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. (Hepatology 2020;72:1169-1176). C oronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in December 2019 in patients with severe pneumonia in Wuhan, China. (1) The World Health Organization declared COVID-19 a global pandemic in March 2020. (2) Although the initial burden of disease was predominantly found in China, (1,3,4,5,6) the United States has reported the most cases of COVID-19 and COVID-19-related death globally since March 26, 2020 and April 11, 2020, respectively. (7) This infection is estimated to have resulted in >11 million cases and 500,000 deaths globally, including 3 million cases and 130,000 deaths in the United States as of July 8, 2020. (7) Whereas patients with COVID-19 typically present with fever and respiratory symptoms consistent

Can elevated concentrations of ALT and AST predict the risk of ‘recurrence’ of COVID-19?

“…in 29 July 2020 reported that abnormal liver tests were commonly observed in hospitalised patients with COVID-19, both at admission (AST 66.9%, ALT 41.6%) and peak hospitalisation (AST 83.4%, ALT 61.6%) [35]. In addition, multivariate analysis revealed an association between abnormal liver tests and severe COVID-19, including ICU admission, mechanical ventilation and death, which suggested that abnormal liver tests may be associated with poorer clinical outcomes, which suggested that abnormal liver tests may be associated with poorer clinical outcomes [35]. These data further demonstrated the predictive value of elevated concentrations of ALT and AST in the progression and prognosis, as well as the ‘recurrence’ of COVID-19.…”

Pathophysiological mechanisms of liver injury in COVID‐19

“…However, in the majority of cases, SARS‐CoV‐2 associated liver injury was generally mild and did not exceed >5 times the upper reference limit, therefore not fulfilling the diagnostic criteria for hypoxic hepaitis 35 . These findings were also obtained in critically ill patients referred to the ICU, suggesting that even in cases of severe respiratory failure during SARS‐CoV‐2 infection, the adequate oxygen supply to the liver is ensured by compensatory mechanisms 35,36,39,149‐154 …”

“…35 These findings were also obtained in critically ill patients referred to the ICU, suggesting that even in cases of severe respiratory failure during SARS-CoV-2 infection, the adequate oxygen supply to the liver is ensured by compensatory mechanisms. 35,36,39,[149][150][151][152][153][154] of DILI associated with tocilizumab use in a COVID-19 patient has been reported. 62 Tocilizumab undergoes minimal hepatic metabolism, and the most probable etiology for its hepatotoxic effect is the interference with the IL-6 pathway, which plays a key role in hepatic regeneration.…”

SARS‐CoV‐2 infection in patients with a normal or abnormal liver

“…According to these data, patients with abnormal AST at admission have a higher risk of mechanical ventilation (OR 3.09, P < 0.001), as are those with abnormal AST, ALT and ALP at peak hospitalization 15 Overall, data support a modest cytopathic acute liver damage by SARS-CoV-2 through a direct cytopathic effect, due to infection of hepatocytes mediated by the highly expressed ACE2 receptors.…”