Letter to the Editor: Autoimmune Hepatitis and Coronavirus Disease 2019: Disease Outcomes and Tacrolimus Use

TO THE EDITOR:

I welcome the results reported by Efe and colleagues.^{( 1 )} This study broadens our understanding regarding the prognostic outcomes and disease severity of patients with autoimmune hepatitis (AIH) infected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The following two points should be highlighted: (1) the nonsignificance and magnitude of differences in prognostic outcomes between patients with AIH and patients with non‐AIH chronic liver disease (CLD); (2) the potential broader use of tacrolimus in patients with AIH with coronavirus disease 2019 (COVID‐19).

First, patients with AIH had lower rates of overall mortality, severe COVID‐19, supplemental oxygen use, and hospitalization than patients with non‐AIH CLD. These correlations were nonsignificant. This might be attributable to either (1) the inclusion of predominantly female subjects in the AIH cohort and/or (2) the pathophysiological similarities between AIH and major non‐AIH CLD etiologies. Regarding (1), 80% of the AIH cohort were female; however, male patients with COVID‐19 were more prone to intensive care unit admission and death.^{( 2 )} The predominance of female subjects in the cohort may have contributed to better clinical outcomes; unfortunately, this cannot be confirmed because anthropometric characteristics of the non‐AIH CLD cohort were not disclosed.

Moreover, the pathophysiological similarities between AIH and the major etiologies of non‐AIH CLD may lead to nonsignificance in outcomes. According to Marjot and colleagues,^{( 3 )} alcoholic liver disease (ALD) and metabolic‐associated fatty liver disease (MAFLD) were the most common etiologies in the non‐AIH CLD cohort. While AIH is pathophysiologically defined as autoantibody‐driven hepatic inflammation, ALD increases inflammation through hepatocyte death and increased microbial autotransplantation by elevated intestinal permeability.^{( 4 )} In MAFLD, lipid overflow‐induced mitochondrial dysfunction and enhanced oxidative stress induce lipoapoptosis, leading to hepatic inflammation.^{( 5 )} Also, patients with non‐AIH CLD might be treated with immunosuppressive agents (e.g., steroids) to avoid hyperinflammation in severe COVID‐19. Most patients with AIH also maintained immunosuppressive therapy during COVID‐19 (62.7%). Thus, the nonsignificant difference in survival outcomes between the two groups can be explained by the attainment of similar levels of immunosuppression during COVID‐19.

Secondly, tacrolimus can potentially be used for immunosuppression in patients with AIH with COVID‐19. AIH is largely treated by corticosteroids and azathioprine. In a real‐world‐experience study, over half of patients with AIH who used calcineurin inhibitor as second‐line/third‐line therapy (due to azathioprine/steroid intolerance or incomplete response) achieved normalization of serum aminotransferases.^{( 6 )} Because tacrolimus shows protection against COVID‐19, its use in patients with AIH might be encouraged. Unfortunately, only 5 patients in this study used tacrolimus (none used tacrolimus monotherapy). More studies are required to analyze the clinical relevance of tacrolimus in patients with AIH with COVID‐19.