Liver Injury in Patients Hospitalized with Coronavirus Disease 2019 Correlates with Hyperinflammatory Response and Elevated Interleukin-6

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1β). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1β. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.