1. Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis
- Author
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George N. Dalekos, Cristina Rigamonti, Godolfino Miranda Zazueta, Ali Rıza Calışkan, Annarosa Floreani, Berat Ebik, Kadri Atay, Aylin Demirezer Bolat, Nazım Ekin, Eric M. Yoshida, Graciela Castro Narro, Fatih Güzelbulut, Murat Biyik, Manuel Mendizabal, Renumathy Dhanasekaran, Stefano Fagiuoli, Thomas D. Schiano, Ellina Lytvyak, Shalom Frager, Nataly Chris Escajadillo Vargas, Yucel Ustundag, Ramazan Idilman, Andreea M. Catana, Alvaro Urzúa, Ahmet Yavuz, Staffan Wahlin, Mesut Aydin, Cumali Efe, Laura Cristoferi, Hatef Massoumi, Maria Vincent, Sandro Ruiz Garcia, Evrim Kahramanoğlu-Aksoy, Natalia Ratusnu, Craig Lammert, Sümeyra Yıldırım, Mário Reis Álvares-da-Silva, Murat Harputoğlu, Marina Silveira, Murat Kiyici, Fátima Higuera-de la Tijera, Nurhan Demir, Cynthia Levy, Einar Bjornsson, Javier Brahm, Rotonya M. Carr, Nidah S. Khakoo, Andres Jose Gomez Aldana, Murat Akyildiz, Leyla Nazal, Alessio Gerussi, Tuğçe Eşkazan, Zeynep Ellik, Pietro Invernizzi, Fulya Gunsar, Ezequiel Ridruejo, Eleonora De Martin, Tugrul Purnak, Fatih Eren, Hüseyin Kaçmaz, Margarita Anders, Nikolaos K. Gatselis, Romee Snijders, Sezgin Barutçu, Costica Aloman, Alexandra Heurgue-Berlot, Bianca Magro, Jonathan Aguirre, Kader Irak, Koray Tascilar, Aldo J. Montano-Loza, Marcelo Silva, David N. Assis, Joost P.H. Drenth, Eira Cerda Reyes, Ibrahim Hatemi, Mirta Peralta, Sanjaya K. Satapathy, James L. Boyer, Yasemin H. Balaban, Efe, C, Lammert, C, Tascilar, K, Dhanasekaran, R, Ebik, B, Higuera-de la Tijera, F, Caliskan, A, Peralta, M, Gerussi, A, Massoumi, H, Catana, A, Purnak, T, Rigamonti, C, Aldana, A, Khakoo, N, Nazal, L, Frager, S, Demir, N, Irak, K, Melekoglu-Ellik, Z, Kacmaz, H, Balaban, Y, Atay, K, Eren, F, Alvares-da-Silva, M, Cristoferi, L, Urzua, A, Eskazan, T, Magro, B, Snijders, R, Barutcu, S, Lytvyak, E, Zazueta, G, Demirezer-Bolat, A, Aydin, M, Heurgue-Berlot, A, De Martin, E, Ekin, N, Yildirim, S, Yavuz, A, Biyik, M, Narro, G, Kiyici, M, Akyildiz, M, Kahramanoglu-Aksoy, E, Vincent, M, Carr, R, Gunsar, F, Reyes, E, Harputluoglu, M, Aloman, C, Gatselis, N, Ustundag, Y, Brahm, J, Vargas, N, Guzelbulut, F, Garcia, S, Aguirre, J, Anders, M, Ratusnu, N, Hatemi, I, Mendizabal, M, Floreani, A, Fagiuoli, S, Silva, M, Idilman, R, Satapathy, S, Silveira, M, Drenth, J, Dalekos, G, Assis, D, Bjornsson, E, Boyer, J, Yoshida, E, Invernizzi, P, Levy, C, Montano-Loza, A, Schiano, T, Ridruejo, E, Wahlin, S, Akyıldız, Murat (ORCID 0000-0002-2080-7528 & YÖK ID 123080), Efe, Cumalı, Lammert, Craig, Taşçılar, Koray, Dhanasekaran, Renumathy, Ebik, Berat, Higuera-de la Tijera, Fatima, Çalışkan, Ali R., Peralta, Mirta, Gerussi, Alessio, Massoumi, Hatef, Catana, Andreea M., Purnak, Tuğrul, Rigamonti, Cristina, Aldana, Andres J. G., Khakoo, Nidah, Nazal, Leyla, Frager, Shalom, Demir, Nurhan, Irak, Kader, Melekoğlu-Ellik, Zeynep, Kaçmaz, Hüseyin, Balaban, Yasemin, Atay, Kadri, Eren, Fatih, Alvares-da-Silva, Mario R., Cristoferi, Laura, Urzua, Alvaro, Eskazan, Tugce, Magro, Bianca, Snijders, Romee, Barutçu, Sezgin, Lytvyak, Ellina, Zazueta, Godolfino M., Demirezer-Bolat, Aylin, Aydın, Mesut, Heurgue-Berlot, Alexandra, De Martin, Eleonora, Ekin, Nazım, Yıldırım, Sumeyra, Yavuz, Ahmet, Bıyık, Murat, Narro, Graciela C., Kıyıcı, Murat, Kahramanoğlu-Aksoy, Evrim, Vincent, Maria, Carr, Rotonya M., Günsar, Fulya, Reyes, Eira C., Harputluoğlu, Murat, Aloman, Costica, Gatselis, Nikolaos K., Üstündağ, Yücel, Brahm, Javier, Vargas, Nataly C. E., Güzelbulut, Fatih, Garcia, Sandro R., Aguirre, Jonathan, Anders, Margarita, Ratusnu, Natalia, Hatemi, İbrahim, Mendizabal, Manuel, Floreani, Annarosa, Fagiuoli, Stefano, Silva, Marcelo, İdilman, Ramazan, Satapathy, Sanjaya K., Silveira, Marina, Drenth, Joost P. H., Dalekos, George N., Assis, David N., Bjornsson, Einar, Boyer, James L., Yoshida, Eric M., Invernizzi, Pietro, Levy, Cynthia, Montano-Loza, Aldo J., Schiano, Thomas D., Ridruejo, Ezequiel, Wahlin, Staffan, and School of Medicine
- Subjects
Adult ,Male ,medicine.medical_specialty ,budesonide ,Cirrhosis ,Adolescent ,Gastroenterology and hepatology ,medicine.medical_treatment ,Azathioprine ,Autoimmune hepatitis ,mercaptopurine ,Liver transplantation ,Gastroenterology ,Young Adult ,Sars-Cov-2 Infection ,Internal medicine ,medicine ,Humans ,Autoimmunity ,Budesonide ,Mercaptopurine ,SARS-CoV-2 ,Aged ,Retrospective Studies ,Mechanical ventilation ,Aged, 80 and over ,azathioprine ,liver transplantation ,Hepatology ,business.industry ,autoimmunity ,COVID-19 ,Immunosuppression ,Odds ratio ,Middle Aged ,medicine.disease ,Tacrolimus ,Liver-Transplant Recipients ,Hospitalization ,Hepatitis, Autoimmune ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Pharmaceutical Preparations ,Female ,business ,medicine.drug - Abstract
Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH., Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic), A. Gerussi, L. Cristoferi, and P. Invernizzi acknowledge that this research was partially supported by the Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).
- Published
- 2021