Abnormal Liver Tests in COVID‐19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network

Abstract

Background and Aims The coronavirus‐19 disease (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 virus, is associated with significant morbidity and mortality attributable to pneumonia, acute respiratory distress syndrome, and multiorgan failure. Liver injury has been reported as a nonpulmonary manifestation of COVID‐19, but characterization of liver test abnormalities and their association with clinical outcomes is incomplete. Approach and Results We conducted a retrospective cohort study of 1,827 patients with confirmed COVID‐19 who were hospitalized within the Yale‐New Haven Health System between March 14, 2020 and April 23, 2020. Clinical characteristics, liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], total bilirubin [TBIL], and albumin) at three time points (preinfection baseline, admission, and peak hospitalization), and hospitalization outcomes (severe COVID‐19, intensive care unit [ICU] admission, mechanical ventilation, and death) were analyzed. Abnormal liver tests were commonly observed in hospitalized patients with COVID‐19, both at admission (AST 66.9%, ALT 41.6%, ALP 13.5%, and TBIL 4.3%) and peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, and TBIL 16.1%). Most patients with abnormal liver tests at admission had minimal elevations 1‐2× the upper limit of normal (ULN; AST 63.7%, ALT 63.5%, ALP 80.0%, and TBIL 75.7%). A significant proportion of these patients had abnormal liver tests prehospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, and TBIL 44.4%). Multivariate analysis revealed an association between abnormal liver tests and severe COVID‐19, including ICU admission, mechanical ventilation, and death; associations with age, male sex, body mass index, and diabetes mellitus were also observed. Medications used in COVID‐19 treatment (lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab) were associated with peak hospitalization liver transaminase elevations >5× ULN. Conclusions Abnormal liver tests occur in most hospitalized patients with COVID‐19 and may be associated with poorer clinical outcomes.