Репозиторий Университета

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The composite Y14/siUTR, a complex consisting of cationic lipopeptide Y14 as an excipient and pharmaceutical substance of small interfering RNAtargeted against the UTR region of hepatitis C virus (siUTR), was investigated. The composite was intended to inhibit the hepatitis C virus replication cycle. The present work was aimed at developing pharmaceutical analytical methods for the components of this composite using HPLC-UV and UV spectroscopy.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferon-based schemes found to be non-effective or contraindicated. 3D therapy was the only available etiotropic option for them. New safety data published after the start of our study significantly limited usage of this regimen among patients with non-compensated cirrhosis. The aim of this study was to evaluate efficacy and safety of the 3D interferon-free regimen among HCV Gt1b patients with non-compensated cirrhosis. Method: 66 patients (26 males and 40 females) with HCV Gt1b and non-compensated cirrhosis were enrolled. All of them were treated with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks. Ribavirin was discontinued after 4 weeks of therapy due to onset of new data on the efficacy of 3D regimen without ribavirin in Turquoise III study published in September 2015 before the change of package insert. Child-Pugh score was assessed before the start of antiviral therapy as follows: 21 patients (31,8%) – 9 points, 11 patients (16,7%) – 8 points, 34 patients (51,5%) – 7 points. The key method used to evaluate study results was modified intent-to-treat (mITT) analysis because number of analyzed patients within treatment period changed after withdrawal caused by safety reasons but followed by assessment of efficacy among patients who discontinued treatment. Per protocol (PP) method was also used in addition to mITT. Results: Aviremia after 14 days of treatment was reached among 35 out of 65 patients (53,8%), rapid virologic response – among 79,7% patients (51/64). Each patient who received full 12-week course of treatment (n=60) including those who discontinued due to safety reasons (n=3) between 14th and 30th days of therapy reached SVR12 and SVR24. Assessment of Child-Pugh score in 6 months after EOT demonstrated decrease by 3-4 points among 21 patients (33,9%) and by 1-2 points among 35 patients. 66,1% patients reached clinical improvement in MELD score. Treatment discontinuation was caused by progression of hepatic encephalopathy and/or jaundice (4 cases). Those adverse events regressed among majority of patients after discontinuation of therapy. 3 deaths were reported (bacterial endocarditis, progression of hepatic encephalopathy and bleeding from gastric ulcers) during treatment period and 1 death in follow-up period due to progression of hepatocellular carcinoma. Conclusion: 3D therapy was effective in 100% patients (mITT) with HCV GT1b and non-compensated cirrhosis both among those who completed full therapy course and those who discontinued the therapy due to safety reasons. Safety analysis demonstrated that the rate of severe adverse events was comparable with natural course of HCV-infection in patients on non-compensated cirrhotic stage without antiviral treatment.

© 2018 Russian Transplant Society. All rights reserved. Chronic HCV infection is the leading cause of liver transplantation in adults in developed countries. Unfortunately, the reinfection of the graft inevitably occurs in all patients with persistent replication of the virus. Against the background of the necessary immunosuppressive therapy, the progression of the disease accelerates, leading to rapid decompensation of the liver. Antiviral therapy significantly improves the results of transplantation, but the use of standard interferon-based regimens is associated with low efficacy (no more than 30% for the most common 1 genotype of the virus) and poor tolerance. The article describes new interferon-free oral regimens used to treat the recurrence of HCV infection of 1 genotype.

© 2018 Russian Transplant Society. All Rights Reserved. HCV infection is one of the most common causes leading to the development of terminal liver diseases – cirrhosis and hepatocellular carcinoma, the main treatment for which is orthotopic liver transplantation. However, with continued virus replication, 100% reinfection occurs, which leads to the rapid progression of cirrhosis of the graft and the loss of its function. Standard interferon-containing therapy is ineffective for HCV infection, especially genotype 1, both before and after transplantation, and also has a wide range of adverse events. The article presents the successful experience of treating the recurrence of HCV infection 1 genotype in a patient who underwent liver transplantation and several courses of ineffective antiviral therapy.

© 2018 Russian Transplant Society. All Rights Reserved. Aim. To study the efficacy and safety of the use of paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin in liver recipients with recurrence of HCV 1 genotype after transplantation. Materials and methods. The study included 46 patients after orthotopic liver transplantation with recurrence of HCV 1 genotype. 37 patients completed a 24-week course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin. The effectiveness of the therapy was calculated as the proportion of patients who achieved aviremia 12 weeks after the end of the course of treatment. The safety of therapy was assessed by the number of adverse events that occurred during the course of antiviral therapy. Results. A sustained virologic response at 12 weeks after the end of the course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir, reached 100% of the recipients of the liver. Reduction in the intensity of cytolytic and cholestatic syndromes was noted at week 4 of therapy. Adverse events were recorded in 56.7% of the subjects, mostly they were not severe and were stopped on their own. Acute cellular rejection of the transplant developed in 1 patient (2.7%). There have been no cases of irreversible liver transplant dysfunction or death of the recipient. The conclusion. The use of paritaprevir, ritonavir, ombitasvir and dasabuvir is safe and effective in the treatment of relapse of HCV infection of 1 genotype after liver transplantation.

© 2018 Media Sphera Publishing Group.All Rights Reserved. In the article we present three clinical observations demonstrating that HCV infection in patients with remission of Wilson disease causes an recrudescence of the disease, in one of the observations - decompensation of liver cirrhosis. In this study we first describe on the successful treatment of HCV infection with direct antiviral drugs in patients with Wilson disease. Establishment of all factors of liver damage and successful treatment (elimination of the virus, adequate lifelong medical treatment) allow to expect a favorable prognosis in patients with a combination of Wilson disease and HCV infection.

© 2018 Media Sphera Publishing Group. All rights reserved. Hepatitis C virus (HCV) is a global population problem due to its high prevalence, usually late diagnosis, the difficulties of treatment. In the prognosis of patients with HCV not only hepatic, but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (CG), are important. Mixed CG is currently considered as a B-cell benign lymphoproliferative disorders. The role of HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin's lymphoma (NHL). The purpose of the review was to provide an overview of recent literature data and the meta-analysis of epidemiological data explaining the role of HCV in the development of NHL. The review also discusses the treatment for HCV-associated NHL by antiviral therapy or other therapeutic options, such as chemotherapy.

© 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.