Systemic inflammation as fuel for acute liver injury in COVID-19

Abstract

Background: A cytokine storm conceivably contributes to manifestations of corona virus disease (COVID-19). Inflammatory cytokines such as interleukin-6 (IL-6) cause acute liver injury while serum detectability indicates systemic inflammation.

Aims: We explored a link between systemic IL-6, related acute phase proteins and liver injury in hospitalized COVID-19 patients.

Methods: 655 patients with suspected COVID-19 were screened in the emergency department at the University Hospital of Innsbruck, Austria, between February and April 2020. 96 patients (∼15%) were hospitalized with COVID-19. 15 patients required intensive-care treatment (ICT). Plasma aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transferase, as well as IL-6, C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) were determined by standard clinical assays.

Results: Of all hospitalized COVID-19 patients, 41 (42%) showed elevated aspartate aminotransferase (AST) concentration. COVID-19 patients with elevated AST exhibited significantly higher IL-6 (p < 0.001), ferritin (p < 0.001), LDH (p < 0.001) and CRP (p < 0.05) serum concentrations compared to patients with normal AST. Liver injury correlated with systemic IL-6 (p < 0.001), CRP (p < 0.001), ferritin (p < 0.001) and LDH (p < 0.001) concentration. In COVID-19 patients requiring ICT, correlations were more pronounced.

Conclusion: Systemic inflammation could be a fuel for hepatic injury in COVID-19.

Keywords: Acute phase protein; COVID-19; Cytokines; Interleukin-6; Liver damage; SARS-CoV2.

Fig. 1

IL-6 correlates with AST and is increased in patients with impaired liver function. (A) IL-6 and AST levels correlate in all hospitalized patients. (B) IL-6 levels correlate with AST concentration in non ICU and ICU patients. Displayed are IL-6 concentrations in patients with normal AST and elevated AST in (C) non ICU and (D) ICU patients. Data are shown as mean ± SEM, n: (C-D). *p<0.05; **p<0.01; ***p<0.001 according to Spearman correlation or Student's t-test. AST, aspartate aminotransferase; ICU, intensive care unit; IL-6, interleukin 6.

Fig. 2

CRP correlates with AST and is increased in patients with impaired liver function. (A) CRP and AST levels correlate in all hospitalized patients. (B) CRP levels correlate with AST concentration in non ICU and ICU patients. Displayed are CRP concentrations in patients with normal AST and elevated AST in (C) non ICU and (D) ICU patients. Data are shown as mean ± SEM, n: (C-D). *p<0.05; **p<0.01; ***p<0.001 according to Spearman correlation or Student's t-test. AST, aspartate aminotransferase; CRP, C-reactive protein; ICU, intensive care unit.

Fig. 3

Ferritin correlates with AST and is increased in patients with impaired liver function. (A) Ferritin and AST levels correlate in all hospitalized patients. (B) Ferritin levels correlate with AST concentration in non ICU and ICU patients. Displayed are ferritin concentrations in patients with normal AST and elevated AST in (C) non ICU and (D) ICU patients. Data are shown as mean ± SEM, n: (C-D). *p<0.05; **p<0.01; ***p<0.001 according to Spearman correlation or Student's t-test. AST, aspartate aminotransferase; ICU, intensive care unit.

Fig. 4

LDH correlates with AST and is increased in patients with impaired liver function. (A) LDH and AST levels correlate in all hospitalized patients. (B) LDH levels correlate with AST concentration in non ICU and ICU patients. Displayed are LDH concentrations in patients with normal AST and elevated AST in (C) non ICU and (D) ICU patients. (E) Correlation heat map of biochemical parameters in all hospitalized patients. Tile colours code for magnitude of the correlation with darker shades indicating stronger correlation. The first two decimal digits of r are displayed. Only significant correlations are shown. Data are shown as mean ± SEM, n: (C-D). *p<0.05; **p<0.01; ***p<0.001 according to Spearman correlation or Student's t-test. LDH, lactate dehydrogenase; AST, aspartate aminotransferase; ICU, intensive care unit.