SARS-CoV-2 infection in patients with autoimmune hepatitis

Abstract

Background & aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continues to have a devastating impact across the globe. However, little is known about the disease course in patients with autoimmune hepatitis (AIH).

Methods: Data for patients with AIH and SARS-CoV-2 infection were combined from 3 international reporting registries and outcomes were compared to those in patients with chronic liver disease of other aetiology (non-AIH CLD) and to patients without liver disease (non-CLD).

Results: Between 25^th March and 24^th October 2020, data were collected for 932 patients with CLD and SARS-CoV-2 infection including 70 with autoimmune hepatitis (AIH). Fifty-eight (83%) patients with AIH were taking ≥1 immunosuppressive drug. There were no differences in rates of major outcomes between patients with AIH and non-AIH CLD, including hospitalization (76% vs. 85%; p = 0.06), intensive care unit admission (29% vs. 23%; p = 0.240), and death (23% vs. 20%; p = 0.643). Factors associated with death within the AIH cohort included age (odds ratio [OR] 2.16/10 years; 1.07-3.81), and Child-Pugh class B (OR 42.48; 4.40-409.53), and C (OR 69.30; 2.83-1694.50) cirrhosis, but not use of immunosuppression. Propensity score matched (PSM) analysis comparing patients with AIH with non-AIH CLD demonstrated no increased risk of adverse outcomes including death (+3.2%; -9.2%-15.7%). PSM analysis of patients with AIH vs. non-CLD (n = 769) demonstrated increased risk of hospitalization with AIH (+18.4%; 5.6-31.2%), but equivalent risk of all other outcomes including death (+3.2%; -9.1%-15.6%).

Conclusion: Patients with AIH were not at increased risk of adverse outcomes despite immunosuppressive treatment compared to other causes of CLD and to matched cases without liver disease.

Lay summary: Little is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from 3 large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system.

Keywords: COVID-19; SARS-CoV-2; autoimmune hepatitis; coronavirus; immunosuppression; liver disease.

Graphical abstract

Fig. 1

Total combined submissions of patients with CLD and SARS-CoV-2 infection COVID-Hep/SECURE-Cirrhosis, and R-LIVER registries between 25th March and 24th October 2020 and the number included in final analysis after exclusions.

Fig. 2

Rates of major outcomes in patients with AIH compared to other aetiologies of CLD and mortality between cohorts according to baseline liver disease severity. (A) Rates of major outcomes following SARS-COV-2 infection in patients with AIH compared to patients with non-AIH CLD. The discrepancy between the rates of ICU requirement and ICU admission are accounted for by a proportion of severe cases being deemed inappropriate for ICU admission or due to lack of ICU availability. (B) Comparison of mortality rates following SARS-COV-2 infection between AIH vs. non-AIH CLD separated by baseline liver disease severity: CLD without cirrhosis (9% vs. 7%; p = 0.473), Child-Pugh A (12% vs. 19%; p = 0.746), Child-Pugh B (54% vs. 34%; p = 0.225) Child-Pugh C (50% vs. 52%; p = 1.0). AIH, autoimmune hepatitis; CLD, chronic liver disease; ICU, intensive care unit; RRT, new requirement for renal replacement therapy; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Fig. 3

Propensity score matched analysis of major outcomes for AIH cohort compared with non-AIH CLD cohort and non-CLD cohort. (A) Plot shows propensity-score matched analyses for major outcomes following SARS-CoV-2 infection for AIH compared to non-AIH CLD. Variables selected for propensity score matching were age in years, interactions with age, sex, and baseline liver disease severity (CLD without cirrhosis, CTP-A, CTP-B, CTP-C). Bars represent 95% CIs. The risk of each major outcome between AIH vs. non-AIH CLD was hospitalization -9.7% (95% CI -20.3%–0.7%; p = 0.067), ICU requirement +6.2% (95% CI -0.07%–19.2%; p = 0.349), ICU admission +6.6% (95% CI -5.6%–18.8%; p = 0.289), invasive ventilation -2.9% (95% CI -13.3%–7.6%; p = 0.59, and death (+3.2%; 95% CI -9.2%–15.7%; p = 0.609). (B) Plot shows propensity-score matched analyses for major outcomes following SARS-CoV-2 infection for AIH compared to the non-CLD cohort. Variables selected for propensity score matching were age, interactions with age, sex, hypertension, COPD, heart disease and diabetes. The risk of each major outcome between AIH vs. non-CLD was hospitalization +18.4% (95% CI 5.6–31.2%; p = 0.005), ICU requirement +6.2% (95% CI -6.8%–19.3%; p = 0.349), ICU admission +6.6% (95% CI -5.6%–18.8%; p = 0.289), invasive ventilation -2.9% (95% CI -13.3%–7.5%; p = 0.590), and death +3.2% (95% CI -9.1%-15.6%; p = 0.609). AIH, autoimmune hepatitis; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.