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

Author

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, and Robert Flisiak

Subjects
Gastroenterology, General Medicine
Published
2023
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2. Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies

Author

Jerzy Jaroszewicz, Dorota Zarębska-Michaluk, Justyna Janocha-Litwin, Anna Parfieniuk-Kowerda, Marek Sitko, Anna Piekarska, Jolanta Białkowska, Dorota Dybowska, Aleksandra Murawska-Ochab, and Robert Flisiak

Subjects
Internal Medicine
Abstract

Despite the overall excellent efficacy of pangenotypic direct-acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to therapy.This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in pangenotypic failures.The study included patients treated with the pangenotypic regimen selected from the EpiTer-2 database, real-world project evaluating DAA-based treatment in Poland.Among 15,123 patients, 4,345 received one course of pangenotypic treatment (PAN-group) and 48 patients were retreated with pangenotypic regimens after pangenotypic failure (PAP-group). Patients from PAP-group were more often males (79% vs 53%, P0.001), had higher BMI (27.5 IQR:25.7-30.1 vs 25.7 IQR: 22.9-28.7 kg/m2, P0.001), were more often infected with genotype (GT) 3 (58% vs 27%, P0.001) and more frequently had liver cirrhosis (46% vs 21%, P0.001) compared with the PAN-group. Importantly, no significant difference in treatment effectiveness was found between PAP and PAN-groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P=0.39) in intent-to-treat and 91.5% vs 97.6% (P=0.17) in per protocol analysis. The selection of a specific retherapy regimen did not affect SVR.Our study demonstrated the excellent effectiveness of pangenotypic regimens and that most DAA non-responders could be successfully retreated with next pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors such as GT3 infection, cirrhosis, and male sex.

Published
2023
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3. Implementation of the web-based calculator estimating odds ratio of severe COVID-19 for unvaccinated individuals in a country with high coronavirus-related death toll

Author

Miroslaw Kwasniewski, Urszula Korotko, Karolina Chwialkowska, Magdalena Niemira, Jerzy Jaroszewicz, Barbara Sobala‐Szczygiel, Beata Puzanowska, Anna Moniuszko‐Malinowska, Sławomir Pancewicz, Anna Parfieniuk‐Kowerda, Diana Martonik, Dorota Zarebska‐Michaluk, Krzysztof Simon, Monika Pazgan‐Simon, Iwona Mozer‐Lisewska, Maciej Bura, Agnieszka Adamek, Krzysztof Tomasiewicz, Małgorzata Pawłowska, Anna Piekarska, Aleksandra Berkan‐Kawinska, Andrzej Horban, Justyna Kowalska, Regina Podlasin, Piotr Wasilewski, Arsalin Azzadin, Miroslaw Czuczwar, Michal Borys, Pawel Piwowarczyk, Slawomir Czaban, Jacek Bogocz, Magdalena Ochab, Anna Kruk, Sandra Uszok, Agnieszka Bielska, Anna Szałkowska, Justyna Raczkowska, Gabriela Sokołowska, Joanna Chorostowska‐Wynimko, Aleksandra Jezela‐Stanek, Adriana Rozy, Urszula Lechowicz, Urszula Połowianiuk, Agnieszka Tycinska, Kamil Grubczak, Aleksandra Starosz, Wiktoria Izdebska, Tadeusz F. Krzemiński, Jean Bousqet, Genoveffa Franchini, Jennifer Hadlock, Adam Kretowski, Mubeccel Akdis, Cezmi A. Akdis, Milena Sokolowska, Andrzej Eljaszewicz, Robert Flisiak, and Marcin Moniuszko

Subjects
Immunology, Immunology and Allergy
Published
2022
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4. High CD163 Expression on Classical Monocytes Is Associated with Immune Control of HBV Infection in Noncirrhotic Patients

Author

Robert Flisiak, Anatol Panasiuk, Anna Parfieniuk-Kowerda, Magdalena Świderska, Marcin Moniuszko, Magdalena Maciaszek, Kamil Grubczak, Andrzej Eljaszewicz, and Jerzy Jaroszewicz

Subjects
0301 basic medicine, HBsAg, Article Subject, CD14, Immunology, CD16, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Antigen, Pathology, medicine, RB1-214, Seroconversion, medicine.diagnostic_test, business.industry, Monocyte, virus diseases, Cell Biology, digestive system diseases, 030104 developmental biology, medicine.anatomical_structure, 030211 gastroenterology & hepatology, business, CD163
Abstract

Background and Aims. The functional impairment of monocytes may contribute to the persistence of HBV infection. This study aims to assess monocyte subpopulations, monocyte expression of CD163, plasma sCD163, and sTWEAK in patients with chronic HBeAg-negative HBV infection at different phases of disease. Methods. Fifty-nine patients with CHB, 9 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 15 healthy volunteers. Subpopulations of peripheral blood monocytes were distinguished by CD14 and CD16. Membrane expression of CD163 was assessed by flow cytometry, plasma sCD163 concentration by ELISA, and sTWEAK by bead-based multiplexed immunoassay system. Results. CD163 expression was increased in classical and intermediate monocytes in CHB patients and those with HBsAg/anti-HBs seroconversion. CD163 expression on classical monocytes was associated with status of immune control and thus significant in HBV infection as compared to active hepatitis. Plasma sCD163 concentration was increased in CHB patients and those with HBsAg/anti-HBs seroconversion vs. the control group. Positive correlations between plasma sCD163 and ALT, as well as APRI, were observed. Plasma sTWEAK concentration was lower in CHB patients in comparison to patients with HBsAg/anti-HBs seroconversion. Conclusions. Exposure to HBV antigens alters monocyte subsets’ frequencies and activation. The expression of CD163 on classical monocytes increased in parallel with improved immune control of the HBV infection. Patients who seroconverted HBsAg had the highest expression of CD163 on monocytes, which suggests involvement of monocytes in immune control of HBV infection. Persistent inflammation is accompanied by higher CD163 expression and sCD163 level and lower sTWEAK level.

Published
2020
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5. Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens

Author

Olga Tronina, Michał Brzdęk, Dorota Zarębska-Michaluk, Dorota Dybowska, Beata Lorenc, Ewa Janczewska, Włodzimierz Mazur, Anna Parfieniuk-Kowerda, Anna Piekarska, Rafał Krygier, Jakub Klapaczyński, Hanna Berak, Jerzy Jaroszewicz, Aleksander Garlicki, Krzysztof Tomasiewicz, Jolanta Citko, and Robert Flisiak

Subjects
pangenotypic, Infectious Diseases, Virology, sustained virologic response, chronic hepatitis C, direct-acting antivirals, interferon-free, rescue therapy
Abstract

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.

Published
2023
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6. Implementation of the User-Friendly Odds Ratio Calculator for Unvaccinated Individuals in a Country with a High COVID-19 Death Toll

Author

Miroslaw Kwasniewski, Urszula Korotko, Karolina Chwialkowska, Magdalena Niemira, Jerzy Jaroszewicz, Barbara Sobala-Szczygiel, Beata Puzanowska, Anna Moniuszko-Malinowska, Sławomir Pancewicz, Anna Parfieniuk-Kowerda, Diana Martonik, Dorota Zarębska-Michaluk, Krzysztof Simon, Monika Pazgan-Simon, Iwona Mozer-Lisewska, Maciej Bura, Agnieszka Adamek, Krzysztof Tomasiewicz, Małgorzata Pawłowska, Anna Piekarska, Aleksandra Berkan-Kawińska, Andrzej Horban, Justyna Kowalska, Regina Podlasin, Piotr Wasilewski, Arsalin Azzadin, Miroslaw Czuczwar, Michal Borys, Pawel Piwowarczyk, Slawomir Czaban, Jacek Bogocz, Magdalena Ochab, Anna Kruk, Sandra Uszok, Agnieszka Bielska, Anna Szalkowska, Justyna Raczkowska, Gabriela Sokolowska, Joanna Chorostowska-Wynimko, Aleksandra Jezela-Stanek, Adroana Rozy, Urszula Lechowicz, Urszula Polowianiuk, Agnieszka Tycinska, Kamil Grubczak, Aleksandra Starosz, Wiktoria Izdebska, Tadeusz Faustyn Krzeminski, Jean Bousquet, Milena Sokolowska, Genoveffa Franchini, Jennifer Hadlock, Adam Kretowski, Andrzej Eljaszewicz, Robert Flisiak, and Marcin Moniuszko

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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7. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

Author

Fallerini, Chiara, Picchiotti, Nicola, Baldassarri, Margherita, Zguro, Kristina, Daga, Sergio, Fava, Francesca, Benetti, Elisa, Amitrano, Sara, Bruttini, Mirella, Palmieri, Maria, Croci, Susanna, Lista, Mirjam, Beligni, Giada, Valentino, Floriana, Meloni, Ilaria, Tanfoni, Marco, Minnai, Francesca, Colombo, Francesca, Cabri, Enrico, Fratelli, Maddalena, Gabbi, Chiara, Mantovani, Stefania, Frullanti, Elisa, Gori, Marco, Crawley, Francis P, Butler-Laporte, Guillaume, Richards, Brent, Zeberg, Hugo, Lipcsey, Miklos, Hultström, Michael, Ludwig, Kerstin U, Schulte, Eva C, Pairo-Castineira, Erola, Baillie, John Kenneth, Schmidt, Axel, Frithiof, Robert, Mari, Francesca, Renieri, Alessandra, Furini, Simone Simone Furini, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Maurizio, Spagnesi, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Gabriella, Doddato, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Valentina, Perticaroli, Francesca, Ariani, Miriam Lucia Carriero, Laura Di Sarno, Diana, Alaverdian, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Leonardo Gianluca Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Sandro, Mancarella, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Francesco, Raimondi, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Menè, Roberto, Umberto, Zuccon, Lucia, Vietri, Stefano, Ceri, Pietro, Pinoli, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Raffaele, Bruno, Marco, Vecchia, Marta, Colaneri, Serena, Ludovisi, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Tomas, Luther, Anders, Larsson, Katja Hanslin Anna Gradin, Sarah, Galien, Sara Bulow Anderberg, Jacob, Rosén, Sten, Rubertsson, Hugo, Zeberg, Robert, Frithiof, Miklós, Lipcsey, Michael, Hultström, Sara Clohisey Peter Horby, Johnny, Millar, Julian, Knight, Hugh, Montgomery, David, Maslove, Lowell, Ling, Alistair, Nichol, Charlotte, Summers, Tim, Walsh, Charles, Hinds, Malcolm, G Semple, Peter J, M Openshaw, Manu, Shankar-Hari, Antonia, Ho, Danny, Mcauley, Chris, Ponting, Kathy, Rowan, J Kenneth Baillie, Fiona, Griffiths, Wilna, Oosthuyzen, Jen, Meikle, Paul, Finernan, James, Furniss, Ellie, Mcmaster, Andy, Law, Sara, Clohisey, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Lee, Murphy, Angie, Fawkes, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Max Head Fourman, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Marie, Zechner, Nicholas, Parkinson, Erola, Pairo-Castineira, Lucija, Klaric, Andrew, D Bretherick, Konrad, Rawlik, Dorota, Pasko, Susan, Walker, Nick, Parkinson, Clark, D Russell, Anne, Richmond, Elvina, Gountouna, David, Harrison, Wang, Bo, Yang, Wu, Alison, Meynert, Athanasios, Kousathanas, Loukas, Moutsianas, Zhijian, Yang, Ranran, Zhai, Chenqing, Zheng, Graeme, Grimes, Jonathan, Millar, Barbara, Shih, Jian, Yang, Xia, Shen, Chris, P Ponting, Albert, Tenesa, Andrew, Law, Veronique, Vitart, James, F Wilson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthorpe, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, Marotti, M, Arbane, G, Bonner, S, Hugill, K, Reid, J, Welters, I, Waugh, V, Williams, K, Shaw, D, J Fernandez Roman, M Lopez Martinez, Johnson, E, Waite, A, Johnson, B, Hamilton, O, Mulla, S, Mcphail, M, Smith, J, K Baillie, J, Barclay, L, Hope, D, Mcculloch, C, Mcquillan, L, Clark, S, Singleton, J, Priestley, K, Rea, N, Callaghan, M, Campbell, R, Andrew, G, Marshall, L, Mckechnie, S, Hutton, P, Bashyal, A, Davidson, N, Summers, C, Polgarova, P, Stroud, K, Pathan, N, Elston, K, Agrawal, S, Battle, C, Newey, L, Rees, T, Harford, R, Brinkworth, E, Williams, M, Murphy, C, White, I, Croft, M, Bandla, N, Gellamucho, M, Tomlinson, J, Turner, H, Davies, M, Quinn, A, Hussain, I, Thompson, C, Parker, H, Bradley, R, Griffiths, R, Scriven, J, Gill, J, Puxty, A, Cathcart, S, Salutous, D, Turner, L, Duffy, K, Puxty, K, Joseph, A, Herdman-Grant, R, Simms, R, Swain, A, Naranjo, A, Crowe, R, Sollesta, K, Loveridge, A, Baptista, D, Morino, E, Davey, M, Golden, D, Jones, J, J Moreno Cuesta, Haldeos, A, Bakthavatsalam, D, Vincent, R, Elhassan, M, Xavier, K, Ganesan, A, Purohit, D, Abdelrazik, M, Morgan, J, Akeroyd, L, Bano, S, Warren, D, Bromley, M, Sellick, K, Gurr, L, Wilkinson, B, Nagarajan, V, Szedlak, P, Cupitt, J, Stoddard, E, Benham, L, Preston, S, Slawson, N, Bradshaw, Z, Brown, J, Caswell, M, Smelling, Bamford, P, Faulkner, M, Cawley, K, Jeffrey, H, London, E, Sainsbury, H, Nagra, I, Nasir, F, Dunmore, Ce, Jones, R, Abraheem, A, Al-Moasseb, M, Girach, R, Brantwood, C, Alexander, P, Bradley-Potts, J, Allen, S, Felton, T, Manna, S, Farnell-Ward, S, Leaver, S, Queiroz, J, Maccacari, E, Dawson, D, C Castro Delgado, R Pepermans Saluzzio, Ezeobu, O, Ding, L, Sicat, C, Kanu, R, Durrant, G, Texeira, J, Harrison, A, Samakomva, T, Willis, H, Hopkins, B, Thrasyvoulou, L, Jackson, M, Zaki, A, Tibke, C, Bennett, S, Woodyatt, W, Kent, A, Goodwin, E, Brandwood, C, Clark, R, Smith, L, Rooney, K, Thomson, N, Rodden, N, Hughes, E, Mcglynn, D, Clark, C, Clark, P, Abel, L, Sundaram, R, Gemmell, L, Brett, M, Hornsby, J, Macgoey, P, Price, R, Digby, B, O'Neil, P, Mcconnell, P, Henderson, P, Henderson, S, Sim, M, Kennedy-Hay, S, Mcparland, C, Rooney, L, Baxter, N, Pogson, D, Rose, S, Daly, Z, Brimfield, L, K Phull, M, Hussain, M, Pogreban, T, Rosaroso, L, E Salciute, L Grauslyte, Brealey, D, Wraith, E, Maccallum, N, Bercades, G, Hass, I, Smyth, D, Reyes, A, Martir, G, D Clement, I, Webster, K, Hays, C, Gulati, A, Hodgson, L, Margarson, M, Gomez, R, Baird, Y, Thirlwall, Y, Folkes, L, Butler, A, Meadows, E, Moore, S, Raynard, D, Fox, H, Riddles, L, King, K, Kimber, S, Hobden, G, Mccarthy, A, Cannons, V, Balagosa, I, Chadbourn, I, Gardner, A, Horner, D, Mclaughlanv, D, Charles, B, Proudfoot, N, Marsden, T, L Mc Morrow, Blackledge, B, Pendlebury, J, Harvey, A, Apetri, E, Basikolo, C, Catlow, L, Doonan, R, Knowles, K, Lee, S, Lomas, D, Lyons, C, Perez, J, Poulaka, M, Slaughter, M, Slevin, K, Thomas, V, Walker, D, Harris, J, Drummond, A, Tully, R, Dearden, J, Philbin, J, Munt, S, Rishton, C, O'Connor, G, Mulcahy, M, Dobson, E, Cuttler, J, Edward, M, Rose, A, Sloan, B, Buckley, S, Brooke, H, Smithson, E, Charlesworth, R, Sandu, R, Thirumaran, M, Wagstaff, V, J Cebrian Suarez, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Solesbury, A, Kittridge, L, Forsey, M, Maloney, G, Cole, J, Davies, R, Hill, H, Thomas, E, Williams, A, Duffin, D, Player, B, Radhakrishnan, J, Gibson, S, Lyle, A, Mcneela, F, Patel, B, Gummadi, M, Sloane, G, Dormand, N, Salmi, S, Farzad, Z, Cristiano, D, Liyanage, K, Thwaites, V, Varghese, M, Meredith, M, Mills, G, Willson, J, Harrington, K, Lenagh, B, Cawthron, K, Masuko, S, Raithatha, A, Bauchmuller, K, Ahmad, N, Barker, J, Jackson, Y, Kibutu, F, Bird, S, Watson, G, Martin, J, Bevan, E, C Wrey Brown, Trodd, D, English, K, Bell, G, Wilcox, L, Katary, A, Gopal, S, Lake, V, Harris, N, Metherell, S, Radford, E, Moore, F, Bancroft, H, Daglish, J, Sangombe, M, Carmody, M, Rhodes, J, Bellamy, M, Garg, A, Kuravi, A, Virgilio, E, Ranga, P, Butler, J, Botfield, L, Dexter, C, Fletcher, J, Shanmugasundaram, P, Hambrook, G, Burn, I, Manso, K, Thornton, D, Tebbutt, J, Penn, R, Hulme, J, Hussain, S, Maqsood, Z, Joseph, S, Colley, J, Hayes, A, Ahmed, C, Haque, R, Clamp, S, Kumar, R, Purewal, M, Baines, B, Frise, M, Jacques, N, Coles, H, Caterson, J, S Gurung Rai, Brunton, M, Tilney, E, Keating, L, Walden, A, Antcliffe, D, Gordon, A, Templeton, M, Rojo, R, Banach, D, S Sousa Arias, Fernandez, Z, Coghlan, P, Williams, D, Jardine, C, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Garland, Z, Gumbrill, B, Phillips, C, L Ortiz-Ruiz de Gordoa, Peasgood, E, Tridente, A, K Shuker, S Greer, Lynch, C, Pothecary, C, Roche, L, Deacon, B, Turner, K, Singh, J, G Sera Howe, Paul, P, Gill, M, Wynter, I, Ratnam, V, Shelton, S, Naisbitt, J, Melville, J, Baruah, R, Morrison, S, Mcgregor, A, Parris, V, Mpelembue, M, Srikaran, S, Dennis, C, Sukha, A, Verlande, M, Holding, K, Riches, K, Downes, C, Swan, C, Rostron, A, Roy, A, Woods, L, Cornell, S, Wakinshaw, F, Creagh-Brown, B, Blackman, H, Salberg, A, Smith, E, Donlon, S, Mtuwa, S, Michalak-Glinska, N, Stone, S, Beazley, C, Pristopan, V, Nikitas, N, Lankester, L, Wells, C, S Raj, A, Fletcher, K, Khade, R, Tsinaslanidis, G, Mcmahon, M, Fowler, S, Coventry, T, Stewart, R, Wren, L, Mwaura, E, Mew, L, Scaletta, D, Williams, F, Inweregbu, K, Lancaster, N, Cunningham, M, Daniels, A, Harrison, L, Hope, S, Jones, S, Crew, A, Wray, G, Matthews, J, Crawley, R, Carter, J, Birkinshaw, I, Ingham, J, Scott, Z, Howard, K, Joy, R, Roche, S, Clark, M, Purvis, S, Morrison, A, Strachan, D, Clements, S, Black, K, Parmar, C, Altabaibeh, A, Simpson, K, Mostoles, L, Gilbert, K, L, Ma, Alvaro, A, Thomas, M, Faulkner, B, Worner, R, Hayes, K, Gendall, E, Blakemore, H, Borislavova, B, Goff, E, Vuylsteke, A, Mwaura, L, Zamikula, J, Garner, L, Mitchell, A, Mepham, S, Cagova, L, Fofano, A, Holcombe, H, Praman, K, Szakmany, T, E Heron, A, Cherian, S, Cutler, S, Roynon-Reed, A, Randell, G, Convery, K, K Stammers, D Fottrell-Gould, Hudig, L, Keshet-Price, J, Peters, M, O'Neill, L, Ray, S, Belfield, H, Mchugh, T, Jones, G, Akinkugbe, O, Tomas, A, Abaleke, E, Beech, E, Meghari, H, Yussuf, S, Bamford, A, Hairsine, B, Dooks, E, Farquhar, F, Packham, S, Bates, H, Armstrong, L, Kaye, C, Allan, A, Medhora, J, Liew, J, Botello, A, Anderson, F, Cusack, R, Golding, H, Prager, K, Williams, T, Leggett, S, Golder, K, Male, M, Jones, O, Criste, K, Marani, M, Anumakonda, V, Amin, V, Karthik, K, Kausar, R, Anastasescu, E, Reid, K, Jacqui, M, Hormis, A, Walker, R, Duncan, T, Uriel, A, Ustianowski, A, T-Michael, H, Bruce, M, Connolly, K, Smith, K, Partridge, R, Griffin, D, Mcdonald, M, Muchenje, N, Martin, D, Filipe, H, Eastgate, C, Jackson, C, Gratrix, A, Foster, L, Martinson, V, Stones, E, Caroline, Abernathy, Parkinson, P, Reed, A, Prendergast, C, Rogers, P, Woodruff, M, Shokkar, R, Kaul, S, Barron, A, Collins, C, Beavis, S, Whileman, A, Dale, K, Hawes, J, Pritchard, K, Gascoyne, R, Stevenson, L, Jha, R, Lim, L, Krishnamurthy, V, Parker, R, Turner-Bone, I, Wilding, L, Reddy, A, Whiteley, S, Wilby, E, Howcroft, C, Aspinwall, A, Charlton, S, Ogg, B, Menzies, D, Pugh, R, Allan, E, Lean, R, Davies, F, Easton, J, Qiu, X, Kumar, S, Darlington, K, Houston, G, O'Brien, P, Geary, T, Allan, J, Meikle, A, Hughes, G, Balasubramaniam, M, Latham, S, Mckenna, E, Flanagan, R, Sathe, S, Davies, E, Chablani, M, Kirkby, A, Netherton, K, Archer, S, Yates, B, Ashbrook-Raby, C, Cole, S, Casey, M, Cabrelli, L, Chapman, S, Austin, P, Hutcheon, A, Whyte, C, Almaden-Boyle, C, Pattison, N, Cruz, C, Vochin, A, Kent, H, Thomas, A, Murdoch, S, David, B, Penacerrada, M, Lubimbi, G, Bastion, V, Wulandari, R, Valentine, J, Clarke, D, Serrano-Ruiz, A, Hierons, S, Ramos, L, Demetriou, C, Mitchard, S, White, K, White, N, Pitts, S, Branney, D, Frankham, J, Watters, M, Langton, H, Prout, R, Page, V, Varghes, T, Cowton, A, Kay, A, Potts, K, Birt, M, Kent, M, Wilkinson, A, Jude, E, Turner, V, Savill, H, Mccormick, J, Coulding, M, Siddiqui, S, Mercer, O, Rehman, H, Potla, D, Capps, N, Donaldson, D, Button, H, Martin, T, Hard, K, Agasou, A, Tonks, L, Arden, T, Boyle, P, Carnahan, M, Strickley, J, Adams, C, Childs, D, Rikunenko, R, Leigh, M, Breekes, M, Wilcox, R, Bowes, A, Tiveran, H, Hurford, F, Summers, J, Carter, A, Hussain, Y, Ting, L, Javaid, A, Motherwell, N, Moore, H, Millward, H, Jose, S, Schunki, N, Noakes, A, Clulow, C, Sadera, G, Jacob, R, Jones, C, Blunt, M, Coton, Z, Curgenven, H, S Mohamed Ally, Beaumont, K, Elsaadany, M, Fernandes, K, I Ali Mohamed Ali, Rangarajan, H, Sarathy, V, Selvanayagam, S, Vedage, D, White, M, Smith, M, Truman, N, Chukkambotla, S, Keith, S, Cockerill-Taylor, J, Ryan-Smith, J, Bolton, R, Springle, P, Dykes, J, Thomas, J, Khan, M, T Hijazi, M, Massey, E, Croston, G, Reschreiter, H, Camsooksai, J, Patch, S, Jenkins, S, Humphrey, C, Wadams, B, Bhatia, N, Msiska, M, Adanini, O, Attwood, B, Parsons, P, Tatham, K, Jhanji, S, Black, E, A Dela Rosa, Howle, R, Thomas, B, Bemand, T, Raobaikady, R, Saha, R, Staines, N, Daniel, A, Finn, J, Hutter, J, Doble, P, Shovelton, C, Pawley, C, Kannan, T, Hill, M, Combes, E, Monnery, S, Joefield, T, Popescu, M, Thankachen, M, Oblak, M, Little, J, Mcivor, S, Brady, A, Whittle, H, Prady, H, Chan, R, Ahmed, A, Morris, A, Gibson, C, Gordon, E, Keenan, S, Quinn, H, Benyon, S, Marriott, S, Zitter, L, Park, L, Baines, K, Lyons, M, Holland, M, Keenan, N, Young, M, Garrioch, S, Dawson, J, Tolson, M, Scholefield, B, R, Bi, Richardson, N, Schumacher, N, Cosier, T, Millen, G, Higham, A, Turki, S, Allen, L, Crisp, N, Hazleton, T, Knight, A, Deery, J, Price, C, Turney, S, Tilbey, S, Beranova, E, Wright, D, Georg, L, Twiss, S, Wadd, S, Postlethwaite, K, Gondo, P, Masunda, B, Kayani, A, Hadebe, B, Whiteside, J, Clarke, N, Donnison, P, Trim, F, Leadbitter, I, Butcher, D, O'Sullivan, S, Purewal, B, Bell, S, Rivers', V, O'Leary, R, Birch, J, Collins, E, Anderson, S, Hammerton, K, Andrews, E, Burns, K, Edmond, I, Todd, A, Donnachie, J, Turner, P, Prentice, L, Symon, L, Runciman, N, Auld, F, Halkes, M, Mercer, P, Thornton, L, Debreceni, G, Wilkins, J, Brown, A, Crickmore, V, Subramanian, G, Marshall, R, Jennings, C, Latif, M, Bunni, L, Spivey, M, Bean, S, Burt, K, Linnett, V, Ritzema, J, Sanderson, A, Mccormick, W, Bokhari, M, Kapoor, R, Loader, D, Ayers, A, Harrison, W, North, J, Belagodu, Z, Parasomthy, R, Olufuwa, O, Gherman, A, Fuller, B, Stuart, C, Kelsall, O, Davis, C, Wild, L, Wood, H, Thrush, J, Durie, A, Austin', K, Archer, K, Anderson, P, Vigurs, C, Thorpe, C, Knights, E, Boyle, N, Price, A, Kubisz-Pudelko, A, Wood, D, Lewis, A, Board, S, Pippard, L, Perry, J, Beesley, K, Rattray, A, Lee, E, Lennon, L, Douglas, K, Bell, D, Boyle, R, Glass, L, M Nauman Akhtar, Dent, K, Potoczna, D, Pearson, S, Horsley, E, Spencer, S, Mullan, D, Skinner, D, Gaylard, J, Ortiz-Ruizdegordoa, L, Barber, R, Hewitt, C, Hilldrith, A, Shepardson, S, Wills, M, Jackson-Lawrence, K, Gupta, A, Easthope, A, Timlick, E, Gorman, C, Otaha, I, Gales, A, Coetzee, S, Raj, M, Peiu, M, Quaid, S, Watson, E, Elliott, K, Mallinson, J, Chandler, B, Turnbull, A, Finch, C, Holl, C, Cooper, J, Evans, A, Khaliq, W, Collins, A, E Treus Gude, Love, N, L van Koutrik, Hunt, J, Kaye, D, Fisher, E, Brayne, A, Tuckey, V, Jackson, P, Parkin, J, Raith, E, Tariq, A, Houlden, H, Tucci, A, Hardy, J, Moncur, E, Highgate, J, Cowley, A, Mitra, A, Stead, R, Behan, T, Burnett, C, Newton, M, Heeney, E, Pollard, R, Hatton, J, Patel, A, Kasipandian, V, Allibone, S, M Genetu, R, Otahal, I, O'Brien, L, Omar, Z, Perkins, E, Davies, K, Tetla, D, Shelley, B, Irvine, V, Williams, S, Williams, P, Goodsell, J, Tutton, R, Bough, L, Winter-Goodwin, B, Kitson, R, Pinnell, J, Wilson, A, Nortcliffe, T, Wood, T, Home, M, Holdroyd, K, Robinson, M, Shaw, R, Greig, J, Brady, M, Haigh, A, Matupe, L, Usher, M, Mellor, S, Dale, S, Gledhill, L, Shaw, L, Turner, G, Kelly, D, Anwar, B, Riley, H, Sturgeon, H, Ali, A, Thomis, L, Melia, D, Dance, A, Hanson, K, Humphreys, S, Frost, I, Gopal, V, Godden, J, Holden, A, Swann, S, Smith, T, Clapham, M, Poultney, U, Harper, R, Rice, P, Reece-Anthony, R, Gurung, B, Moultrie, S, Odam, M, Mayer, A, Bellini, A, Pickard, A, Bryant, J, Roe, N, Sowter, J, Lang, K, Taylor, J, Barry, P, Hobrok, M, Tench, H, Wolf-Roberts, R, Mcguinness, H, Loosley, R, Hawcutt, D, Rad, L, O'Malley, L, Saunderson, P, Seddon, G, Anderson, T, Rogers, N, Ruddy, J, Harkins, M, Beith, C, Mcalpine, A, Ferguson, L, Grant, P, Macfadyen, S, Mclaughlin, M, Baird, T, Rundell, S, Welsh, B, Hamill, R, Fisher, F, Gregory, J, Axel, Schmidt, Kerstin, U Ludwig, Selina, Rolker, Markus, M Nöthen, Julia, Fazaal, Verena, Keitel, Björn, Jensen, Torsten, Feldt, Lisa, Knopp, Julia, Schröder, Carlo, Maj, Fabian, Brand, Marc, M Berger, Thorsten, Brenner, Anke, Hinney, Oliver, Witzke, Robert, Bals, Christian, Herr, Nicole, Ludwig, Jörn, Walter, Jochen, Schneider, Johanna, Erber, Christoph, D Spinner, Clemens, M Wendtner, Christof, Winter, Ulrike, Protzer, Nicolas, Casadei, Stephan, Ossowski, Olaf, H Riess, Eva, C Schulte, J Brent Richards, Guillaume, Butler-Laporte, Mirosław, Kwasniewski, Urszula, Korotko, Karolina, Chwialkowska, Magdalena, Niemira, Jerzy, Jaroszewicz, Barbara, Sobala-Szczygiel, Beata, Puzanowska, Anna, Parfieniuk-Kowerda, Diana, Martonik, Anna, Moniuszko-Malinowska, Sławomir, Pancewicz, Dorota, Zarębska-Michaluk, Krzysztof, Simon, Monika, Pazgan-Simon, Iwona, Mozer-Lisewska, Maciej, Bura, Agnieszka, Adamek, Krzysztof Tomasiewicz Małgorzata Pawłowska, Anna, Piekarska, Aleksandra, Berkan-Kawinska, Andrzej, Horban, Justyna, Kowalska, Regina, Podlasin, Piotr, Wasilewski, Arsalin, Azzadin, Miroslaw, Czuczwar, Slawomir, Czaban, Paweł, Olszewski, Jacek, Bogocz, Magdalena, Ochab, Anna, Kruk, Sandra, Uszok, Agnieszka, Bielska, Anna, Szałkowska, Justyna, Raczkowska, Gabriela, Sokołowska, Joanna, Chorostowska-Wynimko, Aleksandra, Jezela-Stanek, Adriana, Roży, Urszula, Lechowicz, Urszula, Polowianiuk, Kamil, Grubczak, Aleksandra, Starosz, Andrzej, Eljaszewicz, Wiktoria, Izdebska, Adam, Krętowski, Robert, Flisiak, Marcin Moniuszko Malak Abedalthagafi Manal Alaamery, Salam, Massadeh, Mohamed, Fawzy, Hadeel, Albardis, Nora, Aljawini, Moneera, Alsuwailm, Faisal, Almalki, Serghei, Mangul, Junghyun, Jung, Hamdi, Mbarek, Chadi, Saad, Yaser, Al-Sarraj, Wadha, Al-Muftah, Radja, Badji, Asma Al Thani, Said, I Ismail, HGI, WES/WGS Working Group Within the, Consortium, GenOMICC, Study, GEN-COVID Multicenter, Renieri, Alessandra [0000-0002-0846-9220], Apollo - University of Cambridge Repository, NIHR, Fallerini, C, Picchiotti, N, Baldassarri, M, Zguro, K, Daga, S, Fava, F, Benetti, E, Amitrano, S, Bruttini, M, Palmieri, M, Croci, S, Lista, M, Beligni, G, Valentino, F, Meloni, I, Tanfoni, M, Minnai, F, Colombo, F, Cabri, E, Fratelli, M, Gabbi, C, Mantovani, S, Frullanti, E, Gori, M, Crawley, F, Butler-Laporte, G, Richards, B, Zeberg, H, Lipcsey, M, Hultström, M, Ludwig, K, Schulte, E, Pairo-Castineira, E, Baillie, J, Schmidt, A, Frithiof, R, Mari, F, Renieri, A, Furini, S, and Crotti, L

Subjects
Male, Medicin och hälsovetenskap, Linkage disequilibrium, Medizin, severity, Genome-wide association study, Disease, WES/WGS Working Group Within the HGI, Logistic regression, Severity of Illness Index, Medical and Health Sciences, Whole Exome Sequencing, Cohort Studies, 0302 clinical medicine, Lasso (statistics), GEN-COVID Multicenter Study, Germany, 80 and over, Genetics (clinical), Exome sequencing, Original Investigation, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Adult, Aged, COVID-19, Female, Humans, Italy, Middle Aged, Polymorphism, Single Nucleotide, Quebec, SARS-CoV-2, Sweden, United Kingdom, Genetic Predisposition to Disease, Phenotype, Single Nucleotide, covid-19, 1104 Complementary and Alternative Medicine, GenOMICC Consortium, Human, coding variants, Computational biology, Biology, 03 medical and health sciences, Exome Sequencing, Genetics, Polymorphism, Gene, 030304 developmental biology, 0604 Genetics, 1114 Paediatrics and Reproductive Medicine, Cohort Studie, 030217 neurology & neurosurgery, Coding (social sciences)
Abstract

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

Published
2021
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8. The interplay between Th17 and T-regulatory responses as well as adipokines in the progression of non-alcoholic fatty liver disease

Author

Adrian Chabowski, Magdalena Świderska, Jerzy Jaroszewicz, Anna Parfieniuk-Kowerda, Agnieszka Stawicka, and Robert Flisiak

Subjects
Review Paper, Hepatology, business.industry, Hypertriglyceridemia, Fatty liver, NASH, nutritional and metabolic diseases, Adipokine, Inflammation, medicine.disease, digestive system, digestive system diseases, Proinflammatory cytokine, Treg, NAFLD, Immunology, Medicine, Th17, Steatohepatitis, Steatosis, medicine.symptom, Metabolic syndrome, business, adipokines
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease, coupled with metabolic syndrome, which may progress to non-alcoholic steatohepatitis (NASH). Diabetes, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia are considered to be the most common causes leading to the incidence of NAFLD. It is assumed that the accumulation of lipid deposits in hepatocytes leads to production of proinflammatory cytokines that triggers the development of liver inflammation. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in NASH, while T helper type 17 (Th17) might functionally oppose Treg-mediated responses. In addition, important mediators of hepatic steatosis are fatty hormones known as adipokines. We aimed to describe the significance and interaction between Treg and Th17-related cytokines as well as adipokines in pathogenesis and its potential use as biomarkers of NAFLD, especially with respect to progression to NASH.

Published
2017
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9. Review article Immune regulation and viral diversity as correlates of natural and treatment induced immune control in persistent hepatitis B virus (HBV) infection

Author

Anna Parfieniuk-Kowerda, Robert Flisiak, and Jerzy Jaroszewicz

Subjects
CD8+ cells, Hepatology, T cell, hemic and immune systems, chemical and pharmacologic phenomena, Review Article, Biology, Virology, Virus, Proinflammatory cytokine, Treg, Pathogenesis, Immune system, medicine.anatomical_structure, Immunopathology, Immunology, HBV, medicine, Cytotoxic T cell, chronic hepatitis B, Th17, CD8
Abstract

In long-lasting chronic hepatitis B, the phenomenon of cytotoxic CD8 T lymphocytes (CTL) exhaustion and unresponsiveness to HBV-specific stimuli was shown to be crucial for the loss of immune control of the virus and disease activity. There is evidence that Tregs, Th17 cells and Bregs seem to be important in pathogenesis of the immunological dysfunction and loss of HBV-specific activity of cytotoxic CD8 T-cells. Th17-driven immune response was shown to be important in pathogenesis of acute HBV infection and exacerbated chronic hepatitis B along with Th1 response contributing to hepatocellular damage due to proinflammatory activities of Th17-derived cytokines, mainly IL-17A. Treg cell responses may be either beneficial or harmful in HBV infection by limiting liver immunopathology or suppressing protective T cell responses, thus promoting virus replication and survival. Thus, Treg/Th17 equilibrium seems to be crucial for the outcomes of HBV infection.

Published
2015
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10. Occurrence and clinical characteristics of hepatocellular carcinoma in the north-eastern Poland

Author

Paweł, Kozłowski, Anna, Parfieniuk-Kowerda, Aleksander, Tarasik, Marcin, Januszkiewicz, Agnieszka, Czauż-Andrzejuk, Tadeusz wojciech, Łapiński, and Robert, Flisiak

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancerrelated mortality worldwide. Risk factors for this malignancy include liver cirrhosis, HBV or HCV infection, fatty liver disease.This study aims to assess the occurrence and clinical characteristics of HCC in the Northeastern Poland between 2011 and 2015. The number of primary lesions, their size and location within the liver were analysed. The risk factors for this cancer in studied population have been identified. The usefulness of AFP screening and imaging studies for the diagnosis of HCC were assessed. A preliminary analysis of the efficacy of anti-tumour therapy was performed.Sixty-seven patients (28% female and 72% male) with diagnosed HCC were enrolled. HCC diagnosis was established according to the criteria proposed by the International Consensus Group for Hepatocellular Neoplasia. Of the 67 patients in the study, 7 (10%) were aged 30 to 50 years and 60 patients (90%) were aged 51 years and older. During the period 2011-2015, an increase in HCC incidence was observed. In studied group the most prevalent (31%) were patients with 2 tumours localised in the 6th, 7th or 8th segments of the liver. Metastatic tumours were present in 15% and portal vein thrombosis in 9% of patients. Risk factors assessment revealed that in 72% of patients HCC coexisted with cirrhosis, 33% of patients were HCV-infected, 30% had HBV infection, and 15% were diagnosed with NASH. Elevated serum AFP level was observed in 83% of patients with liver cirrhosis, and in 58% of patients without cirrhosis (p0.05). Liver transplantation was the best therapeutic option. The efficacy of ablation/resection in combination with sorafenib vs. ablation/partial resection was comparable.There has been an increase in the number of HCC cases in North-eastern Poland in last few years. HCC is more common in men aged 50 years and older. Increased serum AFP level is a useful marker for the diagnosis and monitoring of HCC treatment in patients with liver cirrhosis.

Published
2017

11. Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease

Author

Magdalena Swiderska, Anna Parfieniuk-Kowerda, Tadeusz Wojciech Lapiński, Robert Flisiak, Jerzy Jaroszewicz, and Tomasz Szulzyk

Subjects
0301 basic medicine, Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Anti-nuclear antibody, Hepatitis C virus, Alcoholic hepatitis, Autoimmunity, Enzyme-Linked Immunosorbent Assay, medicine.disease_cause, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, Liver disease, Young Adult, Liver Function Tests, Internal medicine, medicine, Humans, Interleukin 6, Liver Diseases, Alcoholic, Aged, Autoantibodies, Aged, 80 and over, biology, medicine.diagnostic_test, business.industry, Interleukin, Middle Aged, Th1 Cells, medicine.disease, 030104 developmental biology, Liver, Case-Control Studies, biology.protein, Cytokines, Female, business, Liver function tests, Biomarkers
Abstract

Background & Aims: Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver-specific autoantibodies and degree of liver damage.Methods: Ninety-five patients with ALD were enrolled. Serum concentrations of IL-17F, IL-17A, IL-22 were assessed by ELISA. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin and anti-myosin in serum was assessed by immunoblotting, ANA antibodies were detected by ELISA. The results were analysed with regard to the degree of hepatic damage.Results: Serum IL-17F was significantly elevated in ALD patients compared to controls (p=0.03). There was a correlation between serum IL-17F and degree of liver failure evaluated by the MELD score (rs=0.23, p=0.03). Serum IL-22 also correlated with MELD score (rs=0.32, p=0.007) and CTP score (rs=0.28, p=0.02). Anti-F-actin antibodies were present in 19% and ANA-antibodies in 11% of the patients in the study group, and in no subjects in the control group. The prevalence of anti-F-actin autoantibodies was higher in subjects with more advanced liver diseases but also independently associated with IL-17A in the regression analysis. Furthermore, serum IL-22 in anti-F-actin(+)-patients was significantly higher compared to anti-F-actin(-)-patients (p=0.03).Conclusions: Elevation of serum IL-17A, IL-17F, IL-22 correlated with the progression of liver damage and also with presence of F-actin in ALD. Alcoholic liver disease may trigger autoimmunity and formation of autoantibodies, especially anti-F-actin, with possible engagement of Th17-related cytokines in this process.Abbreviations: AA: acetaldehyde; Abs: antibodies; AFP: α-fetoprotein; ALD: alcoholic liver disease; ALT: alanine aminotransferase; AMA-M2: antimitochondrial antibodies; ANA: antinuclear antibodies; ASMA: anti-smooth muscle antibodies; α-SMA: alpha smooth muscle actin; CTP Score: Child-Turcotte-Pugh Score; GAHS: Glasgow Alcoholic Hepatitis Score; GGT: γ-glutamyl transpeptidase; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; HSCs: hepatic stellate cells; IL-β1: interleukin β1; IL-6: interleukin 6; IL-17A: interleukin 17A; IL-17F: interleukin 17F; IL-22: interleukin 22; KCs: Kupffer cells; LC1: liver cytosol antigen type 1; LKM-1: liver kidney microsomal antigen; MA: malondialdehyde; MELD: Model of End-Stage Liver Disease; NASH: non-alcoholic steatoheptatitis; SLA/LP: soluble liver antigen/liver-pancreas; TGF-β: tumour growth factor β; TNF-α: tumour necrosis factor α.

Published
2017

13. Ombitasvir/paritaprevir/ritonavir plus dasabuvir combination in the treatment of chronic HCV infection

Author

Anna Parfieniuk-Kowerda, Mariusz Łucejko, and Robert Flisiak

Subjects
Cyclopropanes, medicine.medical_specialty, Macrocyclic Compounds, Proline, Lactams, Macrocyclic, Pharmacology, Gastroenterology, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Ombitasvir/paritaprevir/ritonavir, 2-Naphthylamine, medicine, Humans, Pharmacology (medical), Anilides, 030212 general & internal medicine, Uracil, Sulfonamides, Dasabuvir, Ritonavir, business.industry, Ribavirin, Valine, General Medicine, Hepatitis C, Chronic, medicine.disease, Ombitasvir, Regimen, chemistry, Paritaprevir, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Carbamates, business, Viral hepatitis, medicine.drug
Abstract

Long lasting hepatocytes damage related to HCV infection stimulates liver fibrosis resulting in cirrhosis, hepatic failure and hepatocellular carcinoma. Until 2011 the only therapeutic option was 24-48 weeks of pegylated interferon alfa and ribavirin (RBV) with efficacy of 40-70%. New generation of direct-acting antivirals (DAA), available from 2014, can be combined and improve efficacy above 90% with 12 weeks of treatment.In this article we describe the first registered all-oral regimen consisting of three DAA - ombitasvir (OBV), paritaprevir (PTV) and dasabuvir (DSV) that became available in EU in 2015 to cure patients infected with HCV genotype 1 and 4. We performed a literature search focusing on efficacy and safety data from Phase 1-3 clinical studies and few real-world data.OBV/PTV/r±DSV±RBV provided an opportunity to cure almost all patients including cirrhotics and non-responders to previous therapy. This treatment is currently recommended as a first line regimen. However, there is still a need for real-world data. In coming years this medication will probably be replaced with the next DAA generation with improved characteristics such as a shorter treatment duration, improved safety and resistance profile.

Published
2016

16. Influence of HCV and HIV on development of cryoglobulinemia

Author

Tadeusz Wojciech Lapiński, Anna Parfieniuk-Kowerda, Robert Flisiak, Anna Grzeszczuk, and Magdalena Rogalska-Płońska

Subjects
Adult, Male, Genotype, Hepatitis C virus, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Hepacivirus, medicine.disease_cause, Kidney Function Tests, Young Adult, Liver Function Tests, hemic and lymphatic diseases, Virology, Medicine, Humans, In patient, Aged, business.industry, Histocytochemistry, Liver and kidney, Incidence (epidemiology), Incidence, virus diseases, Alanine Transaminase, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, Cryoglobulinemia, Liver, Molecular Medicine, Female, business
Abstract

Cryoglobulinemic syndrome refers to a systemic inflammatory process that involves small and medium-sized vessels accompanied by multi-organ damage. The aim of the present study was to determine the incidence of cryoglobulinemia among patients infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HCV/HIV co-infection, as well as evaluation of cryoglobulinemia type. The association was evaluated between cryoglobulinemia and clinical symptoms, selected biochemical measures of liver and kidney function, virologic measures, as well as histopathological changes in the liver. One hundred and forty-one patients were enrolled (59 HCV mono-infected, 48 HIV mono-infected, and 34 HCV/HIV co-infected). Cryoglobulinemia was nearly five times less frequent among HIV mono-infected patients (10%) than HCV mono-infected (53%) and HCV/HIV co-infected patients (59%). Cryoglobulinemia was more frequent in patients infected with genotype 1 HCV than genotype 3 (63% vs. 46%, p=0.12). There was a lower incidence of cryoglobulinemia in HIV mono-infected patients treated with antiretroviral drugs (p=0.04). Cryoglobulinemia correlated with ALT activity (p=0.01) and HIV viral load (p0.001). Symptoms were significantly more frequent among cryoglobulinemic patients than those without cryoglobulinemia (38% vs. 9%, p0.001). The most common symptoms related to cryoglobulinemia, regardless of cryoglobulinemia type, were fatigue (38%), arthralgia (20%), polineuropathy (18%), and skin lesions (14%). In conclusion, HCV mono-infection and HCV/HIV co-infection, regardless of HCV genotype, are potent stimulators of cryoglobulinemia, with its symptomatic form occurring in about 40% of cases. Effective antiretroviral therapy seems to be protective against cryoglobulinemia development in HIV mono-infected patients.

Published
2015

17. Prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders

Author

M. Swiderska, A. Grzeszczuk, J. Pogorzelska, M. Rowiński, T.W. Lapinski, Robert Flisiak, M. Maciaszek, Anna Parfieniuk-Kowerda, B. Naumnik, and Jerzy Jaroszewicz

Subjects
Anti hev, Hepatology, biology, business.industry, medicine.medical_treatment, Immunology, biology.protein, Medicine, Immunosuppression, Antibody, business, Virology, Hepatic disorders
Published
2017
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19. HBV mutations associated with lamivudine therapy

Author

Tadeusz Wojciech, Lapiński, Anna, Parfieniuk-Kowerda, Anna, Trzos, Jerzy, Jaroszewicz, Oksana, Kowalczuk, Jacek, Nikliński, and Robert, Flisiak

Subjects
Adult, Male, Hepatitis B virus, Guanine, Hepatitis B Surface Antigens, Adolescent, Gene Products, pol, Genetic Variation, DNA-Directed DNA Polymerase, Cross Reactions, Middle Aged, Viral Load, Antiviral Agents, Young Adult, Hepatitis B, Chronic, Lamivudine, Drug Resistance, Viral, Humans, Point Mutation, Reverse Transcriptase Inhibitors, Female, Hepatitis B e Antigens, Hepatitis B Antibodies, Aged
Abstract

Lamivudine (LMV) is still the most commonly used nucleoside analogue in majority of the world. Its administration rapidly leads to resistance associated with mutations in HBV polymerase. THE AIM of the study was to assess the prevalence, nature and the time of LMV resistant variants appearence during a long term therapy.Study was carried out among 175 chronic hepatitis B patients treated with LMV. HBsAg, HBeAg as well as anti-HBe antibodies were detected by enzyme immunosorbent assay and HBV-DNA quantification was performed by RT-PCR. Mutations in HBV polymerase gen were detected by PCR using specific primers and direct sequencing. Liver biopsies were performed in 138 patients to evaluate grading and staging of chronic hepatitis by Scheuer's classification.Mean pre-treatment viral load was comparable among HBeAg-positive and negative patients (4.24 x 10(8) vs. 1.26 x 10(8) IU/ml). Mutations in HBV polymerase gen were detected in 96 patients. After 5 years of LMV therapy the prevalence of mutations was 51.9% in HBeAg-positive and 56.1% in HBeAg-negative. The most common mutations were observed at position 180, followed by 204, 202, and 169 of HBV polymerase gen. After average treatment period of 25 months in HBeAg-positive and 35 months in HBeAg-negative additional mutation 204 was observed in 81% and 77% respectively.Large majority of patients develop point mutations at positions 180 and 204 of HBV polymerase gene after 2 years of treatment with LMV. These mutations limit the efficacy of LMV but also yield cross-resistance with entecavir.

Published
2014

21. Emerging treatments for hepatitis C

Author

Anna Parfieniuk-Kowerda, Jerzy Jaroszewicz, and Robert Flisiak

Subjects
Simeprevir, medicine.medical_specialty, Cirrhosis, Sofosbuvir, Hepatitis C virus, Hepacivirus, Interferon alpha-2, medicine.disease_cause, Gastroenterology, Antiviral Agents, Polyethylene Glycols, Interferon, Internal medicine, Genotype, Drug Discovery, Ribavirin, medicine, Humans, Pharmacology (medical), Pharmacology, Clinical Trials as Topic, Sulfonamides, business.industry, Interferon-alpha, Hepatitis C, medicine.disease, Recombinant Proteins, Hepatocellular carcinoma, Immunology, Drug Therapy, Combination, business, Uridine Monophosphate, Heterocyclic Compounds, 3-Ring, medicine.drug
Abstract

About 2.35% of the world population can be infected with hepatitis C virus (HCV) responsible for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently available interferon-based medication is successful in up to 75% of the patients infected with HCV genotypes 1, 2 or 3 and lower efficacy in other genotypes. Unfortunately sustained virologic response (SVR) rate in genotype 1 infected non-responders to previous therapy with advanced hepatic fibrosis even after retreatment with the first generation direct acting antivirals (DAA) is about 40% only.The second generation DAA, which have recently been submitted for registration (Sofosbuvir and Simeprevir) still need combination with PegIFNα and RBV in patients infected with HCV genotype 1. There is a need for more effective antiviral therapy for difficult to treat patients who are interferon intolerant, developed liver cirrhosis or non-responders to previous therapies. Therefore, IFN-free regimens are step for future therapies consisting of combinations of novel investigational DAA and host targeting agents.The introduction of novel DAA with a good safety profile and high barrier to resistance can lead to SVR rates exceeding 90% in treatment naïve patients and non-responders to previous therapy infected with different genotypes.

Published
2013

22. Assessment of serum IGF-1 and adipokines related to metabolic dysfunction in HIV-infected adults

Author

Sławomir Lech Czaban, Anna Parfieniuk-Kowerda, Robert Flisiak, Jerzy Jaroszewicz, and Anna Grzeszczuk

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Immunology, Adipokine, HIV Infections, Biochemistry, Young Adult, Insulin resistance, Adipokines, Risk Factors, Diabetes mellitus, Antiretroviral Therapy, Highly Active, medicine, Immunology and Allergy, Chemerin, Humans, Obesity, Insulin-Like Growth Factor I, Nicotinamide Phosphoribosyltransferase, Molecular Biology, Aged, biology, Adiponectin, business.industry, Waist-Hip Ratio, virus diseases, Hematology, Middle Aged, medicine.disease, Hepatitis C, CD4 Lymphocyte Count, biology.protein, Homeostatic model assessment, Cytokines, Intercellular Signaling Peptides and Proteins, Female, Lipodystrophy, Metabolic syndrome, Chemokines, Insulin Resistance, business
Abstract

HIV/HAART associated metabolic syndrome (HAMS) seems to result from direct influence of HIV, adverse effects of combined antiretroviral therapy (cART) and individual genetic predisposition. This study aimed to assess the influence of HIV infection and cART on serum concentration of insulin-like growth factor-1 (IGF-1) and adipokines related to metabolic abnormalities.Seventy-two HIV infected patients including 48 HIV/HCV coinfected were enrolled in this study. Insulin resistance was evaluated by Homeostatic Model Assessment (HOMA) indexes. Serum concentrations of IGF-1, adiponectin, chemerin and visfatin were measured by ELISA.Significant correlation between serum IGF-1 level and CD4 lymphocytes count was demonstrated and the lowest values were observed in subjects with CD4200 cells/μL. Serum concentration of IGF-1 was significantly higher in patients treated with protease inhibitors based regimen compared to non-nucleoside reverse transcriptase inhibitors and healthy subjects. A significant negative correlation between serum concentration of adiponectin and waist-hip ratio as an indicator of central obesity, was found. There were significant positive correlations between serum concentration of chemerin and HOMA1-IR and serum IGF-1 concentration. Serum chemerin was increased in patients with insulin resistance vs. those with preserved insulin sensitivity.According to these results HAMS is associated with insulin resistance and imbalance of adipokines serum concentration, therefore identification of pathways related to HAMS development might be helpful in management of the syndrome. Serum IGF-1 largely depends on level of immunodeficiency in HIV-infection and may provide a link between immune dysfunction and development of HIV-associated lipodystrophy, AIDS wasting syndrome, diabetes and/or cardiovascular diseases in HIV-infected patients.

Published
2013

23. [Occurrence of autoantibodies in patients with alcoholic liver disease]

Author

Tomasz, Szulzyk, Anna, Parfieniuk-Kowerda, Magdalena, Luto, Tadeusz Wojciech, Lapiński, and Robert, Flisiak

Subjects
Adult, Aged, 80 and over, Male, Enzyme-Linked Immunosorbent Assay, Middle Aged, Actins, Autoimmune Diseases, Liver, Case-Control Studies, Humans, Female, Liver Diseases, Alcoholic, Aged, Autoantibodies
Abstract

Autoantigens are present in normal cells and tissues. However, in physiological conditions autoantigens pose no danger due to the phenomenon of immunologic tolerance. The loss of immunologic tolerance and following autoagression could result from the structure changes of autoantigens as an effect of the activity of chemical factors, such as acetaldehyde, which is metabolite of ethanol. The aim of the study was to evaluate of occurrence of autoantibodies in patients with alcoholic liver disease.Ninety-five patients with chronic alcoholic liver disease and 16 healthy controls were enrolled in this study. The presence of autoantibodies against liver proteins were assessed. The occurrence of studied autoantibodies was evaluated with regard to the degree of liver damage. Inclusion criteria were: age over 21 yrs, at least 3-yrs history of alcoholic liver disease, HBV and HCV-negativity, absence of autoimmunological diseases. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, desmin and miozin in serum was assessed by immunoblotting method and ANA by ELISA.Autoantibodies were demonstrated in sera of 33% of patients. Single isolated autoantibodies were present in 24% of patients, whereas 9% of patients have several autoantibodies. The most prevalent were anti-F-actin (19%) and antinuclear antibodies (11%). Occurrence of anti-F-actin antibodies increased with degree of liver damage.Concluding these results suggest that alcohol may contribute to the activation of autoimmune processes, and particularly against contractile filaments of cells for which F-actin antibodies are produced.

Published
2012

24. Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C

Author

Tadeusz Wojciech Lapiński, Magdalena Swiderska, Anna Parfieniuk-Kowerda, Anatol Panasiuk, Jerzy Jaroszewicz, Magdalena Rogalska-Płońska, and Robert Flisiak

Subjects
Adult, Male, medicine.medical_specialty, Alpha interferon, Apoptosis, Enzyme-Linked Immunosorbent Assay, Gastroenterology, Statistics, Nonparametric, Polyethylene Glycols, Cytokeratin, chemistry.chemical_compound, Epitopes, Pegylated interferon, Fibrosis, Internal medicine, Ribavirin, Medicine, Humans, Aged, Analysis of Variance, Hepatology, medicine.diagnostic_test, biology, Keratin-18, business.industry, Cytochrome c, Cytochromes c, Interferon-alpha, Hepatitis C, Chronic, Middle Aged, medicine.disease, Recombinant Proteins, chemistry, Immunology, biology.protein, Female, business, Liver function tests, medicine.drug
Abstract

Background & Aims Cytochrome c (CYC) and M30-neoepitope of cytokeratin-18 (M30-CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30-CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC). Methods Seventy CHC patients were enrolled in this study. Forty five of them completed pegylated interferon plus ribavirin therapy. Histopathological evaluation of hepatic inflammatory activity and fibrosis, as well as blood liver function tests, was performed. Serum concentrations of M30-CK18 and CYC were measured by ELISA. Results Median serum concentration of M30-CK18 was higher in CHC patients [283 U/L] vs. control [113 U/L] (P = 0.0003) and was associated with inflammatory activity and liver fibrosis (P

Published
2012

25. Exacerbation of chronic hepatitis B during chemotherapy due to testicular seminoma

Author

Anna, Parfieniuk-Kowerda, Magdalena, Rogalska-Plonska, Wojciech Tadeusz, Lapinski, and Robert, Flisiak

Subjects
Adult, Male, Hepatitis B, Chronic, Testicular Neoplasms, Humans, Antineoplastic Agents, Virus Activation, Seminoma
Abstract

Chronic hepatitis B is often asymptomatic until it progresses to advanced stage. The natural course of disease includes flares and periods of decreased inflammatory activity. Immune decline status is proven risk factor for exacerbation of viral hepatitis. Anticancer chemotherapy in chronic HBsAg carriers is known to promote viral replication. Return of immunocompetence after withdrawal of immunosuppressant might result in liver damage. We describe case of a patient with chronic HBV infection who developed hepatitis flare subsequently to the cessation of anti-viral treatment and introduction of chemotherapy due to testicular seminoma. Patients with history of HBV infection who receive immunosuppressive treatment are at risk of HBV reactivation or exacerbation of hepatitis. During immunosuppressive treatment enhanced HBV replication and inhibition of CTL without evident liver injury is observed. Restoration of immune system after withdrawal of immunosuppressant allows recognizing increased expression of HBV antigens in hepatocytes. Intensive elimination of infected hepatocytes could occur resulting in liver tissue necrosis, active hepatitis and liver decompensation. It is recommended for HBV infected patients on immunosuppressive treatment to receive antiviral therapy, particularly with the lowest risk for the selection of mutations, regardless the stage of infection.

Published
2012

26. Treatment of chronic hepatitis C in a patient with Fanconi anaemia

Author

Tadeusz Wojciech Łapiński, Anna Parfieniuk-Kowerda, Magdalena Rogalska-Płońska, and Robert Flisiak

Subjects
Adult, Risk, medicine.medical_specialty, Time Factors, Genotype, Malignancy, Gastroenterology, chemistry.chemical_compound, Internal medicine, Granulocyte Colony-Stimulating Factor, Ribavirin, medicine, Humans, Adverse effect, Past medical history, business.industry, Bone marrow failure, Interferon-alpha, General Medicine, Hepatitis C, Chronic, Viral Load, medicine.disease, medicine.anatomical_structure, Fanconi Anemia, Phenotype, Treatment Outcome, chemistry, Hematologic disease, Immunology, Female, Bone marrow, business, Viral load
Abstract

Fanconi anaemia is a rare autosomal recessive disorder with progressive bone marrow failure and predisposition to malignancy. We report a case of a 26-year-old female patient with Fanconi anaemia and severe chronic active hepatitis C virus infection. Her past medical history included treatment with multiple blood transfusions and bone marrow transplantation at the age of 13. The decision to treat the infection was taken, and history of hematologic disease contributed to the introduction of therapy with leukocyte interferon-α n3 and ribavirin combined with a granulocyte - colony stimulating factor. The treatment was well tolerated and after 48 weeks a reduction of the viral load and alanine aminotransferase activity were achieved. No adverse effects on bone marrow functioning were noted.

Published
2011

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