Sources and clinical significance of aspartate aminotransferase increases in COVID-19

Abstract

Background: Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk.

Methods: 2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and γ-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays.

Results: AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5-69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3-45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes.

Conclusion: The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear.

Keywords: Aspartate aminotransferase; COVID-19; Liver injury; SARS-CoV-2.

Fig. 1

Box and whisker plots showing the distribution of results of evaluated parameters in studied COVID-19 patients, according to the survival outcome. The dashed lines indicate the upper reference limits of each test. Note that, except for CRP, the scale of the y-axis is logarithmic. AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; CRP, C-reactive protein.

Fig. 2

Box and whisker plots showing the distribution of results of evaluated parameters in studied COVID-19 patients, according to the hospitalization in intensive care unit vs. hospitalization in nonintensive wards. The dashed lines indicate the upper reference limits of each test. Note that, except for CRP, the scale of the y-axis is logarithmic. ICU, intensive care unit; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; CRP, C-reactive protein.

Fig. 3

Relationships of aspartate aminotransferase (AST) values at peak with alanine aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) obtained on the same day in studied COVID-19 patients. (A) All patients; (B) 20 patients with AST > 500 U/L removed. In part A), coefficients of determination (R²) are reported.