Increased formation of phosphorylated H2AX foci in nuclei of cells infected by hepatitis B AND B+D viruses
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01.01.2018 |
Kostyushev D.
Brezgin S.
Akostyusheva A.
Lipatnikov A.
Simirskil V.
Mamonova N.
Volchkova E.
Maleyev V.
Chulanov V.
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Voprosy Virusologii |
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Ссылка
© 2018 Ruslania. All rights reserved. Liver cirrhosis and hepatocellular carcinoma are the most common outcomes of chronic hepatitis B. Hepatitis B virus (HBV) induces transformation and cell death in chronic hepatitis B (CHB). DNA double strand breaks (DSBs) represent the most dangerous type of genome damage. It was shown previously that generation of phosphorylated histone H2AX foci is a reliable marker of DSBs. The aim of this study was to analyse generation of yH2AX foci in HBV and hepatitis D virus (HDV) infection in vitro and in liver biopsies of patients with CHB and CHB with delta-agent (CHD). Human hepatoma cell line HepG2-1.1merHBV with activated HBV life cycle was used to perform real-time PCR for analysis of pregenomic RNA, HBV DNA, HBV cccDNA and for immunocytochemical analysis of yH2AX. Liver biopsies from CHB and CHD patients were analyzed to confirm the results. HBV induces multiple discrete yH2AX foci in HepG2-1.1merHBV cells in vitro and in biopsies of CHB and CHB+D patients. The ratio of hepatocytes w/o yH2AX foci is significantly lower (49,9+7-12,3% vs. 85,5+/-0,9%, p<0,05), while the proportion of cells with 1-10 yH2AX foci is higher (49,3+7-12,6% vs. 14,5+/-0,9%, p<0,05) compared to healthy control. There is a significant increase In the mean number of yH2AX foci in biopsies from CHB+D patients (3,5+7-1,1 and 5,5+/-1,5 vs. 0,5+/-0,16 in control hepatocytes, p<0.05). The ratio of hepatocytes w/o yH2AX foci is significantly lower in CHB and CHB+D patients, while percentage of cells with 1-10 yH2AX foci is higher. Rare hepatocytes with multiple (11-30 yH2AX foci per cell) foci appear in CHB and CHB+D patients. In conclusion, yH2AX foci are generated in hepatocytes of CHB and CHB+D patients and can be utilized to assess genome damage, associated with HBV and HDV viral infection.
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Interim results of the international multicenter prospective observational study to evaluate the epidemiology, humanistic and economic outcomes of treatment for chronic hepatitis C virus (HCV) (MOSAIC)
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01.01.2018 |
Chulanov V.
Isakov V.
Zhdanov K.
Bakulin I.
Burnevich E.
Latarska-Smuga D.
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Infektsionnye Bolezni |
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© 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.
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Hepatitis B vaccination coverage of healthcare professionals in Greece
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01.01.2018 |
Psarrou A.
Moisoglou I.
Meimeti E.
Dounias G.
Kikemeni A.
Siakavellas S.
Leon G.
Katsarou M.
Lagiou M.
Izotov B.
Drakoulis N.
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Farmacia |
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© 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved. It has been reported that hepatitis B virus (HBV) is 10 times more infectious than hepatitis C virus (HCV) and 100 times more infectious than human immunodeficiency virus (HIV). Although there are two approved and very effective antivirals that quickly reduce the viral load (HBV DNA) and the risk of liver damage, vaccination prevention still represents the ideal intervention to reduce the spread of the disease and to protect public health. A literature review of the studies published in English on hepatitis B vaccination coverage of healthcare professionals in Greece during the 2006-2016 period was conducted. The literature review highlighted 12 studies. Healthcare professionals’ vaccine rate ranged between 55% and 88%. Doctors had the higher vaccination rate among healthcare professionals and registered nurses compared to nurses’ aides (p < 0.05). Higher educational level, knowledge of hepatitis B and a positive attitude toward vaccines (p < 0.05) revealed as the variables that affect positively healthcare professionals to be vaccinated. Mandatory vaccination of professionals within a health policy with regard to vaccination, as well as the implementation of information programs for them, are two important interventions that may increase vaccination coverage rates.
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Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017)
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01.01.2018 |
Vinnitskaya E.
Sandler Y.
Bakulin I.
Parfenov A.
Nikitin I.
Ilchenko L.
Bueverov A.
Lopatkina T.
Ignatova
Syutkin V.
Raikhelson K.
Khomeriki S.
Gudkova R.
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Terapevticheskii Arkhiv |
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Ссылка
© 2018 Media Sphera Publishing Group. All rights reserved. The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient.
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Clinical implications of hepatitis b virus rna and covalently closed circular dna in monitoring patients with chronic hepatitis b today with a gaze into the future: The field is unprepared for a sterilizing cure
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Чуланов Владимир Петрович
Волочкова Елена Васильевна
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GENES |
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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
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Публикация |
Clinical implications of hepatitis b virus rna and covalently closed circular dna in monitoring patients with chronic hepatitis b today with a gaze into the future: The field is unprepared for a sterilizing cure
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Чуланов Владимир Петрович (Профессор)
Волочкова Елена Васильевна (Заведующий кафедрой)
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GENES |
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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
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Публикация |