Why do US COVID patients have more abnormal liver tests?

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In a new study, patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier research.

The researchers also discovered that higher levels of liver enzymes—proteins released when the liver is damaged—were associated with poorer outcomes for these patients, including ICU admission, mechanical ventilation, and death.

Previous studies in China found that approximately 15% of patients with COVID-19 had abnormal liver tests.

The new study looked retrospectively at 1,827 COVID-19 patients who were hospitalized in the Yale New Haven Health system between March and April. The researchers found that the incidence of abnormal liver tests was much higher—between 41.6% and 83.4% of patients, depending on the specific test.

In all, the researchers examined 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.

Although the researchers do not know why the incidence of abnormal liver tests was so much higher than in previous studies from China, senior author Joseph Lim, professor of medicine and director of the Yale University Viral Hepatitis Program, says other health differences between the Chinese and US populations could account for it.

“We can speculate that US patients may have an increased rate of other risk factors such as alcoholic or non-alcoholic fatty liver disease,” he says.

Liver disease is widespread in the US population. “In the US, close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C,” says coauthor Michael Nathanson, professor of medicine (digestive diseases), professor of cell biology, and director of the Yale Liver Center.

Because the researchers had access to patients’ health records, they were also able to look at their liver tests prior to being diagnosed with COVID-19. Approximately one-quarter of patients in the study had abnormal liver tests prior to being admitted for the virus. But regardless of whether patients came to the hospital with existing liver problems or developed them during their COVID-19-related hospitalization, the researchers observed a strong association between abnormal liver tests and the severity of the COVID-19 cases, they say.

Rather than the liver itself driving poorer outcomes in COVID-19 patients, the organ is more likely “a bystander” affected by the hyperinflammation associated with COVID-19 and by the side effects of related treatments, Nathanson says.

The study notes a relationship between drugs used to treat severe COVID-19 and liver damage, most significantly the drug tocilizumab.

“We observed a strong association between the use of COVID-19 medications and abnormal liver tests,” says Lim, but adds that they could not confidently tease out that the abnormal tests were due to “drug-induced liver injury” as opposed to the disease.

The researchers have additional clinical and lab-based studies underway to further understand COVID-19’s effect on liver pathology.

The study appears in Hepatology.

Source: Yale University