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High Liver Enzyme Levels Are Associated With Severe COVID-19 Cases

While pneumonia, acute respiratory distress syndrome (ARDS) and multiorgan failure are the typical causes of severe illness and death in patients with COVID-19, non-pulmonary manifestations also are a problem. A Yale study reveals that high levels of liver enzymes are associated with poor outcomes when patients are infected with the novel coronavirus. Here is more information.

NEW HAVEN, CT – High levels of liver enzymes are associated with poor outcomes for COVID-19 patients, including intensive care unit admission, mechanical ventilation and death, according to a new study.

A rapid communication in the journal Hepatology reports that patients with novel coronavirus infection presented with abnormal liver tests at much higher rates than suggested by earlier studies. The study team also raises questions on how medications affected those levels.

Noting that previous Chinese studies found that about 15% of patients with COVID-19 had abnormal liver tests, researchers from the Yale Liver Center examined retrospectively 1,827 COVID-19 patients who were hospitalized in the Yale New Haven Health system between March and April. They determined much higher incidence of abnormal liver tests, advising that between 41.6% and 83.4% of patients, depending on the specific test, fell into that category.

The Yale researchers reviewed results of five liver tests, looking at factors such as elevations in aspartate aminotransferase (AST) and alanine transaminase (ALT), which indicate liver cell inflammation; an increase in bilirubin, which indicates liver dysfunction; and increased levels of alkaline phosphatase (ALP), which may indicate inflammation of bile ducts.

"We can speculate that U.S. patients may have an increased rate of other risk factors such as alcoholic or non-alcoholic fatty liver disease," said senior author Joseph Lim, MD, of Yale.

 Co-author Michael Nathanson, MD, PhD, of Yale pointed out, "In the U.S., close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C."

“The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, is associated with significant morbidity and mortality due to pneumonia, acute respiratory distress syndrome (ARDS) and multiorgan failure,” the authors write. “Liver injury has been reported as a non‐pulmonary manifestation of COVID‐19 but characterization of liver test abnormalities and their association with clinical outcomes is incomplete.”

The study notes that Abnormal liver tests were commonly observed in hospitalized patients with COVID‐19, both at admission (AST 66.9%, ALT 41.6%, ALP 13.5%, TBIL 4.3%) and peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, TBIL 16.1%). While Most patients with abnormal liver tests at admission had minimal elevations 1‐2x ULN (AST 63.7%, ALT 63.5%, ALP 80.0%, TBIL 75.7%), researchers write, many  of those patients had abnormal liver tests pre‐hospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, TBIL 44.4%).

Based on multivariate analysis, the authors conclude that an association exists between abnormal liver tests and severe COVID‐19, including ICU admission, mechanical ventilation, and death. In addition, they observed links with age, male gender, BMI, and diabetes mellitus.

The study also notes that treatment could play a role, explaining, “Medications used in COVID‐19 treatment (lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab) were associated with peak hospitalization liver transaminase elevations >5x ULN.

"We observed a strong association between the use of COVID-19 medications and abnormal liver tests," Lim said, but added that it wasn’t possible to determine if the abnormal tests were due to "drug-induced liver injury" as opposed to the disease.