S2380 Association Between Prior COVID-19 Infection and New Diagnoses of Autoimmune Liver Diseases: A Retrospective Case-Control Study

Introduction: Previous studies have identified SARS-CoV-2 as a possible trigger for autoimmunity through immune system hyperstimulation and molecular mimicry. Therefore, 1 potential complication of COVID-19 is the development of autoimmune diseases, including primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and IgG4-related hepatobiliary disease (IgG4-HD). Establishing COVID-19 as a risk factor for these conditions could have significant clinical implications, especially if the incidence of these diseases rises in the post-pandemic era. This study aims to determine whether prior COVID-19 positivity is associated with new diagnoses of autoimmune liver diseases. Methods: A retrospective case-control study was conducted using the electronic medical records of a large community-based healthcare system in Illinois and Wisconsin. Patients with International Classification of Diseases, Tenth Revision codes for PSC, PBC, AIH, and IgG4-HD who sought care between January 2020 and January 2023 were identified. Manual chart review confirmed diagnoses based on clinical, serologic, and/or histologic findings and verified COVID-19 testing status by PCR in a healthcare setting. Cases were matched 1:1 to controls by age, sex, and race, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Of 2,739 patients identified, 434 met inclusion criteria after manual review (188 PBC, 61 PSC, 162 AIH, 8 IgG4-HD, 13 PBC-AIH overlap, 2 PSC-AIH overlap). Among patients who had COVID-19 prior to diagnosis, the median time from infection to liver disease diagnosis was 11.2 months (range 0.37–26.6 months). The OR for any autoimmune liver disease following a positive COVID-19 test was 1.94 (95% CI 1.17–3.22, P = 0.01). ORs for PSC, AIH, and PBC were 1.85 (95% CI 0.51–6.67, P = 0.34), 1.99 (95% CI 0.86–4.61, P = 0.10), and 1.70 (95% CI 0.78–3.71, P = 0.18), respectively. Due to small sample sizes, ORs for overlap syndromes and IgG4-HD were not calculated. Conclusion: Although individual autoimmune liver diseases did not reach statistical significance, the statistically significant association observed when these diseases were considered as a group suggests a possible shared immune-mediated mechanism following COVID-19 infection. These findings do not establish a causal relationship between COVID-19 and PSC, PBC, or AIH individually. However, the observed association, combined with biologically plausible mechanisms, supports the need for larger, multicenter studies to further investigate this potential link.