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

Abstract

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 (SARSCoV2). The following two points should be highlighted: (1) the nonsignificance and magnitude of differences in prognostic outcomes between patients with AIH and patients with nonAIH chronic liver disease (CLD); (2) the potential broader use of tacrolimus in patients with AIH with coronavirus disease 2019 (COVID19). First, patients with AIH had lower rates of overall mortality, severe COVID19, supplemental oxygen use, and hospitalization than patients with nonAIH 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 nonAIH CLD etiologies. Regarding (1), 80% of the AIH cohort were female; however, male patients with COVID19 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 nonAIH CLD cohort were not disclosed. Moreover, the pathophysiological similarities between AIH and the major etiologies of nonAIH CLD may lead to nonsignificance in outcomes. According to Marjot and colleagues,(3) alcoholic liver disease (ALD) and metabolicassociated fatty liver disease (MAFLD) were the most common etiologies in the nonAIH CLD cohort. While AIH is pathophysiologically defined as autoantibodydriven hepatic inflammation, ALD increases inflammation through hepatocyte death and increased microbial autotransplantation by elevated intestinal permeability.(4) In MAFLD, lipid overflowinduced mitochondrial dysfunction and enhanced oxidative stress induce lipoapoptosis, leading to hepatic inflammation.(5) Also, patients with nonAIH CLD might be treated with immunosuppressive agents (e.g., steroids) to avoid hyperinflammation in severe COVID19. Most patients with AIH also maintained immunosuppressive therapy during COVID19 (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 COVID19. Secondly, tacrolimus can potentially be used for immunosuppression in patients with AIH with COVID19. AIH is largely treated by corticosteroids and azathioprine. In a realworldexperience study, over half of patients with AIH who used calcineurin inhibitor as secondline/thirdline therapy (due to azathioprine/steroid intolerance or incomplete response) achieved normalization of serum aminotransferases.(6) Because tacrolimus shows protection against COVID19, 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 COVID19.