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Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

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World Journal of Gastroenterology 2023年第6期29卷 949-966页

作者： MichałBrzdęk dorota zarębska-michaluk Federica Invernizzi Marta Cilla Krystyna Dobrowolska Robert Flisiak Collegium Medicum Jan Kochanowski UniversityKielce 25-516Poland of Infectious Diseases Jan Kochanowski UniversityKielce 25-516Poland Center for Liver Disease Division of Internal Medicine and HepatologyIRCCS Ospedale San RaffaeleMilan 20-132Italy Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-540Poland

Chronic infection with the hepatitis C virus(HCV)remains a major health problem affecting approximately 58 million people *** the era of interferon(IFN)-based regimens,patients particularly infected with genotypes 1 and 4 achieved a low response *** implementation of direct-acting antivirals changed the landscape of HCV *** increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by *** the following years,there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the *** optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over *** treated with antiviral therapies were younger in successive periods,less burdened with comorbidities and comedications,more frequently treatment-naïve and had less advanced liver *** the IFN-free era,specific subpopulations such as patients with HCV/HIV coinfection,those with a history of previous treatment,patients with renal impairment or with cirrhosis had lower chances for a virologic ***,these populations should no longer be considered difficult to *** the high effectiveness of HCV therapy,there is a small percentage of patients with treatment ***,they can be effectively retreated with pangenotypic rescue regimens.

关键词： Hepatitis C virus Interferon Direct-acting antiviral Epidemiology Chronic hepatitis C

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

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

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

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World Journal of Gastroenterology 2021年第18期27卷 2177-2192页

作者： Ewa Janczewska Mateusz Franciszek Kołek Beata Lorenc Jakub Klapaczyński Magdalena Tudrujek-Zdunek Marek Sitko Włodzimierz Mazur dorota zarębska-michaluk Iwona Buczyńska dorota Dybowska Agnieszka Czauż-Andrzejuk Hanna Berak RafałKrygier Jerzy Jaroszewicz Jolanta Citko Anna Piekarska Beata Dobracka Łukasz Socha Zbigniew Deroń Łukasz Laurans Jolanta Białkowska-Warzecha Olga Tronina Brygida Adamek Krzysztof Tomasiewicz Krzysztof Simon Malgorzata Pawłowska Waldemar Halota Robert Flisiak Department of Basic Medical Sciences The School of Health Sciences in BytomMedical University of SilesiaBytom 41-902Poland Department of Animal Physiology Faculty of BiologyUniversity of WarsawWarszawa 02-096Poland 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 02-507Poland Department of Infectious Diseases Medical University of LublinLublin 20-081Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 30-688Poland Clinical Department of Infectious Diseases Medical University of Silesia in KatowiceChorzów 41-500Poland Department of Infectious Diseases Jan Kochanowski University KielceKielce 25-369Poland Department of Infectious Diseases and Hepatology Medical University WrocławWrocław 51-149Poland Department of Infectious Diseases and Hepatology Ludwik Rydygier Collegium Medicum in Bydgoszcz Faculty of Medicine Nicolaus Copernicus University in ToruńBydgoszcz 85-030Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-540Poland One-Day Department Hospital for Infectious Diseases in WarsawWarszawa 01-201Poland Outpatient Clinic State University of Applied Sciences in KoninKonin 62-510Poland Department of Infectious Diseases and Hepatology Medical University of Silesia in KatowiceBytom 41-902Poland Department of Medical Practice of Infections Regional HospitalOlsztyn 10-561Poland Department of Infectious Diseases and Hepatology Medical University ofŁódźŁódź90-419Poland MedicalSpec Center Wrocław 53-428Poland Department of Infectious Diseases Hepatology and Liver TransplantationPomeranian Medical UniversitySzczecin 71-455Poland Ward of Infectious Diseases and Hepatology Biegański Regional Specialist HospitalŁódź91-347Poland Infectious and Liver Diseases Clinic Multidisciplinary Regional HospitalGorzów Wielkopolski 66-400Poland Dep

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for ***,few researchers have analyzed the factors causing therapy failure in some *** To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world *** The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from *** collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)*** events observed during the treatment and follow-up period were *** standard and machine learning methods were used for statistical *** During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype *** cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 *** included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass *** viral factors,genotype 3 and viral load also exerted an influence on treatment *** statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed

关键词： Advanced liver disease Chronic hepatitis C Direct-acting antiviral drugs Sustained virologic response Interferon-free therapy Antiviral therapy

Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered

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Journal of Molecular Cell Biology 2024年第2期16卷 1-10页

作者： dorota Kmiec Frank Kirchhoff Institute of Molecular Virology Ulm University Medical Center89081 UlmGermany

Extensive studies on HIV-1 have led to the discovery of a variety of structurally and functionally diverse innate defense factors that target various steps of the retroviral replication *** of them,such as APOBEC3,tetherin,and SERINC5,are well *** importance is evident from the fact that HIV-1 uses its accessory proteins Vif,Vpu,and Nef to counteract ***,the list of antiviral factors is constantly increasing,and accumulating evidence suggests that innate defense mechanisms,which restrict HIV-1 and/or are counteracted by viral proteins,remain to be *** antiviral factors are relevant to diseases other than HIV/AIDS,since they are commonly active against various viral *** this review,we provide an overview of recently reported antiretroviral factors and viral countermeasures,present the evidence suggesting that more innate defense mechanisms remain to be discovered,and discuss why this is a challenging but rewarding task.

关键词： HIV-1 restriction factors viral antagonists interferon-stimulated genes antiviral factors

Changes in the adult sex ratio of six duck species breeding populations over two decades

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Avian Research 2024年第2期15卷 202-210页

作者： Monika Homolkova Petr Musil Diego Pavon-Jordan dorota Gajdosova Zuzana Musilova Sarka Neuzilova Jan Zouhar Department of Ecology Faculty of Environmental SciencesCzech University of Life Sciences PragueKamýcka 129CZ-16521Prague–SuchdolCzech Republic Department of Terrestrial Ecology Norwegian Institute for Nature Research(NINA)PO Box 5685 TorgardenTrondheimN-7485Norway Department of Econometrics Faculty of Informatics and StatisticsUniversity of Economicsnam.W.Churchilla 4CZ-13067Prague 3Czech Republic

Despite all efforts,long-term changes in the adult sex ratios of breeding duck populations are still unclear;this uncertainty is especially true for male-bias populations,which are often under the scrutiny of researchers lacking convenient results for the active protection of endangered *** with male-bias populations are usually strongly affected by a decline in population size that leads to a higher extinction *** this study,we examined our long-term data of the abundance of breeding populations in six duck species(Mallard Anas platyrhynchos,Gadwall Mareca strepera,Red-crested Pochard Netta rufina,Common Pochard Aythya ferina,Tufted Duck Aythya fuligula,and Common Goldeneye Bucephala clangula)from fishponds in South Bohemia,Czechia,between 2004 and *** evidence was used to assess long-term changes in the adult sex ratio in these breeding populations and investigate the possible effects of the NAO index(North Atlantic Oscillation index)on them,indicating climate conditions in *** determined a long-term decrease of the proportion of females in the breeding season in two of the six examined species:Common Pochard and Red-crested Pochard,which is driven by the long-term increase in the number of males in contrast to the decreasing or stable number of females likely caused by different migration behaviours between females and *** the case of Common Pochard,in breeding populations,we estimated 60-65%of males in the early 2000s rising to 75-80%in the early ***,we establish no significant effects linked to climate conditions of the previous winter in these species as a crucial cause of the changes of the proportion of females in the breeding population.

关键词： Adult sex ratio Breeding population Population dynamics Red-listed species Waterfowl Winter weather conditions

A single degenerated primer significantly improves COX1 barcoding performance in soil nematode community profiling

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Soil Ecology Letters 2024年第2期6卷 31-44页

作者： Yincai Ren dorota L. Porazinska Quanhui Ma Shuhan Liu Hongmei Li Xue Qing Department of Plant Pathology Nanjing Agricultural UniversityNanjing210095China Department of Entomology and Nematology University of FloridaGainesvilleFL32611USA Institute of Grassland Science Key Laboratory of Vegetation Ecology of the Ministry of EducationJilin Songnen Grassland Ecosystem National Observation and Research StationNortheast Normal UniversityChangchun130024China

A new COX1 primer for soil nematode metabarcoding was designed,and this primer outperforms other commonly used COX1 primer pairs in species recovery and quantity of PCR products.•The lack of reference database is the main reason that led to the low species recovery in COX1 metabarcoding.•We expanded current NCBI database by adding 51 newly generated COX1 reference *** nematodes play important roles in soil ecosystems and often serve as bioindicators of soil *** identification of soil nematodes is often difficult due to their limited diagnostic characters and high phenotypic *** barcoding and metabarcoding techniques are promising but lack universal primers,especially for mitochondrial COX1 *** this study a degenerated COX1 forward primer COIFGED was *** primer pair(COIFGED/JB5GED)outperforms other four commonly used COX1 primer pairs in species recovery and quantity of polymerase chain reaction(PCR)*** metabarcoding analysis,the reads obtained from the new primer pair had the highest sequencing saturation threshold and amplicon sequence variant(ASV)diversity in comparison to other COX1 as well as 18S rRNA *** annotation of ASVs suggested the new primer pair initially recovered 9 and 6 out of 25 genera from mock communities,respectively,outperformed other COX1 primers,but underperformed the widely used 18S NF1/18Sr2b primers(16 out of 25 genera).By supplementing the COX1 database with our reference sequences,we recovered an additional 6 mock community species bringing the tally closer to that obtained with 18S *** summary,our newly designed COX1 primers significantly improved species recovery and thus can be supplementary or alternative to the conventional 18S metabarcoding.

关键词： degenerated primers DNA metabarcoding mitochondrial cytochrome oxidase c subunit I gene phylogeny ribosomal RNA gene soil nematodes

Fuel poverty and low carbon emissions: a comparative study of the feasibility of the hybrid renewable energy systems incorporating combined heat and power technology

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Frontiers in Energy 2022年第2期16卷 336-356页

作者： dorota RZETELSKA Madeleine COMBRINCK Department of Mechanical and Construction Engineering Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle-upon-TyneNE18STUK

Fuel poverty is most prevalent in North East England with 14.4%of fuel poor households in Newcastle upon *** aim of this paper was to identify a grid connected renewable energy system coupled with natural gas reciprocating combined heat and power unit,that is cost-effective and technically feasible with a potential to generate a profit from selling energy excess to the grid to help alleviate fuel *** system was also aimed at low carbon *** models were designed and optimized with the aid of the HOMER Pro *** were compared with respect to their economic,technical,and environmental performance.A solution was proposed where restrictions were placed on the size of renewable energy *** configuration consists of 150 kW CHP,300 kW PV cells,and 30 kW wind *** renewable fraction is 5.10%and the system yields a carbon saving of 7.9%in comparison with conventional *** initial capital investment is$1.24 million which enables the system to have grid sales of 582689 kWh/a.A conservative calculation determined that 40%of the sales can be used to reduce the energy cost of fuel poor households by$706 per *** solution has the potential to eliminate fuel poverty at the site analyzed.

关键词： greenhouse gas control low carbon target grid connected renewable fraction fuel poverty combined heat and power HOMER Pro

Application of monodispersive anion exchangers in sorption and separation of Y^3＋ from Nd^3＋ and Sm^3＋ complexes with dcta

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Journal of Rare Earths 2008年第5期26卷 619-625页

作者： Halina Hubicka dorota Kolodynska Department of Inorganic Chemistry Faculty of Chemistry Maria Curie-Sklodowska University Maria Curie-Sklodowska Sq.3 20-031 Lublin Poland

Rare earth complexes with trans-1,2-diaminocyclohexane-N,N,N ,N -tetraacetic acid （DCTA） of the Ln（dcta） type exhibited an unusual sequence of affinity on the polystyrene anion exchangers： pm^3＋〉Nd^3＋〉Sm^3＋〉Pr^3＋〉Ce^3＋〉Eu^3＋〉Gd^3＋〉La^3＋〉Sc^3＋〉Tb^3＋〉Dy^3＋〉 Ho^3＋〉Y^3＋〉Er^3＋〉Tm^3＋〉Yb3＋〉Lu^3＋[1]. Taking into account the position of Y^3＋, Sm^3＋, and Nd^3＋ in this affinity series, for the monodispersive polystyrene anion exchangers, Lewatit MonoPlus M 500, Lewatit MonoPlus M 600, Lewatit MonoPlus MP 500, Lewatit MonoPlus MP 64, and for the heterodispersive anion exchanger, Lewatit MP 62, the weight （Dg） and bed （Dv） distribution coefficients of these complexes and working ion exchange capacities （Cw） were determined. Based on these values, purifications of Y^3＋ from Nd^3＋ and Y^3＋ from Sm^3＋ in the macro-micro component system on these anion exchangers were studied. The application potential of this method was highlighted for the separation of Y^3＋ in the presence of Nd^3＋ and Sm^3＋. With 1 L of monodispersive and strongly basic polystyrene gel anion exchanger Lewatit MonoPlus M 500 in the acetate form, it is possible to obtain approximately 79 g Y2O3 purified from Nd2O3 and 70 g Y2O3 purified from Sm2O3 in the same process condition.

关键词： DCTA rare earth complexes anion exchange