In-hospital mortality risk and/or need for mechanical ventilation are higher in the presence of abnormal liver enzyme levels in Covid-19 patients with no past history of liver disease. Patients with cholestatic liver injury are at the highest risk for adverse outcomes, according to a new study published in the World Journal of Gastroenterology.

The multicenter study reviewed medical records of 10,614 patients with no prior chronic liver disease and who were hospitalized with lab-confirmed Covid-19 between March 2020 and April 2020. Patients with known chronic liver disease, those younger than 18 years and who did not have baseline (within 24 hours of presentation) serum alanine aminotransferase (ALT). The patients stayed in the hospital for an average duration of 6 days. Their media age was 65 years and nearly 60% of the study population was male. Hypertension was the most prevalent comorbid condition (58%) followed by obesity (39%) and diabetes (36%).

Based on the values obtained, serum AST, ALT, ALP and total bilirubin levels were categorized into four groups: patients with levels within normal limits, patients with levels greater than the upper limit of normal (ULN) to ≤4 times ULN, patients with >4 times ULN to ≤10 times ULN and those with levels > 10 times the ULN.

The ULN for AST was 40 U/L and for ALT was 25 U/L for women and 35 U/L for men; for ALP it was 125 U/L and for total bilirubin the ULN was 1.2 mg/dL.

Serum AST levels were raised in 59% patients and ALT in 54%. Patients in the second group showed the most elevation in liver enzymes. AST > ALT was seen in 76% patients at the time of presentation. Nearly 9% patients showed hepatocellular pattern (ALT > 3 × ULN, ALP ≤ 2 × ULN) of abnormal liver biochemistry; 1.3% had cholestatic pattern (ALP > 2 × ULN, ALT ≤ 3 × ULN), while a mixed pattern (ALT > 3 × ULN, ALP > 2 × ULN) was seen in almost 1% of patients. But bilirubin was raised in only 5% of patients and just 13% showed high ALP levels.

A gender difference was also observed. More men than women showed high AST (64.8% vs 50.1%, respectively) and bilirubin (5.9% vs 2.8%, respectively). However, women had high ALP levels compared to men; 14.2% vs 12.0%, respectively. No gender difference was noted with regard to ALT.

The risk of in-hospital mortality and the composite outcome of in-hospital mortality or need for mechanical ventilation was higher in patients with high AST levels (unadjusted HR 1.34; adjusted HR 1.67) and (unadjusted HR 1.34; adjusted HR 1.77) respectively. A similar association was observed for raised ALT (adjusted HR 1.21; adjusted HR 1.21) and ALP (adjusted HR 1.29; adjusted HR 1.39).

The mortality increased 3-folds in patients with AST > 10 times the ULN (adjusted HR 2.64); the likelihood of the need for mechanical ventilation also increased three times in this group. “Increasing severity of AST abnormalities was associated with incrementally poor survival and need for mechanical ventilation (adjusted HR 3.38).”

A correlation between mortality and the pattern of liver injury was also observed. The risk of in-patient mortality (adjusted HR 1.72) and the composite outcome of in-patient mortality or need for mechanical ventilation (adjusted HR: 1.84) was higher in patients with baseline AST>ALT. Patients with severe cholestatic liver injury were at higher risk of in-patient mortality (adjusted HR 1.57) and the composite outcome of in-patient mortality or need for mechanical ventilation (adjusted HR: 2.05).

This study has shown that abnormal liver enzymes were prevalent in more than half of hospitalized Covid-19 patients at the time of presentation and before starting treatment for the infection. It also demonstrates an association of raised baseline ALT, AST and ALP with higher odds of occurrence of adverse outcomes in terms of mortality or the requirement of mechanical ventilation in hospitalized Covid-19 patients. Despite being not very prevalent compared to the hepatocellular pattern, a cholestatic pattern of liver enzymes at baseline, showed a higher association with adverse prognosis. Such patients should be carefully monitored. Liver function tests should therefore be a part of the initial evaluation of Covid-19 patients being managed as outpatients or as inpatients.

Reference

1. Bernstein D, et al. Presentation, patterns and predictive value of baseline liver tests on outcomes in COVID-19 patients without chronic liver disease. World J Gastroenterol. 2021 Nov 14;27(42):7350-7361. doi: 10.3748/wjg.v27.i42.7350.