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

Cumali Efe; Craig Lammert; Koray Taşçılar; Renumathy Dhanasekaran; Berat Ebik; Fatima Higuera-de la Tijera; Ali R. Calışkan; Mirta Peralta; Alessio Gerussi; Hatef Massoumi; Andreea M. Catana; Tugrul Purnak; Cristina Rigamonti; Andres J. G. Aldana; Nidah Khakoo; Leyla Nazal; Shalom Frager; Nurhan Demir; Kader Irak; Zeynep Melekoğlu-Ellik; Hüseyin Kacmaz; Yasemin Balaban; Kadri Atay; Fatih Eren; Mario R. Alvares-da-Silva; Laura Cristoferi; Álvaro Urzua; Tuğçe Eşkazan; Bianca Magro; Romee Snijders; Sezgin Barutçu; Ellina Lytvyak; Godolfino M. Zazueta; Aylin Demirezer-Bolat; Mesut Aydın; Alexandra Heurgue-Berlot; Eleonora De Martin; Nazım Ekin; Sümeyra Yıldırım; Ahmet Yavuz; Murat Bıyık; Graciela C. Narro; Murat Kıyıcı; Murat Akyıldız; Evrim Kahramanoğlu-Aksoy; Maria Vincent; Rotonya M Carr; Fulya Günşar; Eira C. Reyes; Murat Harputluoğlu; Costica Aloman; Nikolaos K. Gatselis; Yücel Üstündağ; Javier Brahm; Nataly C. E. Vargas; Fatih Güzelbulut; Sandro R. Garcia; Jonathan Aguirre; Margarita Anders; Natalia Ratusnu; Ibrahim Hatemi; Manuel Mendizabal; Annarosa Floreani; Stefano Fagiuoli; Marcelo Silva; Ramazan Idilman; Sanjaya K. Satapathy; Marina Silveira; Joost P. H. Drenth; George N Dalekos; David N.Assis; Einar Björnsson; James L. Boyer; Eric M. Yoshida; Pietro Invernizzi; Cynthia Levy; Aldo J. Montano-Loza; Thomas D. Schiano; Ezequiel Ridruejo; Staffan Wahlin

Disclosures

Liver International. 2022;42(3):607-614. 

In This Article

Abstract and Introduction

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.

Introduction

Coronavirus Disease 2019 (COVID-19) has rapidly spread worldwide causing an ongoing pandemic since December 2019. The majority of COVID-19 cases have mild symptoms while individuals with older age and co-morbid conditions such as cardiovascular diseases, chronic lung/kidney diseases and diabetes mellitus are at increased risk of severe COVID-19 outcomes.[1,2] The liver is also commonly affected by COVID-19[3,4] and patients with underlying chronic liver diseases have high rates of hospitalization and death.

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease treated by immunosuppressive therapy. Approximately, 80% of AIH patients respond to standard therapy (glucocorticoids and/or thiopurines). Mycophenolate mofetil (MMF) and tacrolimus are alternative immunosuppressive drugs for patients who do not respond or are intolerant to standard therapy.[5,6] Some studies have suggested that baseline therapy with glucocorticoids and thiopurines is associated with an increased risk of severe COVID-19 for patients with inflammatory bowel diseases (IBD) or rheumatic disorders.[7–9] On the other hand, baseline use of tacrolimus was associated with a better COVID-19 outcome while MMF was linked to severe COVID-19 in liver transplant recipients.[10,11]

Data regarding the clinical presentation and outcome of COVID-19 in AIH patients are limited to two international registry studies, and a retrospective case study.[12–14] These studies suggested that the continuation of immunosuppressive therapy during COVID-19 infection was not associated with adverse outcomes in AIH.

In our previous study,[13] we described factors that were associated with severe COVID-19 outcome in patients with AIH. Because of sample size limitations, we could not fully evaluate any potential impact of baseline AIH medications on COVID-19 course. We have extended our data and now aim to explore the impact of AIH medications, including glucocorticoids, thiopurines, MMF and tacrolimus, on the risk of worse COVID-19 severity.

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