Liver enzyme elevations in COVID-19 secondary to other conditions

The elevations in liver enzymes that occur in patients with COVID-19 may be due to other conditions and not as a direct result of COVID-19, according to a poster presented at the AASLD 2020 Liver Meeting.

Researchers from the Yale University School of Medicine, New Haven, Connecticut, US, looked at 834 patients (median age 68 years, 47.6 percent male, 40.2 percent obese) who had been hospitalized for COVID-19 in April 2020. Severity of COVID-19 was defined as use of vasopressors and intubation, ischaemia as use of vasopressors, hyperinflammatory state as C-reactive protein >100 mg/dL or ferritin >1,000 ng/mL, and hypercoagulability as venous thromboembolism, D-dimer >5 mg/dL, or fibrinogen >700 mg/dL during hospitalization.

Patients were followed up for a median 10 days. Severe COVID-19 occurred in 138 patients. A total of 521 patients had abnormal aspartate aminotransferase (AST) levels at admission.

AST and alanine aminotransferase (ALT) levels at admission were significantly higher in patients with severe vs non-severe COVID-19 (median 52 vs 37 U/L [AST] and 35 vs 24 U/L [ALT]; p<0.001 for both). [AASLD 2020, abstract LP27]

Peak AST and ALT levels were also significantly higher among patients with severe vs non-severe COVID-19 (median 116.5 vs 54.5 U/L [AST] and 97 vs 39 U/L [ALT]; p<0.001 for both). AST levels peaked a median 3 days post-hospitalization.

Patients with severe COVID-19 also had lower albumin levels than those with non-severe COVID-19 (median 3.3 vs 3.6 g/dL; p<0.001). However, bilirubin levels did not differ between the groups (median 0.56 vs 0.49 mg/dL; p=0.14) nor did international normalized ratio (INR; median 1.12 vs 1.05; p=0.18).

During hospitalization, AST >5 times the upper limit of normal (ULN) occurred in 105 patients. Independent predictors of AST >5X ULN were ischaemia (odds ratio [OR], 3.9, 95 percent confidence interval [CI], 2.4–6.3) and use of tocilizumab (OR, 3.5, 95 percent CI, 1.9–6.6), though not hyperinflammation or hypercoagulability (ORs, 1.3 and 1.8, respectively).

A total of 138 patients (16.5 percent) died during hospitalization. Ischaemia was an independent predictor of mortality (OR, 3.4, 95 percent CI, 2.2–5.4), though AST >5X ULN was not (OR, 1.4, 95 percent CI, 0.8–2.5).

Over the hospitalization period, there was significant correlation between changes in log AST and log ALT (r=0.89), but no correlation between changes in log AST and log INR (r=0.10).

Abnormalities with liver enzymes, primarily increases in AST, ALT, and bilirubin levels, are commonly observed in patients with COVID-19, said the researchers. However, whether these abnormalities are the result of liver injury due to SARS-CoV-2 infection or secondary to other conditions (eg, ischaemia, hypercoagulability) remains unknown, as is their potential association with liver failure or death.

“In patients with COVID-19, AST abnormalities are indicative of liver injury but are generally mild and transient. AST abnormalities are not associated with liver insufficiency and are not an independent predictor of death,” they said. 

“Hepatocellular injury associated with COVID-19 is secondary to other insults, mainly ischaemia or drug-induced liver injury,” they concluded.