Репозиторий Университета

© 2018, MDPI AG. All rights reserved. Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study the effectiveness, safety and tolerance of Viferon® (human recombinant interferon alpha-2b with antioxidants vitamins Е and С) as compared with standard therapy in complex treatment of mixed female urogenital infections during pregnancy and the effect of Viferon® on the formation of immunity in ontogenesis and during the early adaptation period of newborns. Patients and methods. The study included 70 women aged 18 to 40 years with mixed urogenital infections. The treatment group included 36 patients, who received etiotropic antimicrobial and antiviral therapy, underwent correction of immune status disorders and restoration of vaginal colonisation resistance. Along with standard therapy, patients of the treatment group received Viferon®, suppositories 500 000 IU, according to the schedule: 1 suppository 2 times/day every day for 10 days, then 1 suppository 2 times/day for 9 days with a 3-day interval. Aftre that, Viferon®, suppositories 150 000 IU 1 suppository 2 times daily every day for 5 days every 4 weeks until delivery. The control group comprised 34 patients who received standard therapy without interferon correction. All patients received standard therapy appropriate for their disease. Results. Among the patients receiving Viferon®, the development of placental insufficiency was recorded by 2 times more rarely. In the treatment group (Viferon®), fetal growth restriction (IUGR) was diagnosed only in 8.3%. In the control group, IUGR was found in 22% (OR + 2.65). In the treatment group, the incidence of fetal CMV infection was reduced by 16 timesd anf of herpesvirus infection type 2 – by 10 times. In the group of patients who did not use Viferon®, the share of newborns with CNS lesions amounted to 18.4%, whereas in the treatment group it approached 6.5% (OR –2.83). Inclusion of Viferon® in complex therapy resulted in a lower incidence of infectious lesions of the skin and mucous membranes of the newborn infants (amniotic fluid infection syndrome) by 5.8 times. Colclusion. The use of Viferon® (human recombinant interferon alpha-2b with antioxidants vitamins Е and С) suppositories in complex therapy in pregnant women with infection promotes a faster elimination of viruses, a significant decrease of the signs of threatened miscarriage, premature labour, risk for developing PI and IUGR, associated with inflammatory process (p < 0.05).

© 2018 Dynasty Publishing House. All rights reserved. The lecture deals with treatment of patients with CIN associated with papillomavirus infection (HPVI). The issues of epidemiology, diagnosis and treatment of CIN are discussed. Emphasis is put on a complex approach to treating patients with HPVI-associated CIN. Special attention is paid to studying the mechanisms of dysregulation of immune response during the period of human papillomavirus virus (HPV) persistence, which promotes immune suppression and is considered to be a necessary precondition for progression of HPV-associated cancer. Based on analysis of literature sources, the authors show that high oncogenic risk E6 and E7 HPV types interact with key proteins of interferon signalling pathway, inhibiting its production. This accounts for insufficient effectiveness of preparations of pure interferons and their inductors for treatment of HPV infection. From the pathogenetic positions, the use of inosine pranobex as a medication in complex therapy would be appropriate, since it ensures complete elimination of HPV and reduces the frequency of HPV infection recurrences.

© 2018 Media Sphera Publishing Group.All Rights Reserved. The aim of the study was to evaluate the clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of IFN-α2b with antioxidants in the treatment of acute respiratory infections (ARIs) in comparison with other variants of antiviral therapy. Materials and methods. A total of 90 servicemen aged 19.2±0.9 years with uncomplicated forms of ARI were hospitalized not later than 48 hours after the onset of the disease. Patients were randomized into 3 groups of 30 people each. In the first group, patients received rectal suppositories containing IFN-α2b (1 million IU) and antioxidants (alpha-tocopherol acetate and ascorbic acid) twice a day for 5 days. In the second group, patients received intranasally a gel formulation containing IFN-α2b (36 000 IU/1 g) and antioxidants 3 times a day in addition to the above suppositories. In the third group, patients were prescribed umifenovir (reference drug) at dose of 200 mg 4 times a day for 5 days. The dynamics of regression of clinical manifestations of ARI in different groups, changes in concentrations of IFN-α and IFN-γ in blood plasma, as well as spontaneous and induced production of these cytokines by blood cells ex vivo were evaluated. After that, the patients were observed for another 3 months to register repeated cases of hospitalization for ARI. Results. Marked tendency to accelerate the regression of symptoms of intoxication and fever was observed when intranasal dosage form of IFN-α2b was administered to patients receiving the rectal form of this cytokine. The combination of rectal and topical dosage forms of IFN-α2b with antioxidants was more effective than monotherapy with the rectal suppositories in preventing repeated hospitalization for ARI. The above combination caused the most complete correction of induced production of IFN-α by blood cells ex vivo at its initial deviation from the norm. Conclusion. The obtained data indicate the expediency of using the combination of rectal and topical dosage forms of IFN-α2b with antioxidants for treatment of ARI.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study clinico-epidemiological characteristics of patients with CHC and to evaluate clinical, economic and other parameters related to their treatment. Patients and methods. The study is conducted in 10 countries in Central and Eastern Europe involving 1.500-2000 patients with chronic HCV infection, aged 18 years and older not current receiving treatment for hepatitis and seeking for care in a routine clinical visit to physician. After enrollment, patients are observed until the end of HCV treatment. The study includes three consecutive phases. At the phase 1 epidemiological data for the patients seeking for care is being collected at the single visit. Patients for whom antiviral IFN-containing treatment is planned to be started within 12 weeks from the first visit were included into the second phase. During phase 2 patients are being assessed on-treatment for HRQoL changes over time, the impact of HCV and treatment on work productivity, activities of daily living and resource utilization. Interim results presented in this paper reflect epidemiologic characteristics of HCV patients collected during the first phase of MOSAIC study on the territory of Russia. Results. Data from 492 patients were collected in 15 study centers in Russia. 441 patients (377 treatment naïve, 64 experienced) entered the study, 51 patients were considered non-participants. 161 patients did not start treatment within 12 weeks after enrollment. Patients were of white race, 57% males and 43% females, aged between 19 and 74 years, with median age 37.0 (IQR 31-47 years). Median time since HCV diagnosis was 2.0 years. 30 (6.8%) patients had clinically compensated liver cirrhosis, 40% of patients had unknown cirrhosis status. The most common viral genotypes were Gt1 and Gt3 – 55.6% and 37.6% of patients, respectively. Among patients with known viral load HCV RNA level at enrollment was ≤ 800.000 IU/ml in 53% of patients and > 800.000 IU/ml in 47% of patients. Twelve (4.3%) treated patients had extra-hepatic symptoms of liver disease, no association was found between liver cirrhosis and presence of extra-hepatic manifestations (p = 0.3534). 14.5% of patients were treatment experienced, 88.9% of them had only one course of antiviral therapy in the past. Relapse was the most common reason of therapy failure observed in 50% (32/64) patients.17.5% of HCV patients have concomitant diseases; the most common are cardiovascular diseases (5,7%), other liver diseases (5%) and diabetes mellitus (2,9%), the latter is associated with the presence of liver cirrhosis (p = 0.0125). Among studied parameters (gender, age, HCV genotype and pre-treatment status) age was an only significant predictor of liver cirrhosis development, odds increase with every 10 years of increment (OR 2.005 [95% CI 1.407; 2.858], ROC 0.732, p = 0.0001). Conclusion. Epidemiology of patients with HCV infection was investigated in the first phase of MOSAIC international observational study on the territory of Russia and described in the present article. Сlinical, humanistic and economic burden of anti-HCV treatment based on MOSAIC data will be presented in future publications.

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text