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Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin

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Journal of Animal Science and Biotechnology 2018年第1期9卷 119-126页

作者： Janina Skipor Marta Kowalewska Aleksandra Szczepkowska Anna Majewska Tomasz Misztal marek Jalynski Andrzej P.Herman Katarzyna Zabek Institute of Animal Reproduction and Food Research Polish Academy of Sciences The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences Veterinary Medicine Faculty University of Warmia and Mazury Department of Sheep and Goat Breeding Animal Bioengineering FacultyUniversity of Warmia and Mazury in Olsztyn

Background： Interleukin-1β（IL-1β） is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid（CSF） is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide（LPS）-induced ***： Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient（QAlb） was *** of IL-1β（Il1B） and its receptor type Ⅰ（Il1r1） and type Ⅱ（Il1r2） and matrix metalloproteinase（Mmp） 3 and 9 was evaluated in the choroid plexus（CP）.Results： Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, *** LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected m RNA expression of Il1B, Il1r1 and Il1r2 in the CP. The m RNA expression of Mmp3 and Mmp9 was not ***： The lack of correlation between plasma and CSF IL-1β concentration indicates that

关键词： Albumin Cerebrospinal fluid Ewes Interleukin-1β LPS Melatonin

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Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-β1,vascular endothelial growth factor,and basic fibroblast growth factor in patients with chronic hepatitis C

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World Journal of Gastroenterology 2006年第6期12卷 961-965页

作者： Ewa Janczewska-Kazek Bogdan marek Dariusz Kajdaniuk Halina BorgieI-marek Department of Infectious Diseases Medical University of Silesia Chorzow Poland Department of Pathophysiology Medical University of Silesia Zabrze Poland Medical University of Silesia KatowicePoland

AIM:To assess the role of transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)andbasic fibroblast growth factor(bFGF)in the pathogenesisof fibrosis associated with chronic hepatitis C(CHC)and to evaluate the influence of the antiviral therapyon above parameter levels depending on the treatmentresults(complete response or no response).METHODS:Study group included 100 patients withCHC,in whom fibrosis in liver specimens was assessed(Scheuer fibrosis score:1-4 points).Control groupincluded 30 subjects with antibodies anti-HCV presentand persistently normal ALT level,without fibrosis(Scheuer fibrosis score:0 points).Concentration ofstudied parameters was assayed in the serum byimmunoenzymatic method before and after the therapywith interferon alpha-2b and ***:TGF-β1 levels were significantly higher in thestudy group compared to the control group(35.89 vs 32.37ng/mL;P=0.023).Such differences were not found in VEGFand bFGF *** patients showing complete response(negative HCV RNA and normal ALT level),significantincrease in VEGF(112.8 vs 315.03 pg/mL;P<0.05)andbFGF(2.51 vs 15.79 pg/mL;P=0.04)levels were *** decrease in TGF-β1 level was observed bothin responders(37.44 vs 30.02 ng/mL;P=0.05),andin non-responders(38.22 vs 30.43 ng/mL;P=0.043).bFGF levels before the treatment were significantly lower(2.51 vs 5.94 pg/mL;P=0.04),and after the treatmentsignificantly higher(15.79 vs 4.35 pg/mL;P=0.01) in patients with complete response than in those with ***:Among the analyzed parametersTGF-β1 seems to play the most important role in thepathogenesis of fibrosis in *** of this factor aresignificantly lower in subjects who do not have fibrosisdeveloped in *** therapeutic effect in CHCpatients is associated with significant changes in TGF-β1,VEGF,and bFGF levels,bFGF seems to have the highestusefulness in the prognosis of treatment efficacy.

关键词：干扰素α 病毒唑血清治疗肝纤维化

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Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

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World Journal of Gastroenterology 2023年第25期29卷 4085-4098页

作者： Dorota Dybowska Dorota Zarebska-Michaluk Piotr Rzymski Hanna Berak Beata Lorenc marek Sitko Michal Dybowski Wlodzimierz Mazur Magdalena Tudrujek-Zdunek Justyna Janocha-Litwin Ewa Janczewska Jakub Klapaczynski Anna Parfieniuk-Kowerda Anna Piekarska Barbara Sobala-Szczygiel Krystyna Dobrowolska Malgorzata Pawlowska Robert Flisiak Department of Infectious Diseases and Hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Department of Infectious Diseases and Allergology Jan Kochanowski UniversityKielce 25-317Poland Department of Infectious Diseases Provincial HospitalKielce 25-317Poland Department of Environmental Medicine University of Medical SciencesPoznań60-806Poland Integrated Science Association Universal Scientific Education and Research NetworkPoznań60-806Poland Outpatient Clinic Hospital for Infectious Diseases in WarsawWarsaw 01-201Poland Pomeranian Center of Infectious Diseases Medical UniversityGdańsk 80-214Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 31-088Poland Utrecht University School of Economics Utrecht UniversityUtrecht 3584 ECNetherlands Clinical Department of Infectious Diseases Medical University of SilesiaChorzów 41-500Poland Department of Infectious Diseases Medical University of LublinLublin 20-059Poland Department of Infectious Diseases and Hepatology Medical University of WrocławWrocław 50-367Poland Department of Basic Medical Sciences Faculty of Public Health in BytomMedical University of SilesiaKatowice 40-007Poland Department of Internal Medicine and Hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarsaw 00-241Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-089Poland Department of Infectious Diseases and Hepatology Medical University ofŁódźŁódź91-347Poland Department of Infectious Diseases and Hepatology Medical University of SilesiaBytom 41-902Poland Collegium Medicum Jan Kochanowski UniversityKielce 25-317Poland

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect *** has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be *** To evaluate the effectiveness and safety of DAA in patients with various mental *** This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment *** entire study population was included in the intent-to-treat(ITT)***-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing *** Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychia

关键词： Hepatitis C Mental disorders Direct-acting antivirals

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On El Naschie’s Fractal-Cantorian Space-Time and Dark Energy—A Tutorial Review

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Natural Science 2015年第13期7卷 581-598页

作者： Leila marek-Crnjac Department of Mathematics Technical School Center of Maribor Maribor Slovenia

This tutorial review is dedicated to the work of the outstanding Egyptian theoretical physicist and engineering scientist Prof. Mohamed El Naschie. Every physics student knows the well-known Einstein’s mass-energy equation, E=mc2, but unfortunately for physics, few know El Naschie’s modification, E(O)=mc2/22, and El Naschie’s dark energy equation E(D)=mc2(21/22) although this new insight has truly far reaching implications. This paper gives a short tutorial review of El Naschie’s fractal-Cantorian space-time as well as dark energy. Emphasis is put on the fundamental concept of Cantor set, fractal dimensions, zero set, empty set, and Casimir effect.

关键词： E-Infinity Theory Dark Energy Casimir Effect Quantum Wave Quantum Particle Quantum Entanglement Nanotechnology Black Holes Information Paradox

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Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era

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World Journal of Gastroenterology 2023年第13期29卷 2015-2033页

作者： Michał Brzdęk Dorota Zarębska-Michaluk Piotr Rzymski Beata Lorenc Adam Kazek Magdalena Tudrujek-Zdunek Justyna Janocha-Litwin Włodzimierz Mazur Dorota Dybowska Hanna Berak Anna Parfieniuk-Kowerda Jakub Klapaczyński marek Sitko Barbara Sobala-Szczygieł Anna Piekarska Robert Flisiak Department of Infectious Diseases Jan Kochanowski UniversityKielce 25-317Poland Department of Infectious Diseases Jan Kochanowski UniversotyKielce 25-317Poland Department of Environmental Medicine Poznan University of Medical SciencesPoznań60-806Poland Integrated Science Association Universal Scientific Education and Research NetworkPoznań60-806Poland Pomeranian Center of Infectious Diseases Medical University GdańskGdańsk 80-214Poland ID Clinic Mysłowice 41-400Poland Department of Infectious Diseases Medical University of LublinLublin 20-059Poland Department of Infectious Diseases and Hepatology Medical University WrocławWrocław 50-367Poland Clinical Department of Infectious Diseases Clinical University of Silesia in KatowiceChorzów 41-500Poland Department of Infectious Diseases and Hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Daily Department Hospital for Infectious Diseases in WarsawWarszawa 01-201Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-089Poland Department of Internal Medicine and Hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarszawa 00-241Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 31-088Poland Department of Infectious Diseases Medical University of Silesia in KatowiceBytom 41-902Poland Department of Infectious Diseases and Hepatology Medical University ofŁódźŁódź90-419Poland

BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the *** of them is liver cirrhosis,which occurs in about 20%of patients chronically infected with the hepatitis C virus(HCV).Direct-acting antivirals(DAAs),which replaced interferon(IFN)-based regimens,significantly improved the prognosis of this group of patients,increasing HCV eradication rates and tolerability of *** study is the first to assess changes in patient profile,effectiveness,and safety in the HCV-infected cirrhotic population in the IFN-free *** To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the *** The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology *** retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter *** measure of treatment effectiveness was the percentage of sustained virologic response(SVR)calculated after excluding patients lost to *** data collected during therapy and the 12-wk post-treatment period included information on adverse events,including serious ones,deaths,and treatment *** The studied population(n=3577)was balanced in terms of gender in 2015-2017,while the following years showed the dominance of *** decline in the median age from 63 in 2015-2016 to 61 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and ***-experienced patients dominated in 2015-2016,while treatment-naive individuals gained an advantage in 2017 and reached 93.2%in ***(GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent *** effectiveness of the therapy was comparable regardless of the

关键词： Hepatitis C Liver cirrhosis Direct-acting antivirals Pangenotypic Genotype-specific Epidemiology

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PARTHIAN CITIES AND STRONGHOLDS IN TURKMENISTAN

欧亚学刊

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欧亚学刊 2015年第1期 117-125页

作者： marek Jan Olbrycht

The Arsacid Empire（247 BCE-CE 226）emerged as the result of a nomadic invasion of north-eastern Iran and southern *** tightly bound to their steppe heritage,the Arsacids showed a remarkable ability to adopt promptly and efficiently a number of the hallmarks associated with the sedentary peoples they subjugated,including the establishment of new cities and the building of strongholds.

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Understanding diarrhoeal diseases in response to climate variability and drought in Cape Town, South Africa: a mixed methods approach

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Infectious Diseases of Poverty 2023年第4期12卷 105-105页

作者： Tristan Taylor Lee Mohamed Aqiel Dalvie Martin Röösli Sonja Merten marek Kwiatkowski Hassan Mahomed Neville Sweijd Guéladio Cissé Swiss Tropical and Public Health Institute Allschwil Switzerland University of Basel Basel Switzerland Centre for Environmental and Occupational Health Research School of Public Health University of Cape Town Cape Town South Africa Metro Health Services Western Cape Government: Health and Wellness Western Cape South Africa Division of Health Systems and Public Health Department of Global Health Faculty of Medicine and Health Sciences Stellenbosch University Stellenbosch South Africa Alliance for Collaboration on Climate and Earth Systems Science Council for Scientific and Industrial Research Pretoria South Africa

BackgroundThe climate of southern Africa is expected to become hotter and drier with more frequent severe droughts and the incidence of diarrhoea to increase. From 2015 to 2018, Cape Town, South Africa, experienced a severe drought which resulted in extreme water conservation efforts. We aimed to gain a more holistic understanding of the relationship between diarrhoea in young children and climate variability in a system stressed by water *** a mixed-methods approach, we explored diarrhoeal disease incidence in children under 5 years between 2010 to 2019 in Cape Town, primarily in the public health system through routinely collected diarrhoeal incidence and weather station data. We developed a negative binomial regression model to understand the relationship between temperature, precipitation, and relative humidity on incidence of diarrhoea with dehydration. We conducted in-depth interviews with stakeholders in the fields of health, environment, and human development on perceptions around diarrhoea and health-related interventions both prior to and over the drought, and analysed them through the framework *** diarrhoeal incidence data, the diarrhoea with dehydration incidence decreased over the decade studied, e.g. reduction of 64.7% in 2019 [95% confidence interval (CI): 5.5–7.2%] compared to 2010, with no increase during the severe drought period. Over the hot dry diarrhoeal season (November to May), the monthly diarrhoea with dehydration incidence increased by 7.4% (95% CI: 4.5–10.3%) per 1 °C increase in temperature and 2.6% (95% CI: 1.7–3.5%) per 1% increase in relative humidity in the unlagged model. Stakeholder interviews found that extensive and sustained diarrhoeal interventions were perceived to be responsible for the overall reduction in diarrhoeal incidence and mortality over the prior decade. During the drought, as diarrhoeal interventions were maintained, the expected increase in incidence in the public health sector di

关键词： routine drought humidity

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The Microstructure and Oxidation Resistance of The Microstructure and Oxidation Resistance of Slurry Method on Rene 80 Superalloy

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Journal of Minerals and Materials Characterization and Engineering 2012年第7期11卷 719-723页

作者： marek Goral Research and Development Laboratory for Aerospace Materials Rzeszow University of Technology Powstancow Warszawy 12 35-959 Rzeszow Poland

The slurry method is one of the oldest techniques of deposition of aluminide coating on the nickel superalloy, titanium alloys and steel. It is characterized by relatively low costs of its realisation and necessary equipment. This method en-ables a simple modification of chemical composition of the coating through addition of different powders. The author showed study on the possibility of modification of the Al-Si slurry chemical composition used for aluminide coating deposition by addition of MeCrAlY powder. The slurry was deposited by immersion than the diffusion treatment at 950℃ for two hours was applied. The thickness of obtained coatings was in the range of 30 - 65 μm.

关键词： Slurry Method Aluminide Coatings Nickel Superalloy

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B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1251-1268页

作者： Cefan Zhou Xiaoting Zhu Nanxi Liu Xueying Dong Xuewen Zhang Huili Huang Yu Tang Shicheng Liu Mengyu Hu Ming Wang Xiaoling Deng Shi Li Rui Zhang Yuan Huang Hao Lyu Shuai Xiao Sang Luo Declan William Ali marek Michalak Xing-Zhen Chen Zhentian Wang Jingfeng Tang National“111”Center for Cellular Regulation and Molecular Pharmaceutics Key Laboratory of Fermentation Engineering(Ministry of Education)Hubei University of TechnologyWuhan 430068China Membrane Protein Disease Research Group Department of PhysiologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAB T6G2R3Canada Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province) Hubei Key Laboratory of Industrial MicrobiologyHubei University of TechnologyWuhanChina Department of Systems Biology for Medicine School of Basic Medical SciencesFudan Universityand Shanghai Fifth People’s HospitalFudan UniversityShanghai 200433China Department of Clinical Laboratory Renmin Hospital of Wuhan UniversityWuhan 430060China Ningxia Key Laboratory of Stem Cell and Regenerative Medicine General Hospital of Ningxia Medical UniversityNingxia 750001China Department of Biological Sciences University of AlbertaEdmontonAB T6G2R3Canada Department of Biochemistry University of AlbertaEdmontonAB T6G2R3Canada

Abnormal activation of Wnt/β-catenin-mediated transcription is closely associated with the malignancy of pancreatic *** with sequence similarity 83 member A(FAM83A)was shown recently to have oncogenic effects in a variety of cancer types,but the biological roles and molecular mechanisms of FAM83A in pancreatic cancer need further ***,we newly discovered that FAM83A binds directly toβ-catenin and inhibits the assembly of the cytoplasmic destruction complex thus inhibiting the subsequent phosphorylation and ***83A is mainly phosphorylated by the SRC non-receptor kinase family member BLK(B-lymphoid tyrosine kinase)at tyrosine 138 residue within the DUF1669 domain that mediates the FAM83A-β-catenin ***,FAM83A tyrosine 138 phosphorylation enhances oncogenic Wnt/β-catenin-mediated transcription through promotingβ-catenin-TCF4 interaction and showed an elevated nucleus translocation,which inhibits the recruitment of histone deacetylases by *** also showed that FAM83A is a direct downstream target of Wnt/β-catenin signaling and correlates with the levels of Wnt target genes in human clinical pancreatic cancer ***,the inhibitory peptides that target the FAM83A-β-catenin interaction significantly suppressed pancreatic cancer growth and metastasis in vitro and in *** results revealed that blocking the FAM83A cascade signaling defines a therapeutic target in human pancreatic cancer.

关键词： FAM83A elevated phosphorylation

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Best therapy for the easiest to treat hepatitis C virus genotype 1binfected patients

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World Journal of Gastroenterology 2022年第45期28卷 6380-6396页

作者： Dorota Zarębska-Michaluk Michal Brzdęk Jerzy Jaroszewicz Magdalena Tudrujek-Zdunek Beata Lorenc Jakub Klapaczyński Włodzimierz Mazur Adam Kazek marek Sitko Hanna Berak Justyna Janocha-Litwin Dorota Dybowska Łukasz Supronowicz Rafal Krygier Jolanta Citko Anna Piekarska Robert Flisiak Department of Infectious Diseases Jan Kochanowski UniversityKielce 25-317Poland Department of Infectious Diseases and Hepatology Medical University of SilesiaKatowice 40-055Poland Department of Infectious Diseases Medical University of LublinLublin 20-059Poland Pomeranian Center of Infectious Diseases Medical University GdańskGdańsk 80-214Poland Department of Internal Medicine and Hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarszawa 00-241Poland Clinical Department of Infectious Diseases Medical University of SilesiaChorzów 41-500Poland ID Clinic Mysłowice 41-400Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 31-088Poland Hospital for Infectious Diseases Hospital for Infectious DiseasesWarszawa 02-091Poland Department of Infectious Diseases and Hepatology Medical University WrocławWrocław 50-367Poland Department of Infectious Diseases and Hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-089Poland Infectious Diseases and Hepatology Outpatient Clinic Gemini NZOZŻychlin 62-571Poland Medical Practice of Infections Regional HospitalOlsztyn 10-561Poland Department of Infectious Diseases and Hepatology Medical UniversityŁódźŁódź90-419Poland

BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon *** To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological *** This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 *** effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up *** The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR *** effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/*** regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds

关键词： Hepatitis C Genotype 1b Direct-acting antivirals Pangenotypic Genotype-specific Sustained virologic response

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