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. 2022 Mar;42(3):607-614.
doi: 10.1111/liv.15121. Epub 2021 Dec 13.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Cumali Efe  1 , Craig Lammert  2 , Koray Taşçılar  3 , Renumathy Dhanasekaran  4 , Berat Ebik  5 , Fatima Higuera-de la Tijera  6 , Ali R Calışkan  7 , Mirta Peralta  8   9 , Alessio Gerussi  10   11 , Hatef Massoumi  12 , Andreea M Catana  13 , Tugrul Purnak  14 , Cristina Rigamonti  15   16 , Andres J G Aldana  17 , Nidah Khakoo  18 , Leyla Nazal  19 , Shalom Frager  12 , Nurhan Demir  20 , Kader Irak  21 , Zeynep Melekoğlu-Ellik  22 , Hüseyin Kacmaz  7 , Yasemin Balaban  23 , Kadri Atay  24 , Fatih Eren  25 , Mario R Alvares-da-Silva  26   27 , Laura Cristoferi  10   11 , Álvaro Urzua  28 , Tuğçe Eşkazan  29 , Bianca Magro  30 , Romee Snijders  31   32 , Sezgin Barutçu  33 , Ellina Lytvyak  34 , Godolfino M Zazueta  35 , Aylin Demirezer-Bolat  36 , Mesut Aydın  37 , Alexandra Heurgue-Berlot  38 , Eleonora De Martin  39 , Nazım Ekin  5 , Sümeyra Yıldırım  40 , Ahmet Yavuz  41 , Murat Bıyık  41 , Graciela C Narro  35 , Murat Kıyıcı  42 , Murat Akyıldız  43 , Evrim Kahramanoğlu-Aksoy  44 , Maria Vincent  45 , Rotonya M Carr  46 , Fulya Günşar  47 , Eira C Reyes  48 , Murat Harputluoğlu  49 , Costica Aloman  50 , Nikolaos K Gatselis  51 , Yücel Üstündağ  52 , Javier Brahm  53 , Nataly C E Vargas  54 , Fatih Güzelbulut  55 , Sandro R Garcia  56 , Jonathan Aguirre  57 , Margarita Anders  58 , Natalia Ratusnu  59 , Ibrahim Hatemi  29 , Manuel Mendizabal  9   60 , Annarosa Floreani  61   62 , Stefano Fagiuoli  30 , Marcelo Silva  9   60 , Ramazan Idilman  22 , Sanjaya K Satapathy  45 , Marina Silveira  63 , Joost P H Drenth  31   32 , George N Dalekos  51 , David N Assis  63 , Einar Björnsson  64 , James L Boyer  63 , Eric M Yoshida  65 , Pietro Invernizzi  10   11 , Cynthia Levy  18 , Aldo J Montano-Loza  34 , Thomas D Schiano  66 , Ezequiel Ridruejo  9   60   67 , Staffan Wahlin  68
Affiliations

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Cumali Efe et al. Liver Int. 2022 Mar.

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.

Keywords: SARS-CoV-2; autoimmunity; azathioprine; budesonide; liver transplantation; mercaptopurine.

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