Введение. Вирусы гриппа представляют серьезную угрозу для здоровья населения Земли, вызывая сезонные эпидемии и эпизодические пандемии, которые приводят к высокой заболеваемости и летальным исходам. Грипп является заболеванием, для которого разработаны противовирусные средства с доказанной клинической эффективностью. Цель. Охарактеризовать разнообразие типов/субтипов вирусов гриппа, циркулирующих в эпидемический подъем заболеваемости в сезоны 2015–2016 и 2022–2023 гг., а также оценить эффективность и безопасность препарата осельтамивир. Материалы и методы. Проведен анализ данных пациентов, проходивших лечение в СПб ГБУЗ «КИБ им. С.П. Боткина», с диагнозом «грипп» (n=159) в период 2014–2015 гг. в 2 группах: пациенты, получавшие (группа 1, n=105) и не получавшие (группа 2, n=54) осельтамивир, – и показана эффективность препарата. Для сравнения данных применяли U-критерий Манна – Уитни, р≤0,05. Результаты. Грипп А (H1N1) выявлен у 42% пациентов (n=67), грипп А (H3N2) – у 31% (n=49), грипп B – у 20% (n=32). Температура на 3–5-й день чаще снижалась в группе принимавших осельтамивир (1-я группа – Ме 36,8(Q1/Q3; 36,4/38,2) в 1,1 раза меньше, чем во 2-й группе, – Ме 38,5(Q1/Q3; 37,2/38,8)), р=0,04. Лихорадка в 1-й группе составила 6,7±2,8 дня, что было в 1,4 раза меньше, чем во 2-й группе – 9,4±4,8 дня, р=0,034. В 1-й группе к 3–5-му дню чаще снижалась частота возникновения тошноты, слабости и ознобов: р=0,04, р=0,007 и р=0,05 соответственно. Заключение. В период подъема заболеваемости гриппом в 2014–2015 гг. в этиологической структуре преобладали субтипы А(H1N1), А(H3N2), В. Несмотря на тип вируса, препарат осельтамивир показал высокую эффективность и безопасность. В настоящее время осельтамивир является единственным лицензированным препаратом, доступным для всех возрастов, который применяется для лечения пациентов с подтвержденным гриппом. Introduction. Influenza viruses pose a serious threat to the health of the world’s population, causing seasonal epidemics and episodic pandemics that lead to high morbidity and mortality. Influenza is a disease for which antiviral agents have been developed with proven clinical efficacy. Purpose. To characterize the variety of types/subtypes of influenza viruses circulating during the epidemic rise in 2015–2016 years and 2022–2023 years as to evaluate the efficacy and safety of oseltamivir. Materials and Methods. An analysis of the data was performed of patients, that were treated in St. Petersburg Clinical Infectious Disease Hospital named after S. P. Botkin with a diagnosis of Influenza (n=159) in 2014–2015 years. The patients were spitted into two groups: patients who received (1st group n=105) and did not receive (2nd group n=54) oseltamivir. The effectiveness of the drug was shown. To compare the data, the Mann – Whitney U-test was used p≤0.05. Results. The influenza A (H1N1) was found in 42% (n=67), influenza A (H3N2) in 31% (n=49) and influenza B in 20% (n=32) of patients. Body temperature on 3–5 days decreased in the group taking oseltamivir (1st group – Me 36.8 (Q1/Q3; 36.4/38.2) 1.1 times less than in 2nd group Me 38.5 (Q1/Q3; 37.2/38.8)), p=0.04. Fever duration in group 1 was 6.7±2.8 days, which was 1.4 times less than in 2nd group – 9.4±4.8 days, p=0.034. In the first group of patients, by the 3rd–5th day, the incidence of nausea, weakness and chills more often decreased, p=0.04, p=0.007 and p=0.05. Conclusion. During the seasonal rise of the influenza incidence of 2014–2015 years in the etiological structure of influenza in patients’ subtypes A (H1N1), A (H3N2), B prevailed. Despite the type of virus, oseltamivir showed high efficacy and safety. Currently, oseltamivir is the only licensed drug available for all ages to be used for the treatment of patients with confirmed influenza.

Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.

The aim of the study was to compare the clinical efficacy and safety of two antiviral therapy medications that suppress viral replication (viral RNA polymerase inhibitors) in the treatment of patients with COVID-19: favipiravir and riamilovir.Material and methods. Clinical efficacy and safety were assessed based on a retrospective study of 1071 patients, including 561 patients who received favipiravir and 510 patients who received riamilovir.Results. A statistically significant reduction in the duration of symptoms and average hospital days was recorded among patients who received ramilovir in both moderate and severe forms of the disease compared with the group that received favipiravir. Inflammatory markers (CRP, fibrinogen) decreased faster in the riamilovir group.Conclusion. Riamilovir has demonstrated higher levels of clinical efficacy and safety in the treatment of COVID-19 compared to favipiravir.

Chronic hepatitis C (CHC) represents a significant public health concern. In the majority of cases, the infection progresses to a chronic form, which is characterised by the development of fibrosis and cirrhosis of the liver. A plethora of cytokines and chemokines are generated as a consequence of inflammatory processes within the liver. These can exert a dual effect, both protective and damaging, particularly in relation to the death of hepatocytes and the progression of liver fibrosis. Furthermore, a number of growth factors have been identified as playing a role in the pathogenesis of CHC. The objective of the study was a comprehensive evaluation of a wide range of cytokines, chemokines and growth factors in the blood plasma of patients with CHC at varying stages of liver fibrosis. The study cohort comprised 63 patients diagnosed with CHC, who were divided into three groups according to the stage of liver fibrosis. The control group comprised healthy individuals (n = 32). Concentrations of the following cytokines were determined in plasma: Interleukins and some cytokines (IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17-E/IL-25, IL-17F, IL-18, IL-27, IFNα, IFNγ, TNFα, TNFβ); chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine) and growth factors (EGF, FGF-2, Flt-3L, G-CSF, M-CSF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF-A) by multiplex analysis based on xMAP technology. Nonparametric statistics methods were used for statistical analysis. As a result of the study, increased concentrations of cytokines IL-12 (p40), IL-15, IL-17E/IL-25, IL-27, IFNγ, TNFα, chemokines CXCL9/MIG and CXCL-10/IP-10 and growth factors FGF-2 and M-CSF were found at all stages of liver fibrosis. Elevated concentrations of cytokines IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-17F, IFNα, TNFβ, chemokines CCL2/MCP-1, CCL11/Eotaxin, CCL22/MDC and growth factors G-CSF, TGF-α, Flt-3L were found in severe liver fibrosis/cirrhosis. Correlation analysis revealed a relationship of high significance between the severity of liver fibrosis and the content of cytokines IL-6, IFNγ, TNFα, IL-7, chemokines CCL2/MCP-1, CCL11/Eotaxin, CXCL9/MIG, CXCL10/IP-10, CXCL1/GROα, growth factors TGF-α, PDGF-AA, PDGF-AB/BB. Thus, a certain profile of cytokines characteristic for CHC was revealed, cytokines, chemokines and growth factors significant for liver fibrosis in CHC were found.

Введение. Острые респираторные вирусные инфекции – это патология, которая чаще всего встречается в амбулаторной терапевтической практике (около 40 млн случаев в год). Термин «острая респираторная вирусная инфекция» является собирательным понятием и обозначает группу заболеваний вирусной этиологии с преимущественным поражением дыхательных путей. Общие эпидемиологические особенности возбудителей острых респираторных вирусных инфекций заключаются в единых путях передачи: воздушно-капельном и посредством контакта с зараженными предметами. Причины острых респираторных вирусных инфекций могут быть разными, однако у них есть общие эпидемиологические и клинические особенности, которые определяют единую стратегию лечения и профилактики. Результаты. Терапия острых респираторных вирусных инфекций направлена на снижение тяжести симптомов, предотвращение прогрессирования заболевания и достижение полного и стойкого выздоровления. Лабораторная этиологическая диагностика на амбулаторном этапе проводится молекулярно-генетическими методами только в отношении гриппа А и В, а также COVID-19; для идентификации других возбудителей острых респираторных вирусных инфекций ее проведение целесообразно только по клинико-эпидемиологическим показаниям, поскольку полученные результаты не влияют на дальнейшую тактику ведения пациента. Обязательным компонентом лечения является немедикаментозная терапия, включающая в себя постельный режим, диету и обильное питье. Медикаментозное лечение острых респираторных вирусных инфекций и гриппа включает этиотропные препараты, средства патогенетической и симптоматической терапии. В качестве этиотропной терапии применяют противовирусные препараты прямого и непрямого действия. Ингибиторы нейраминидазы, как и ингибиторы кэп-зависимой эндонуклеазы, используются в терапии гриппа А и В и, к сожалению, не активны в отношении других возбудителей острых респираторных вирусных инфекций. В связи с отсутствием препаратов прямого противовирусного действия, активных в отношении возбудителей острых респираторных вирусных инфекций, основными этиотропными препаратами выступают препараты непрямого (иммуномодулирующего) действия, обладающие широким противовирусным спектром, к которым, в частности, относятся индукторы интерферона. Заключение. В статье представлен анализ литературы на тему оптимизации терапии острых респираторных вирусных инфекций и гриппа в амбулаторных условиях за счет применения препаратов группы индукторов интерферона. В результате проведенного анализа был сделан вывод о необходимости комплексного подхода, включающего противовирусную терапию, в лечении любых форм острых респираторных вирусных инфекций и гриппа. Background. Acute respiratory viral infections are a pathology that most often occurs in outpatient therapeutic practice (about 40 million cases per year). The term acute respiratory viral infection is a collective concept and denotes a group of diseases of viral etiology with predominant damage to the respiratory tract.The general epidemiological features of acute respiratory viral infections pathogens consist in common transmission: airborne droplets and through contact with contaminated objects. Although the causes of acute respiratory viral infections may be different, they have common epidemiological and clinical features that determine a unified strategy for treatment and prevention. Results. Treatment of acute respiratory viral infections is aimed at reducing the severity of symptoms, preventing progression of the disease, and achieving a complete and lasting recovery. Laboratory etiological diagnosis at the outpatient stage is carried out using molecular genetic methods only for influenza A and B, as well as COVID-19; to identify other pathogens of acute respiratory viral infections, it is advisable only for clinical and epidemiological indications, since the results obtained do not affect further tactics of patient management. A required component of treatment is non-drug therapy, including bed rest, diet and plenty of fluids.Drug treatment of acute respiratory viral infections and influenza includes etiotropic drugs, pathogenetic and symptomatic therapy. Direct and indirect antiviral drugs are used as etiotropic therapy. Neuraminidase inhibitors, like cap-dependent endonuclease inhibitors, are used in the treatment of influenza A and B, and, unfortunately, are not active against other pathogens of acute respiratory viral infections. Due to the lack of drugs with direct antiviral action active against acute respiratory viral infections pathogens, the main etiotropic drugs are drugs of indirect (immunomodulatory) action with a wide antiviral spectrum, which include interferon inducers. Conclusion. The article presents an analysis of the literature on the topic of optimizing the treatment of acute respiratory viral infections and influenza in an outpatient setting using drugs from the group of interferon inducers.As a result of the analysis, it was concluded that an integrated approach is necessary, including antiviral therapy in the treatment of any forms of acute respiratory viral infections and influenza.

Purpose. To study the features of the clinical course of coronavirus infection (COVID-19) in people living with HIV and risk factors for adverse outcomes. Materials and methods. The study included 523 patients with a confirmed diagnosis of COVID-19 occurring against the background of HIV infection and hospitalized from March 2020 to September 2021 on the basis of the GBUZ “S.P. Botkin KIB” in St. Petersburg. Two groups were formed: 1 – receiving antiretroviral therapy (n=204), 2 – not receiving ART (n=319). A comparative analysis of the results obtained during the examination was carried out using statistical methods: Mann-Whitney (p≤0.05) and the calculation of the relative risk (RR) when comparing the probability of the outcome of the disease depending on the presence of risk factors: respiratory rate ( NPV),% lung damage, levels of CD4 and C-reactive protein (CRP) with a significance level of p≤0.05. Results. Among the patients, persons aged 30 to 49 years predominated. In 50.5% of cases, coronavirus infection proceeded in the form of acute respiratory viral infections, pneumonia was diagnosed in 49.5%, which was subsequently complicated in 22.9% by the development of acute respiratory distress syndrome or sepsis in 2.1%. Severe course of COVID-19 was observed in non-adherent to ART, with CD4 lymphocyte count (≤50 cells/µl), multimorbidity and amounted to 45%. Conclusion. A feature of the course of COVID-19 in patients with HIV/SARS-COV-2 coinfection was a high number of deaths – 21.6%. In the overall structure of causes of death, the maximum share fell on HIV infection – 58.4%, COVID-19 – 24.8%, HIV/ COVID-19 –9.7% coinfection and other causes – 7.1%. Factors associated with the development of severe forms of coronavirus infection caused by SARS-COV-2 in HIV-infected patients who were hospitalized, the combination of which can be used as a predictor of death, have been identified: respiratory rate (RR) > 20 per minute, percentage of involvement lungs> 50%, CD4 lymphocyte level <40 cells/µl, CRP>50 mg/l, presence of three or more concomitant diseases.

The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined.

Positive results have been achieved during the implementation of the measles elimination program in the Russian Federation and in the Northwestern Federal District (NWFD). However, measles remains an urgent problem for some regions due to the peculiarities of this infection. Purpose of the work : to characterize the clinical, epidemiological and molecular genetic characteristics of measles in adults during the period of increasing incidence in St. Petersburg. Materials and methods : the incidence of measles in the Northwestern Federal District was analyzed in 2006–2020, and the data of 30 patients of S.P. Botkin clinical infectious diseases hospital over 18 years old (2018). The diagnosis of measles is confirmed by enzyme immunoassay. Molecular genetic studies (PCR, sequencing) were carried out at the National Scientific and Methodological Center for the Surveillance of Measles and Rubella of G.N. Gabrichevsky Moscow Scientific Research Institute of Epidemiology and Microbiology, biological material was used (nasopharyngeal washings, urine). Results : there was an increase in morbidity in some regions of the Northwestern Federal District in conditions of high coverage of the population with measles vaccinations. In the age structure in 2018–2019 the proportion of adults was 65%. 74% of patients were not vaccinated against measles. A moderate-severe course (100%) was noted, regardless of the genotypes of the virus. Clinical manifestations were characterized by febrile, catarrhal and exanthema syndrome. Diarrhea was found in 36,7% of patients, hepatomegaly in 43.4%, and an increase in transaminases in 87%. 66,7% of patients traveled outside St. Petersburg. The genotypes of the virus were identified: B3 Kabul and B3 Dublin of African origin, D8 Girsomnath of Indian origin. Conclusions : measles remains an urgent problem, in recent years, adults prevail among patients, both local and imported cases are recorded. The clinical course of the disease may be accompanied by intestinal complications and other symptoms that make it difficult to diagnose at the prehospital stage. The use of molecular genetic methods makes it possible to identify the pathogen, assess the identity of viral isolates, and improve the epidemiological surveillance of the infection.

The effect of the comorbid background on the course of the infectious process in chronic HCV infection requires study due to the existence of a risk of progression of liver fibrosis even after the eradication of the virus against the background of concomitant diseases.Material and methods. The article analyzes the prevalence of various comorbid conditions in 700 patients with chronic HCV infection, who were observed in the hospital of the Botkin in St. Petersburg, an assessment of the mutual influence of the comorbid background and the progression of liver fibrosis in HCV infection was given. To determine the contribution of comorbidity to the course of HCV infection, the odds ratio (OR) parameters were calculated.Results. HCV-infected individuals have higher prevalence of comorbidity (63 %) and multimorbidity (50 %). In patients with severe fibrosis or cirrhosis, the presence of the comorbidity factor increased to 85 %. In the examined group of patients, diseases of the biliary tract and pancreas prevailed (30.0 %), occult Hepatitis B Infection was revealed in 19.0 %, in 15.4 % – cardiovascular diseases, in 13.7 % – diseases of the upper gastrointestinal tract. Diabetes mellitus was found in 4.6 % of patients, and obesity – in 5.9 %, kidney disease – 3.0 %. The remaining concomitant diseases occurred in less than 2.0 % of the observed patients. It has been established that diseases of the biliary tract and pancreas, gastrointestinal tract, diabetes mellitus, obesity, cardiovascular diseases are risk factors for the development of liver fibrosis in chronic HCV infection.Conclusions. The data obtained indicate the need for a more personalized approach to monitoring patients and the need to create integrated models of medical care for patients with chronic hepatitis C.

Positive results have been achieved during the implementation of the measles elimination program in the Russian Federation and in the Northwestern Federal District (NWFD). However, measles remains an urgent problem for some regions due to the peculiarities of this infection.Purpose of the work: to characterize the clinical, epidemiological and molecular genetic characteristics of measles in adults during the period of increasing incidence in St. Petersburg.Materials and methods: the incidence of measles in the Northwestern Federal District was analyzed in 2006–2020, and the data of 30 patients of S.P. Botkin clinical infectious diseases hospital over 18 years old (2018). The diagnosis of measles is confirmed by enzyme immunoassay. Molecular genetic studies (PCR, sequencing) were carried out at the National Scientific and Methodological Center for the Surveillance of Measles and Rubella of G.N. Gabrichevsky Moscow Scientific Research Institute of Epidemiology and Microbiology, biological material was used (nasopharyngeal washings, urine).Results: there was an increase in morbidity in some regions of the Northwestern Federal District in conditions of high coverage of the population with measles vaccinations. In the age structure in 2018–2019 the proportion of adults was 65%. 74% of patients were not vaccinated against measles. A moderate-severe course (100%) was noted, regardless of the genotypes of the virus. Clinical manifestations were characterized by febrile, catarrhal and exanthema syndrome. Diarrhea was found in 36,7% of patients, hepatomegaly in 43.4%, and an increase in transaminases in 87%. 66,7% of patients traveled outside St. Petersburg. The genotypes of the virus were identified: B3 Kabul and B3 Dublin of African origin, D8 Girsomnath of Indian origin.Conclusions: measles remains an urgent problem, in recent years, adults prevail among patients, both local and imported cases are recorded. The clinical course of the disease may be accompanied by intestinal complications and other symptoms that make it difficult to diagnose at the prehospital stage. The use of molecular genetic methods makes it possible to identify the pathogen, assess the identity of viral isolates, and improve the epidemiological surveillance of the infection.

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod.Materials and methods: The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin.Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative.Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.

The work presents data on forty-one patients with chronic hepatitis C (HCV, genotype 1), at different liver fibrosis stages. The studies were performed in the course of interferon-containing treatment regimens, i.e., pegylated interferon combined with ribavirin and pegylated interferon; ribavirin together with NS3/4A inhibitor of HCV serine protease. Concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) were measured in blood plasma samples, using xMAP multiplex analysis. Flow cytometry studies were also performed in order to reveal cells with CCR6 and CXCR3 receptors in lymphocyte populations. The obtained results were analyzed using a statistical program package R. Results: 36 out of 41 patients achieved virological response, while 5 patients did not respond to the therapy. The responders were split into two groups, as follows: (1) liver fibrosis-free; (2) patients with fibrosis stages 1, 2 and 3. In the group of fibrosis-free patients, the decrease of CXCL11/ITAC concentration and the increase of TNFαwere observed, as well as increase of CTL CXCR3+ content by the 12th week of therapy and an increase of NK CXCR3+ by the end of treatment. In addition, this group exhibited a decrease in the CXCR3+ B lymphocyte contents at this timepoint. Concentrations of CCL2/MCP-1 during treatment were increased in the patients with different stages of liver fibrosis, as compared to baseline. By the end of therapy, an increase in the relative content of NK CXCR3+and TNK CCR6+ was also detected. The study confirmed a potential role of cytokines/chemokines TNFα, CCL2/MCP-1 and CXCL11/ITAC in activation of the cell-mediated immunity and elimination of the hepatitis C virus from the body. The results indicate that activation of T cellmediated immunity in both groups of the patients and reduction of B cells with CXCR3 receptor in the patients of first group is a positive prognostic factor showing efficiency of interferon therapy. Two of studied cytokines/ chemokines (TNFαand CCL20/MIP3α) differed in the groups of responders and non-responders at the start of therapy. Statistical evaluation of pre-treatment results has shown a tendency for differing concentration of TNFα, and CCL20/MIP3αamounts were significantly different for the patients of these groups. The plasma concentrations of CCL20/MIP3αin non-responders were > 4-fold higher than in responders to the therapy. Hence, the present study allowed us to propose the chemokine CCL20/MIP3α as a potential predictor of treatment outcomes in HCV infection.

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod. Materials and methods : The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin. Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative. Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.

Цитокины и хемокины играют ключевую роль в процессах воспаления и фиброгенеза при развитии хронического вирусного гепатита С. Комплексный анализ содержания цитокинов/хемокинов в крови больных хроническим вирусным гепатитом С может дать более полную информацию об иммунопатогенезе заболевания, его течении и прогнозе. Цель настоящего исследования - количественное определение цитокинов/хемокинов в крови больных хроническим вирусным гепатитом С на разных стадиях заболевания. Материалом исследования служила плазма крови. Пациентов с хроническим вирусным гепатитом С (n = 73), ранее не получавших противовирусную терапию, разделили на 3 группы в зависимости от степени фиброза печени, которые соответствуют стадиям заболевания. Контрольную группу составили практически здоровые лица (n = 37). Концентрацию цитокинов/хемокинов: IFNα, IFNγ, IFNλ/IL28а, TNFα, ССL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, ССL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC измеряли на приборе Luminex MAGFIX (Luminex, США) с использованием тест-систем «Milliplex MAP» (Millipore, США). Статистическую обработку данных осуществляли с применением программы GraphPad Prizm 6, Statistica 8. В плазме крови больных хроническим вирусным гепатитом С выявлен повышенный уровень TNFa и хемокинов: ССL2/MCP-1, CCL4/MIP-1β, ССL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10 и CXCL11/ITAC. По мере прогрессирования хронического вирусного гепатита С и фиброзирования печеночной ткани существенно возрастали концентрации цитокинов/хемокинов: TNFα, ССL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG. Наибольшая степень зависимости обнаружена между уровнями CXCL10/IP-10 и CXCL11/ITAC в плазме крови и выраженностью фиброза печени. Таким образом, данное исследование подтверждает значимость хемокинов в иммунопатогенезе хронического вирусного гепатита С, в том числе в процессах фиброгенеза.

We performed a comprehensive analysis of CCR6 and CXCR3 chemokine receptors and their ligands CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, and CXCL11/ITAC in the liver and blood of patients with chronic hepatitis C at different stages of the disease. TaqMan PCR was used to determine mRNA gene expression of chemokines and their receptors in liver specimens, xMAP multiplex analysis was performed to estimate the concentration of chemokines in blood plasma, and fl ow cytofluorometry was used to evaluate CCR6 and CXCR3 expression on peripheral blood lymphocyte populations. In the liver of patients with hepatitis C, mRNA expression of CXCL10, CCR6, and CXCR3 genes increases with fibrosis progression in the liver tissue. In the plasma, concentrations of all studied chemokines increased depending on the stage of liver fibrosis, CCR6 and CXCR3 expression was changed in various lymphocyte populations. Thus, chemokines are involved in the immunopathogenesis and fibrogenesis in chronic viral hepatitis C. The results suggest using these chemokines in the diagnosis and prognosis of the disease.