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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.

Background. Even 100 years after the first attempts to introduce the chemotherapeutic approaches (in 1918) and despite the completely formed notions of myeloproliferative diseases as a group of malignant neoplasms, in the majority of patients with Ph-negative myeloproliferative neoplasms (MPN), a symptomatic, in fact, therapy approach – the impact on peripheral blood indices and nonspecific thromboprophylaxis – is allowed. The limitations of classical cytoreduction and current targeted therapy, as well as the conviction of most specialists in the impossibility of adequately containment of disease progression, continue to be the main factors that keep physicians from the early start of pathogenetic therapy. Objective: to study the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b) in early (non-risk-adjusted) therapy of classical Ph-negative myeloproliferative neoplasms in initial use and after therapy with other pegylated interferons (PEG-IFN). Materials and methods. Twenty seven patients with polycythemia vera or essential thrombocythemia, without considering risk, received cePEG-IFN alpha-2b: initially, or after 6 or 12 months of other pegylated interferon therapy, in a dosage of 200 μg per week, with a decrease to 100 μg per week if 2 degree hematological toxicity developed. Hematological and molecular responses were assessed. Follow-up – from 20 to 46 months. Results. In all groups, a hematologic response comparable in depth and dynamics, as well as a molecular response as a steady decrease in the JAK2V617F allelic load, was achieved. There was no effect on the results of change to therapy with cePEG-IFN alpha-2b. CePEGIFN alpha-2b showed less dose-limiting toxicity for neutropenia and better pharmacoeconomic feasibility. Discussion . New data about mechanisms of antiproliferative effects of interferon alfa preparations are given. The pharmacological advantages of cePEG-IFN alpha-2b are discussed: superiority in pharmacokinetic parameters, the presence of one position isomer purity of the drug substance, the convenience of self-application. Conclusion . Early administration of an effective pathogenic therapy is an independent preventive measure to prevent the MPN progression and complications development. The use of cePEG-IFN alpha-2b may help to improve the care of MPN patients.

To study the immune manifestations of the interferon-lambda 3 genepolymorphism in chronic viral hepatitis C, 110 Russian children (54 girls and 56 boys) with chronic HCV infection aged from 3 to 17 years were examined. All children were on combined therapy (pegylated interferon + ribavirin). It was found that among the studied polymorphic variants of the IFN-λ 3 gene in children with chronic HCV infection, T allele of the marker rs12979860 is associated with infection and chronization of HCV. The T/T rs12979860 genotype of the IFN-λ3 gene is unfavorable for the course of chronic HCV infection due to low levels of activated T-lymphocytes, intactness of the proinflammatory cytokines TNF-α, IL-6, IL-1α, and interferon-γ inducible protein IP-10. The revealed relation of the polymorphic variants of C/C + C/T locus rs12979860 of INF-λ3 gene with the expression of activated T-lymphocytes discloses the protective nature of these genotypes to the development of chronic HCV infection in children.

Хронические миелопролиферативные заболевания (ХМПЗ) представляют собой группу клональных гемопоэтических расстройств стволовых клеток, характеризующихся аберрантной пролиферацией одной или нескольких миелоидных линий. У больных моложе 20 лет ХМПЗ встречаются крайне редко, например, истинная полицитемия (ИП) примерно 2 случая на 10 млн в год. Истинная распространенность ИП и стандарты терапии больных детского возраста не определены. Цель. Анализ выявленных случаев ИП у больных моложе 20 лет и создание алгоритма выбора терапии. Материалы и методы. Проведен анализ 7 больных с ИП в возрасте до 18 лет (от 3 месяцев до 14 лет), из них 6 мальчиков и 1 девочка. Больным выполнялись общеклинические исследования, морфологическое, гистологическое, цитогенетическое, молекулярногенетическое исследования костного мозга, ультразвуковые исследования органов брюшной полости и сосудов. Циторедуктивная терапия проводилась пегилированным интерфероном, а при отсутствии ответа руксолитинибом. Результаты. В дебюте заболевания у всех больных выявлена спленомегалия различной степени, общее количество лейкоцитов 10,0 109/л, количество нейтрофилов 6,213,5 109/л, количество эритроцитов 5,68,9 1012/л, у 4 больных количество тромбоцитов было 1000 109/л (11033000 109/л). Случаев тромбоза или кровоточивости ни у кого отмечено не было. В 100 случаев выявлена мутация гена JAK2 (6 больных с мутацией JAK2V617F, 1 больной с мутацией в экзоне 12 гена JAK2 с.16131616delACAAinsT). Аллельная нагрузка в дебюте заболевания составляла 1433 (n 4) и 3566 (n 3). При терапии пегилированным интерфероном 2a (pegINF 2a) полный ответ на терапию был достигнут в 2 случаях, частичный ответ еще в 2 случаях, в одном из них терапия была прекращена в связи с выраженной токсичностью. Терапия второй линии (руксолитиниб) проводилась 3 больным у которых через 6 месяцев была достигнута частичная ремиссия (снижение гематокрита до менее 45 без кровопусканий). Переносимость руксолитиниба была удовлетворительной, какихлибо нежелательных явлений, требовавших снижения дозы или полной отмены, отмечено не было. Заключение. Учитывая крайнюю редкость ИП у больных моложе 18 лет, а также отсутствие результатов длительного наблюдения (исходы заболевания: частота прогрессии в острый миелоидный лейкоз или миелофиброз), необходимо продолжить сбор информации о больных с дебютом заболевания ранее 18 лет. У больных моложе 18 лет в качестве первой линии циторедуктивной терапии целесообразно использовать pegINF 2a, при отсутствии ответа и/или в случае непереносимости препарата переходить на вторую линию терапии руксолитиниб, при отсутствии ответа или прогрессии фиброза в костном мозге (MF2 и более) единственным методом, приводящим к излечению, является трансплантация аллогенных гемопоэтических стволовых клеток., Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic disorders of stem cells characterized by aberrant proliferation of one or more myeloid lines. MPNs are extremely rare in patients younger than 20 years old, for example, polycythemia vera (PV) is about 2 cases per 10 million people per year. The true prevalence of PV and treatment standards for pediatric patients are not defined. The goal is to analyze the identified cases of polycythemia vera (PV) in patients younger than 20 years and create an algorithm for the choice of therapy. Materials and methods. The analysis of 7 patients with PV at the age under 18 years (3 months 14 years), 6 of them are boys and 1 is girl. The patients underwent general clinical studies, morphological, histological, cytogenetic, molecular genetic studies of the bone marrow, ultrasound studies of the abdominal organs and vessels. Cytoreductive therapy was performed with pegylated interferon, and in the absence of a response ruxolitinib. Results. In the debut of the disease, splenomegaly of various degrees was detected in all patients, the total number of leukocytes (WBC) 10.0 109/L, the number of neutrophils 6.213.5 109/L, the number of red blood cells (RBC) 5.68.9 1012/L, in 4 patients platelet count (PLT) 1000 109/L (11033000 109/L). No cases of throm bosis or bleeding were noted. In 100 of cases, a mutation was detected in the JAK2 gene (6 patients with the mutation JAK2V617F, 1 patient with a mutation in exon 12 of the JAK2 gene p.16131616delACAAinsT). The allelic load in the debut of the disease was 1433 (n 4) and 3566 (n 3). With pegylated interferon 2 (pegINF 2a) therapy, a full response to therapy was obtained in 2 cases, a partial response in 2 cases, in one of them the therapy was discontinued due to pronounced toxicity. Secondline therapy (ruxolitinib) was performed in 3 patients and after 6 months partial remission was achieved in the form of a hematocrit decrease of less than 45 without bloodletting. The tolerability of ruxolitinib is satisfactory no adverse events requiring dose reduction or complete withdrawal were noted. Conclusion. Considering the extremely rare occurrence of PV in patients younger than 18 years of age, as well as the results of longterm followup (disease outcomes: frequency of progression in acute myeloid leukemia or myelofibrosis), it is necessary to continue collecting information on patients with debut of the disease earlier than 18 years. For patients younger than 18 years old, it is advisable to use pegINF 2a as the first line of cytoreductive therapy, in the absence of response and/or in case of intolerance to pegINF 2a, switch to the second line of therapy, ruxolitinib, in the absence of response or progression of bone marrow fibrosis (MF2 and more) it is necessary to consider the transplantation of allogeneic hematopoietic stem cells as the only curative method., №4 (2019)

Objectives. To provide clinical and laboratory characteristics of chronic hepatitis C in Vietnam. Materials and methods. A retrospective analysis of data about 1870 HCV patients observed at Hepatology Clinic in Ho Chi Minh City, Vietnam from 2010 to 2015. Results. Among observed patients, HCV genotype 1 is predominant (48.8%), genotype 6 was registered in 29,7% of patients, and genotype 2 – 18,7%. Advanced fibrosis (F3) and cirrhosis (F4) were detected in 52% of patients. The rate of chronic co-infection with hepatitis B viruse and hepatitis C virus is at 6% of patients. Nearly one-tenth of all observed HCV patients (9%) were diagnosed with hepatocellular carcinoma. In the group of patients who completed the full course of treatment, non-responsers to therapy and have virologic breakthrough, SVR-24 was registered at 73,7% and 75,1% of patients treated with simple or pegylated interferon, respectively. Thus, combination therapy with interferonalpha and ribavirin for the indigenous Vietnamese population has been showed relatively high efficiency. Conclusion. The findings about clinical and laboratory characteristics of patients with chronic hepatitis C, and the effectiveness of antiviral therapy, have practical importance for preparation a long-term strategy for the elimination of hepatitis C in Vietnam.

Аnalogues of nucleos(t)ides (AN) such as lamivudine (LAM), telbivudine (TBV), adefovir (ADP), entecavir (ENT) are widely used for the treatment of chronic hepatitis B (CHB). However, the prolonged treatment using these drugs often leads to the development of drug resistance. The most common substitutions in the reverse transcriptase are methionine for valine (rtM204V), or methionine for isoleucine (rtM204I) at position 204. Early AN-resistant mutations detection is of great importance to determine the treatment strategy of patients with CHB. Currently there are many highly sensitive methods for detection of drug resistance mutations, such as next-generation sequencing, reverse hybridizationbased line probe assay (LiPA), mass spectrometry. However, these methods require expensive equipment and reagents, and they are not widely used in clinical laboratories. The aim of this study was to develop a simple and accurate real-time PCR method for detection of rtM204I/V mutation. This method showed high specificity and sensitivity (1000 copies/ml), it is less laborious and does not require additional equipment, fast and cost effective compared to other methods. HBV mutations of resistance to AN were determined in 5 groups of patients with CHB. Patients of the first group received monotherapy with pegylated interferon (n = 12), the second group — lamivudine (n = 10), the third group — telbivudine (n = 7), the fourth group — entecavir (n = 15). The fifth group consisted of patients who did not receive antiviral therapy (n = 3). The frequency of mutations in HBV polymerase YMDD-motif was determined among 47 patients with CHB: it was 10% for lamivudine treated patients, 20% — for entecavir, 28% — for telbivudine. YIDD/YVDD motifs were identified in two patients and YMDD/YIDD — in one patient. Real-time PCR method for the detection of AN-resistant rtM204I/V mutations in HBV polymerase can be used in routine diagnostics for primary screening of patients not responding to AN treatment. The application of this method can reduce the number of samples for in-depth study of primary and compensatory mutations of resistance to AN by sequencing method. The developed method versus Sanger-sequencing is fast, economical, and provides the detection of minor variants of HBV populations.