Effects of Immunosuppressive Drugs on COVID-19 Severity in Patients With Autoimmune Hepatitis

Abbreviations: AZA, azathioprine; MMF, mycophenolate mofetil; 6-MP, mercaptopurine; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis.

Note: Odds ratios are from an ordinal logistic regression model and indicate the relative risk of being in a worse outcome category compared to no treatment. In the fully adjusted model, additional adjustments were made for the number of comorbidities (Table 1), presence of cirrhosis and combinations of treatment.

Authors and Disclosures

Cumali Efe¹, Craig Lammert², Koray Taşçılar³, Renumathy Dhanasekaran⁴, Berat Ebik⁵, Fatima Higuera-de la Tijera⁶, Ali R. Calışkan⁷, Mirta Peralta^8,9, Alessio Gerussi^10,11, Hatef Massoumi¹², Andreea M. Catana¹³, Tugrul Purnak¹⁴, Cristina Rigamonti^15,16, Andres J. G. Aldana¹⁷, Nidah Khakoo¹⁸, Leyla Nazal¹⁹, Shalom Frager¹², Nurhan Demir²⁰, Kader Irak²¹, Zeynep Melekoğlu-Ellik²², Hüseyin Kacmaz⁷, Yasemin Balaban²³, Kadri Atay²⁴, Fatih Eren²⁵, Mario R. Alvares-da-Silva^26,27, Laura Cristoferi^10,11, Álvaro Urzua²⁸, Tuğçe Eşkazan²⁹, Bianca Magro³⁰, Romee Snijders^31,32, Sezgin Barutçu³³, Ellina Lytvyak³⁴, Godolfino M. Zazueta³⁵, Aylin Demirezer-Bolat³⁶, Mesut Aydın³⁷, Alexandra Heurgue-Berlot³⁸, Eleonora De Martin³⁹, Nazım Ekin⁵, Sümeyra Yıldırım⁴⁰, Ahmet Yavuz⁴¹, Murat Bıyık⁴¹, Graciela C. Narro⁴², Murat Kıyıcı⁴³, Murat Akyıldız⁴⁴, Evrim Kahramanoğlu-Aksoy⁴⁵, Maria Vincent⁴⁶, Rotonya M Carr⁴⁷, Fulya Günşar⁴⁸, Eira C. Reyes⁴⁹, Murat Harputluoğlu⁵⁰, Costica Aloman⁵¹, Nikolaos K. Gatselis⁵², Yücel Üstündağ⁵³, Javier Brahm⁵⁴, Nataly C. E. Vargas⁵⁵, Fatih Güzelbulut⁵⁶, Sandro R. Garcia⁵⁷, Jonathan Aguirre⁵⁸, Margarita Anders⁵⁹, Natalia Ratusnu⁶⁰, Ibrahim Hatemi²⁹, Manuel Mendizabal^9,61, Annarosa Floreani^62,63, Stefano Fagiuoli³⁰, Marcelo Silva^9,61, Ramazan Idilman²², Sanjaya K. Satapathy⁴⁶, Marina Silveira⁶⁴, Joost P. H. Drenth^31,32, George N Dalekos⁵², David N.Assis⁶⁴, Einar Björnsson⁶⁵, James L. Boyer⁶⁴, Eric M. Yoshida⁶⁶, Pietro Invernizzi^10,11, Cynthia Levy¹⁸, Aldo J. Montano-Loza³⁴, Thomas D. Schiano⁶⁷, Ezequiel Ridruejo^9,61,68 and Staffan Wahlin<sup>69

1</sup>Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey
²Department of Medicine Indiana, University School of Medicine Indianapolis, Indianapolis, Indiana, USA
³Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
⁴Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
⁵Department of Gastroenterology, Gazi Yaşargil Education and Research Hospital, Diyarbakir, Turkey
⁶Gastroenterology and Hepatology Unit, Hospital General de México, Ciudad de México, México
⁷Department of Gastroenterology, Adıyaman University, Adıyaman, Turkey
⁸Hepatology Section, Hospital Francisco J Muñiz, Ciudad Autónoma de Buenos Aires, Argentina
⁹Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Argentina
¹⁰Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
¹¹European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
¹²Department of Medicine, Montefiore Medical Center, Bronx, New York, USA
¹³Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
¹⁴Division of Gastroenterology, Hepatology and Nutrition, McGovern Medical School, Houston, Texas, USA
¹⁵Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
¹⁶Division of Internal Medicine, "AOU Maggiore della Carità", Novara, Italy
¹⁷Gastroenterology and Hepatology Unit, Fundación Santa Fe de Bogotá y universidad de Los Andes, Bogotá, Colombia
¹⁸Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
¹⁹Gastroenterology and Hepatology Unit, Clínica Las Condes, Santiago de Chile, Chile
²⁰Department of Gastroenterology, Haseki Training and Research Hospital, Istanbul, Turkey
²¹Department of Gastroenterology, SBU Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey
²²Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
²³Department of Gastroenterology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
²⁴Departmant of Gastroenterology, Mardin State Hospital, Mardin, Turkey
²⁵Departmant of Gastroenterology, Ordu State Hospital, Ordu, Turkey
²⁶Gastroenterology and Hepatology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
²⁷Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
²⁸Gastroenterology and Hepatology Unit. Hospital Clínico, Universidad de Chile, Santiago de Chile, Chile
²⁹Department of Gastroenterology, Cerrahpaşa School of Medicine, İstanbul, Turkey
³⁰Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII-Bergamo, Bergamo, Italy
³¹Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
³²European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Nijmegen, The Netherlands
³³Department of Gastroenterology, University of Gaziantep Medical Faculty, Gaziantep, Turkey
³⁴Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
³⁵Gastroenterology Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
³⁶Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
³⁷School of Medicine, Department of Gastroenterology, Van Yuzuncu Yil University, Van, Turkey
³⁸Department of Hepato-Gastroenterology, CHU Reims, Reims, France
³⁹Centre Hepato-Biliaire, Hôpital Paul-Brousse, FHU Hepatinov, INSERM Unit UMR 1193, Univ Paris-Saclay, Gif-sur-Yvette, France
⁴⁰Department of Gastroenterology, Erciyes Hospital, Kayseri, Turkey
⁴¹Division of Gastroenterology, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey
⁴²Gastroenterology Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
⁴³Department of Gastroenterology, Medical Faculty, Uludag University, Bursa, Turkey
⁴⁴Department of Gastroenterology, Koc University School of Medicine, Istanbul, Turkey
⁴⁵Department of Gastroenterology, Keçiören Training and Research Hospital, Ankara, Turkey
⁴⁶Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY, USA
⁴⁷Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
⁴⁸Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
⁴⁹Hepatology Unit. Hospital Militar Central de México, Ciudad de México, México
⁵⁰Department of Gastroenterology, Inönü University School of Medicine, Malatya, Turkey
⁵¹Section of Hepatology, Rush University Medical Center, Chicago, Illinois, USA
⁵²Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
⁵³Department of Gastroenterology, Bulent Ecevit University of Medicine, Zonguldak, Turkey
⁵⁴Gastroenterology Unit, Clínica Las Condes, Santiago, Chile
⁵⁵Hepatology Unit Hospital Nacional Almanzor Aguinaga Asenjo, Chiclayo, Perú
⁵⁶Department of Gastroenterology, Haydarpaşa Numune Education and Research Hospital, İstanbul, Turkey
⁵⁷Gastroenterology Unit, Hospital Víctor Lazarte Echegaray, Trujillo, Perú
⁵⁸Hepatology Unit, Hospital Ángeles Pedregal, Ciudad de México, México
⁵⁹Hepatology and Liver Transplant Unit, Hospital Alemán, Buenos Aires, Argentina
⁶⁰Hepatology Unit, Hospital Regional de Ushuaia, Ushuaia, Argentina
⁶¹Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
⁶²Scientific Consultant IRCCS Negrar, Verona, Italy
⁶³Senior Scholar, University of Padova, Padova, Italy
⁶⁴Department of Medicine, Section of Digestive Diseases Yale School of Medicine, New Haven, Connecticut, USA
⁶⁵Department of Internal Medicine, Section of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
⁶⁶Division of Gastroenterology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada
⁶⁷Division of Liver Diseases, The Mount Sinai Medical Center, New York, New York, USA
⁶⁸Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas, CEMIC, Ciudad Autónoma de Buenos Aires, Argentina
⁶⁹Hepatology Division, Department of Upper GI Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

Correspondence
Cumali Efe MD, Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey. Email: drcumi21@hotmail.com

Conflict of Interest
The authors do not have any disclosures to report.

Author Contributions
CE, SW, TDS, RD and ER conceptualized the study. CE, RD, BE, KT, SW and ER collected and analysed data. CE, RD, CL, BE, FHT, CA, ARÇ, MP, LC, HM, MAC, TP, CR, AJGA, NK, HK, LN, SF, KI, ZME, MMA, MA, YB, KA, AG, EB, FE, AU, BM, NE, ND, RS, RMC, MH, IH, MK, MM, MS, MRAS, TE, BM, SB, EL, GMZ, ADB, MA, AHB, EDM, SY, AY, MB, GCN, EKA, MV, FG, ECR, NKG, YÜ, JB, NCEV, FGU, SRG, JA, MA, NR, AF, SF, SKS, GND, EMY, RI, MS, JPHD, DA, EB, JLB, PI, CL, ER and SW contributed data. CE, RD, TDS, KT, ER, and SW interpreted data and prepared manuscript. All authors approved the final version of the manuscript.

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Lay Summary

In this large cohort of patients with AIH, baseline treatment with glucocorticoids and thiopurines prior to the onset of COVID-19 was associated with worse COVID-19 severity. Our findings provide data to clinicians for management of AIH patients with COVID-19 and highlight the importance of preventive public health measures for these patients during the COVID-19 pandemic.