PCR-confirmed SARS-CoV-2 infection. Control group included 29 patients treated with 1250 mg Riamilovir off-label per day for 5 days (250 mg 5 times a day), comparison group consisted of 30 patients, who received 800 mg Ribavirin and Umifenovir per day for 5 days. The effectiveness of the medications was assessed by the duration and severity of general infectious and respiratory syndromes, anosmia and ageusia, as well as the oxygen content in the blood, the timing of SARS-COV-2 virus elimination from the body according to the results of control studies of nasopharyngeal swabs using the PCR method and dynamics of blood tests results. Results. A statistically significant decrease in the duration of fever, cough, and anosmia and a more rapid elimination of the virus from the body were noted in the group of patients receiving Riamilovir. Decreased levels of non-specific inflammatory markers in blood serum, as well as normal values of liver enzymes were observed in control group during therapy, as opposed to the comparison group. No serious adverse events were noted when using the medication. Conclusion. Nucleoside analogue medication Riamilovir showed good effectiveness and safety profile in adult patients with moderate SARS-CoV-2 infection.

Aim. To evaluate the antifibrotic effect of bicyclol with promising clinical effects on diffuse parenchymal liver diseases.Materials and methods: We have included 40 adult male Wistar rats (weight, 180 to 200g) with experimentally inducted toxic F3 stage liver fibrosis. Control group consisted of 16 rats that received standart chow, experimental group of 24 rats also received 30-day bicyclol supply. To evaluate the results we used histological, biochemical, molecular genetic and statistical methods.Results. In experimental group interlobular fibrosis was maintained in 4,16% (p

Aim. In this study we evaluated clinical effectiveness and safety of nebulized prostacyclin in patients with Novel Coronavirus Disease (SARS-CoV-2). Materials and methods: We have included 44 male patients with moderate PCR confirmed SARS-CoV-2 infection in this study. Control group consisted of 23 patients treated with nebulized prostacyclin (PGI2). besides standard therapy. We compared intensiveness and duration of infectious intoxication syndrome, duration of fever, cough as well as SpO2 level, complete blood count and chemokine status values. Results: Statistically significant difference in duration of fever, cough, intensiveness and duration of infectious intoxication syndrome were observed. Lymphocyte and platelet counts were significantly higher in control group We have also noticed significantly lower level of proinflammatory mediators and C4-complement component in control group. Only 1 adverse effect associated with inhaled prostacyclin was reported. Conclusion. Nebulized prostacyclin showed therapeutic efficacy and good safety profile in adults with moderate COVID-19.

The article describes action of the Infectious Diseases Service of the Armed Forces in national biosecurity control through leveraging experience of military involvement, emergencies, infectious epidemic outbreaks, including rescue measures rendered during the SARS-CoV-2 pandemic.We utilise experience of military infectiologists to exemplify medical care management under admission influx of contagious patients. Principles are clarified of early clinical diagnostics of potentially pandemic infectious diseases and early active detection, isolation, sorting and evacuation of contagious patients in martial and close field conditions. Besides, specifics of providing specialised medical care to contagious patients, including preventive intensive care, is detailed.In 2020, healthcare and legal authorities worldwide recognised the critical capability to act under conditions close to real combat and so satisfy a minimum qualification standard of a military doctor, including infectiologist’s skills, at both systemic and individual levels of infection control, regardless of primary medical specialty. From this perspective, expertise of the Chair of Infectious Diseases (with training in medical parasitology and tropical diseases) of the Military Medical Academy can be an asset both in practice and teaching in medical universities country-wide.

Meningococcal infection is an acute infectious disease caused by Neisseria meningitidis, characterized by a polymorphism of clinical manifestations from meningococcus carriage to invasive forms. They, in turn, pose a great danger to the patient’s life, since in most cases they have a severe course with the development of complications, fulminant course and high mortality. The success of treatment of invasive meningococcal disease largely depends on the timeliness of diagnosis and the timing of treatment initiation. The article describes a clinical case of a generalized form of severe meningococcal infection with a rapidly developing infectious toxic shock, disseminated intravascular coagulation syndrome in a soldier who had previously refused specific prophylaxis. Despite the mistakes made at the prehospital stage and, accordingly, late hospitalization, this case had a favorable outcome.

The aim of the study was to assess the possibilities of noninvasive diagnosis of liver fibrosis (FIB-4 and APRI indices) in patients with CHC and abdominal obesity.Materials and methods. 52 men with CHC were examined. Genotype 1 was determined in 24 patients, genotype 3 in 19 patients and genotype 2 in 9 patients. According to the severity of fibrosis, patients with CHC were divided: without fibrosis (F0) - 12 patients, with weak fibrosis (F1) - 17 patients, with moderate fibrosis (F2) - 10 patients, with severe fibrosis (F3) - 8 patients, cirrhosis of the liver (F4) was detected in 5 patients. According to a liver biopsy, steatosis was found in 18 patients with CHC. Abdominal obesity was found in 34 patients with CHC. Non-invasive diagnosis of liver fibrosis was assessed using routine FIB-4 and APRI indices. The interval of values of FIB-4 and APRI, not related to the criteria for assessing the stage of fibrosis F3 and F4, we have conventionally designated as the «gray zone». The presence of insulin resistance was evaluated at HOMA-IR> 2.Results. Key values of the FIB-4 index in patients with CHC and abdominal obesity were found significantly more often than when calculating the APRI index. Insulin resistance in patients with CHC and abdominal obesity was statistically significantly more frequent than in patients with CHC and without abdominal obesity. At stages F3-F4 in patients with CHC, abdominal obesity and insulin resistance, APRI values were recorded more often in the «gray zone»than FIB-4 values.Conclusion. The FIB-4, APRI, HOMA-IR indices can be used in patients with CHC and abdominal obesity during the follow-up and dynamic monitoring of patients with CHC to highlight risk groups. FIB-4 was significantly more informative for determining the stage of fibrosis than APRI in patients with CHC and abdominal obesity with insulin resistance (HOMA-IR> 2).

Herpes viruses are widespread in the human population, they are able to infect almost all organs and systems of the body. Currently, 8 serotypes of herpesviruses pathogenic for humans are known: herpes simplex viruses of the 1st and 2nd. type, chickenpox — herpes zoster, cytomegalovirus, Epstein-Barr virus, 6th, 7th and 8th human herpes viruses. Primary infection with herpes viruses in 60—90% of cases occurs in early childhood, and, as a rule, is not accompanied, by typical clinical manifestations. Due to the lack of mandatory registration of the incidence of herpes virus infections in our country, the true number of patients is unknown. It is believed that about 20 million people are infected, every year in Russia and. the CIS countries. Herpes viruses, to a greater or lesser extent, can be considered, hepatotropic. A large number of studies are devoted, to the problem, of cytomegalovirus infection, one of the manifestations of which, is hepatitis. Most often, cytomegalovirus hepatitis occurs in immunocompromised. individuals or in patients receiving immunosuppressive therapy, cases of cytomegalovirus hepatitis and in immunocompetent individuals are also described. With liver transplantation without antiviral therapy, cytomegalovirus infection manifests itself in 11-28,5% of recipients and. can lead, to the development of liver failure, loss of transplant and. death, of the recipient. Performing diagnostic studies using both, serological and. molecular biological methods at different periods after liver transplantation, allows to detect cytomegalovirus infection timely and. initiate treatment, thereby avoiding graft rejection and. the death, of the recipient.

Aim. To estimate the distribution of genotypes and subgenotypes of the hepatitis B virus among military personnel with chronic viral hepatitis B. Materials and methods. The work used samples of blood plasma and biopsy material obtained from 90 active or retired military personnel with chronic viral hepatitis B with various degrees of fibrosis undergoing treatment in St. Petersburg. Primary detection of HBV was carried out by isolating nucleic acids (NK) from the blood plasma using the «AmplePrime Ribo-prep» commercial kit (FBIS CRIE, Moscow). Specific primers were used for the amplification and sequencing reaction. Overlapping primer pairs were used, jointly flanking 1475 base pairs (bp) fragment, including the recommended for HBV genotyping the 1169 bp Pre-S1/Pre-S2/S. Results. Among 90 samples from patients with chronic viral hepatitis B from different regions of the Russian Federation, HBV subgenotypes are represented in the following ratios: D2 = 45.6% (n=41), D1 = 32.2% (n=29), D3 = 13.3% (n=12), A2 = 6.7% (n=6), D4 and A1 by 1.1%, respectively. The distribution of HBV subgenotypes from the North Caucasian federal district (D1 – 63.6%, D2, D3, D4, A2 – by 9.1%) was significantly different from the distribution among patients from the Central and North-Western federal districts (D1-20, 9%, D2 – 58%, D3 – 16.3%, A2 – 4.8%) (χ2=11,9 при p=0,0076, df=3). Uncharacteristic for the Russian Federation subgenotypes D4 and A1, representing single imported cases. The tendency to shift the distribution of genovariants due to imports of the corresponding HBV subgenotypes from other countries, including the Central Asian countries, is discussed. Conclusion. A systematic study of the HBV isolates phylogeny provides new information about the HBV subgenotypes distribution among certain population groups, including military personnel.

Background and aims: to estimate concentration of sMadCAM-1 in peripheral blood at patients with chronic hepatitis C with excess body weight.Materials and methods: The research included 88 patients (67 men, 21 women 41.4±3.2 years of age) with chronic hepatitis C (CHC) and excess body weight (the index of body mass is ³25 kg/m2, and abdominal circumference more than 94 cm in men, and 80 cm in women) with various morfofunktsionalny changes in a liver and a small bowel. From them men there were 67 people, women – 21, middle age was 41.4±3.2 years.To all the patients complex clinical, biochemical, virologic, morphological trial was carried out. The functional condition of intestines was estimated by identification of a small intestinal bacterial overgrowth (SIBO) when carrying out the hydrogen respiratory test (HRT) with lactulose and existence of endoscopic signs of inflammation of a mucous membrane of intestines at a fibroezofagogastroduodenoskopiya. The quantitative assessment of a mucosal addressin cell adhesion molecule -1 was carried out by the definition concentration of its soluble form (sMadCAM-1) in a blood plasma by enzyme immunoassay method.Results: the sMadCAM-1 level of peripheral blood at the patients with excess body weight increased in process of progressing of a stage of chronic hepatitis C (F0 – 349.10 (324.27-373.92) ng/ml; F1/2 – 439.69 (406.43-472.94) ng/ml; F3/4 – 1057.82 (593.38-1522.26) ng/ml; p˂0.05), existence of a syndrome of excess bacterial growth and endoscopic signsof a duodenitis. Besides, patients had its concentration more with the biochemical signs characterizing cytolytic (at ALT˃N: 502.54 (432.04-573.03) ng/ml against 381.04(345.49-416.58) at the ALT normal values), cholestatic (at GGTP˃N: 550.59 (453.31-647.88) ng/ml against 400.86(365.13-436.59) atnormal GGTP, p values 0.05; at ALP N: 572.2 (353.7-790.8) ng/ml against 468.7 (408.5-528.9) ng/ml at normal ALP, p values 0.05) and metabolic syndromes (at glucose of blood, TG, VLDL N: 562.93 (369.59-756.27) ng/ml, 681.15 (387.81-974.49) ng/ml, 809.65(124.04-1495.28) against (438.34(391.36-485.31) ng/ml), (421.69(379.41-463.97) ng/ml), 434.47(389.45-479.48), p values 0.05 at normal values of these indicators respectively). Conclusion: Progressing of fibrosis and functional disturbances in intestines are interconnected with increase in concentration of MadCAM-1 in blood that allows to consider pathological changes in intestines of various genesis as the accessory factor promoting progressing of СHC at patients with excess body weight. Besides, definition of concentration of sMadCAM-1 in peripheral blood can be used as one of markers of noninvasive diagnostics of a stage of fibrosis at the patients with СHC and excess body weight.

Chronic hepatitis C remains one of the most important socially significant infections for world health. The use of modern highly effective drugs with direct antiviral action allows to achieve a sustained virological response in patients. At the same time, in a significant number of cases after elimination of HCV infection, the progression of fibrosis continues with the development of its terminal stages and an unfavorable outcome for patients. The article focuses on comorbid pathology, which is a leading factor in this process in patients with chronic hepatitis C who have achieved a sustained virological response and presenting a serious challenge to modern hepatology.

Aim. Study of efficacy and safety of ribavirin in combination to pegylated interferon α-2a (PegIFN- α-2a) within combined mode of treatment of patients with chronic hepatitis C (CHC) including patients with compensated cirrhosis and and HIV coinfection were conducted. Material and methods. Two open prospective multicenter, non-comparative clinical trials ML16709 NCT00922779 and ML27851 «Standart» (NCT01609049) were conducted. 6661 and 1496 patients with CHC were included accordingly. All were administrated combined therapy: ribavirin and PegIFN- α-2a. Patients with HCV genotype 1 received prescribing treatment for at least 12 but not more than 48 weeks, patients with HCV genotypes 2 and 3 – for at least 12 but not more than 24 weeks. The efficacy analysis included determining the frequency of achieving a rapid virologic response (BVO), an early virologic response (RVO), a virologic response at the end of therapy, and a sustained virologic response (SVR). The safety endpoints were assessed on data of all adverse events (AEs), serious adverse events (SNP), and clinical laboratory findings. Results. At 24 weeks SVR frequency was 43.4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 72,0% in the ML27851 study; 58,9% and 89,3% in the subgroup of patients with HCV genotypes 2 and 3 accordingly. In the ML27851 study proportion of patients with BVO was 46,8% in patients with HCV genotype 1 and 86,0% in patients with a different HCV genotype. RVO frequency was 37,4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 90,1% in the ML27851 study; 79,7% and 97,4% in a subgroup of patients with HCV genotypes 2 and 3 accordingly. The proportion of patients with virologic response at the end of therapy was 44,6% in the ML16709 study and 86.7% in the ML27851 study; in a subgroup of patients with genotypes 2 and 3, 73.8% and 97.6%, accordingly. In the ML16709 study 5887 AEs were registered, including 5812 (99%) of non-serious AEs and 75 serious AEs. In the ML27851 study 2557 non-serious AEs occurred in 822 (54.95%) patients. 49 serious AEs were registered in 39 patients (2.6%). Conclusion. The results of studies ML16709 and ML27851 confirm the efficacy and safety of treatment with ribavirin plus peginterferon alfa-2a in patients with chronic hepatitis C. The registered AEs profile is representative of pegylated interferons and ribavirin combination.

Objective: To evaluate relationships between virological and morphological data in patients with chronic hepatitis B in phase immune control and reactivation.Materials and methods: The study involved 46 patients with chronic hepatitis B, indicators defined were content of surface antigen and hepatitis B virus DNA in the peripheral blood, the level of covalently closed circular HBV DNA in liver tissue and fibrosis stage and histological activity index (METAVIR).Results: The study found a direct correlation between the level of covalently closed circular DNA in liver puncture biopsies (number of copies per cell) and quantitative content of HBsAg in serum (r = 0,51, p = 0,03) in patients with chronic hepatitis B in phase immune control. Also in the immune control phase a direct correlation between the HBV DNA and the level of HBsAg in serum (r = 0.79, p = 0.0001) is shown. The level of covalently closed circular HBV DNA in liver puncture biopsy specimens did not differ in patients with chronic hepatitis B in the phase of immune control in the phase of reactivation (1,02 ± 0,01 copies / cell and 1,03 ± 0,03 copies / cell, p = 0.72). The index of histological activity and fibrosis were not correlated with any of the investigated virological indicator.Conclusion: Results of the study emphasized the complexity and ambiguity of the relationships between both virological and morphological indicators in patients with chronic hepatitis B, determined the direction for further study (in particular the assessment of the epigenetic regulation of the synthesis of circular covalently closed DNA), as well as set the stage for improving the principles of dynamic observing the patients with chronic hepatitis B in a phase of immune control.

For the purpose of clinical laboratory and virologic characteristics of chronic HCV-infection, depending on the gene polymorphisms of IL-28B were examined 104patients. In 70 patients (50 – with genotype 1 and 20 – with genotypes 2 and 3) treated with pegylated interferon-α2a (PIFN) and ribavirin (RBV), evaluated the frequency of sustained virologic response (SVR). According to the results of the study it was found that the patients with HCV had a sufficiently high frequency of registration of «favorable» prognostic single nucleotide polymorphisms (SNPs) rs12979860 CC (23.1%) and rs8099917 TT gene IL-28B (50,9%). On therapy of PIFN and RBV SVR frequency rate in patients with chronic hepatitis C (genotype 1)and SNPs CC rs12979860 (82,4%) was significantly higher than the efficiency of treatment in patients without this polymorphism (45,5%). In chronic HCV-infection (genotypes 2 and 3) SVR was observed significantly more frequently in patients who have both IL28B CC polymorphism rs12979860, and TT for rs8099917 (88,8%).

The aim of this research is the study of the dynamics of the content of leukocytes and neutrophils in the blood of patients with chronic hepatitis C combination therapy against standard or pegylated interferon combined with ribavirin. Before treatment, as well as at different stages of combination antiviral therapy were studied absolute numbers of leukocytes and blood neutrophils in patients with CHC. In addition, studied the relationship between the dynamics of the content of white blood cells and blood neutrophils and the initial clinical and laboratory parameters (gender, age, body mass index (BMI), the genotype of the virus, the level of viremia, initial level of leukocytes and neutrophils, ALT, histological activity index, the degree of fibrosis) and option of combination therapy. Showing that the reduction of leukocytes and neutrophils have been observed from the second week of treatment, regardless of the option of combination therapy. Application PIFN-α-2а caused significantly more pronounced leukopenia and neutropenia compared with a simple treatment of IFN-α-2а. Furthermore, the development of neutropenia associated with the achievement of sustained virological response in both antiviral schemes therapy. Also we onsider prognostic criteria, indicating the possible development of severe leuco-and neutropenia during treatment: age older than 45 years, the high initial activity of replicative virus (>800 000 IU / ml).

In order to study the effect of combination antiviral therapy for hemoglobin and red blood cells in patients with chronic hepatitis C were estimated absolute numbers of red blood parameters. To determine the relation between the content of red blood cells and hemoglobin at different stages of antiviral therapy with the initial clinical and laboratory parameters (gender, age, body mass index, genotype, level of viremia, ALT, fibrosis), as well as the results of combined antiviral therapy. Established that the decrease in hemoglobin levels were observed more frequently than the decline in the number of erythrocytes (63,6% and 21,1% respectively). In addition, anemia that occurred during treatment of HCV patients with pegylated interferon-α, directly correlated with the rate of sustained virological response. The study established prognostic criteria, indicating the possible development of anemia in the background of anti-viral therapy: the female sex, BMI

Based on the survey results in 1322 patients found that patients with hronic viral hepatitis (CVH) blastocysts are found more often than in the group of individuals without concomitant pathology of the hepatic-biliary system (28.8% vs. 5.5%, respectively). In healthy individuals the blastocyst revealed more often in the summer, peaking in July and August, while in patients with CVH Blastocystis most frequently observed in winter. The high incidence of Blastocystis sp. CVH patients suggests that the pathology of the hepatic-biliary system fosters a supportive environment in the gastrointestinal tract for the colonization of its blastocyst. Molecular biological methods of investigation revealed that the subtype antroponozny blastocysts met in this population, 5.3 times less likely than those without concomitant liver disease.

In order to estimate the frequency of detection of bacterial overgrowth syndrome in patients with chronic hepatitis C, find a possible relationship between development dysbiotic changes in the small intestine and over chronic hepatitis C were examined 80 patients (68 males and 12 females). In addition to standard laboratory tests for all patients was performed hydrogen breath test with a load of lactulose and fibrogastroduodenoscopy and hepatic biopsy with subsequent histological examination of biopsy. It was found that bacterial overgrowth syndrome, according to the hydrogen breath test detected 40% of patients with chronic hepatitis C, and the severity of it increases with the progression of the pathological process in the liver tissue. urthermore, in patients with endoscopic signs of catarrhal duodenitis according fibrogastroduodenoscopy, the level of molecular hydrogen when the hydrogen breath test at the appropriate stages of measurement was significantly lower, which may be due to the lack of saccharolytic and / or the predominance of proteolytic flora in the development of bacterial overgrowth syndrome.

Intensive care of patients with infectious diseases, as part of the resuscitation, in our country took root in clinical practice on stages – from the treatment of very severe forms of some infections (nosological approach) to differentiated treatment depending on the clinical and pathogenic syndromes critical states (internosological approach). Based on the analysis of intensive therapy in 1387 patients with various infections identified the main syndromes of critical states: infectious and toxic encephalopathy, toxic shock, dehydration syndrome (shock), acute respiratory, hepatic and renal failure. Shows the frequency of their development or threat for the most common diseases. In modern conditions, improve the efficiency of treatment of patients with extremely severe forms of infectious diseases can be achieved by preventive measures – preventive intensive therapy in the presence of high-risk factors, urgent and emergency measures in the infectious disease department at the methodological and direct participation of resuscitation services, the introduction of high-tech methods and means of treatment.

The purpose of this research is the study of the dynamics of platelet count in blood of patients with chronic hepatitis C on the background of the combined antiviral therapy with standard or pegylated interferon-α in combination with ribavirin. Prior to treatment, as well as at different stages of combined antiviral therapy were studied absolute numbers of blood platelets in patients with chronic hepatitis C. We determined the relationship between platelet counts at different stages of antiviral therapy and baseline clinical and laboratory parameters (age, sex, body mass index, genotype, level of viremia, ALT, fibrosis), as well as alternative combination therapy. It is established that the significant decrease in platelet count in patients with chronic hepatitis C were observed as during treatment with pegylated or standard interferon-α in combination with ribavirin (38,5% and 16,0%, respectively, p < 0,05). Therapy with pegylated interferon-α treatment as compared with standard interferon-α was accompanied by a more pronounced decrease in platelets, peaking at 8 weeks of treatment (188,4±3,9×109/l). In addition, we observed a direct correlation between the level of blood platelets and rate of sustained virologic response. The study identified prognostic criteria, indicating the possible development of thrombocytopenia on the background of antiviral therapy: BMI < 20kg/m2, age over 45 years.

In 125 patients with liver cirrhosis of different etiologies, classes A, B and C according to the Child-Pugh, with minimal hepatic encephalopathy and overt encephalopathy to II grade according to the West Haven criteria, we studied the efficacy of treatment of hepatic encephalopathy drugs of different pharmacological groups. The highest efficiency was found in the treatment with Stimol, treatment with probiotics and treatment included the combination of probiotics with metronidazole. Treatment with these drugs showed improvement in clinical status and in psychometric (cognitive) performance, as well as positive changes in clinical and biochemical parameters of blood. Also, this treatment was associated with the improving the quality of life of patients.

In article presents modern system of medical care to servicemen with chronic viral hepatitis. Also presented comparative analysis of the specialized care for these patients up to 2010 (prior to deployment in the clinic of infectious diseases of the Military Medical Academy center for the treatment of chronic viral hepatitis) and after. Shows that from 2007 to 2009. proportion of chronic viral hepatitis in the structure of all infectious diseases in the Armed Forces increased (in 2007 – 2.1%, in 2008 – 2.3%, in 2009 – 2.5%). Particularly significant increased incidence of contract servicemen. In 2007 – 5.2%, 2008 – 5.8% 2009 6 -%). Since 2010 there has been a strong tendency to reduce the incidence of chronic viral hepatitis in the structure of infectious diseases in general: 1.2% – in 2010, 0.8% – in 2011, and contract servicemen in particular: 4% – in 2010, 2.8% – in 2011, In addition, the article described in detail the steps and the amount of medical care for these patients.

Presented clinical case describes elimination followed by seroconversion HBsAg / HBsAb patient with HBeAg-negative chronic hepatitis B on antiviral therapy with pegylated interferon α2-a and achieving sustained virological response.

Purpose of the present research studying dynamics of the parameters describing a metabolism of iron at chronic hepatitis С patients on a combined antiviral therapy peg-interferon-2а and ribavirin. Has served 50 patients chronic hepatitis C (anti-HCV “+”, РНК HCV “+”, 1b genotype) in the age from 18 till 59 years, on the average 33±1,5years, at various stages of disease and stages of monitoring antiviral treatments. To patients the parameters describing a metabolism of iron (serum iron, transferrin, ferritin, haptoglobin, ceruplasmin, total iron binding capacity, transferrin saturation by iron were defined. The sustain virology response (SVR) was estimated - definition RNA HCV in half a year after end of treatment (72 week). It was carried out liver biopsy with the subsequent estimation of a degree of inflammatory activity and fibrosis on system METAVIR. Therapy peg-interferon-2а and ribavirin was accompanied by decrease serum iron, transferrin, ferritin, ceruplasmin, haptoglobin, transferrin saturation by iron irrespective of the answer to treatment. Thus, SVR directly correlated with higher level of iron and ceruplasmin of blood before therapy, on its background and during supervision. Normalization of biochemical activity chronic hepatitis C and positive morphological dynamics correspond with the parameters describing changes in a metabolism of iron at its patients, possibly, were compensatory-adaptive and to some extent endogen antiviral reaction of an organism of the person on HCV - infection.

In the review is presented evolution of sights on treatment of patients with chronic hepatitises since 70-th years of XX century to the present days. Stages of development of therapy sick of chronic hepatitises В, С and D are consistently characterised. The basic emphasis is made on acurrent state of a problem and the prospects opening before researchers. Algorithms of treatment of patients with chronichepatitises are presented.