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Elevations in Aminotransferases Mirror Severity of COVID-19

Key findings

  • This is the first published report in which liver biochemistries in COVID-19 patients were followed over the course of hospitalization at a U.S. center
  • The pattern of liver biochemistries was generally consistent with liver injury, with aspartate aminotransferase most predominantly elevated
  • There was no signal of increased liver injury in patients on statin therapy, including those newly started on statins
  • The degree of liver injury was associated with length of stay, ICU admission and intubation, but not death

Nearly half of patients with COVID-19 exhibit elevated liver biochemistries on hospital admission, most frequently in aspartate aminotransferase (AST) or alanine aminotransferase (ALT). The cause is unclear, and there is little data on the trend during hospitalization and the association between liver biochemistries and COVID-19 outcomes.

Gastroenterologist Esperance Schaefer, MD, MPH, of the Division of Gastroenterology at Massachusetts General Hospital, Raymond Chung, MD, vice chief of the Division of Gastroenterology and director of the Liver Center, Patricia P. Bloom, MD, former fellow, and colleagues followed liver biochemistries in the first cohort of patients admitted to Mass General with moderate to severe COVID-19. In Hepatology, they report that the pattern of liver biochemistries was generally consistent with liver injury, with an AST predominance, and worsened with length and severity of COVID-19, but the extent of liver test elevations was not associated with the risk of death.

Study Details

The researchers studied 60 patients with COVID-19 who were admitted between March 21 and March 28, 2020, and were followed through April 3, 2020. In accordance with institutional guidance, patients with COVID-19 were continued on a statin if already prescribed; if not, physicians were asked to consider starting atorvastatin 40 mg daily unless there was a contraindication.

The first 50 patients were included in the cohort consecutively. The subsequent 10 were included consecutively but only if they had not been placed on statin therapy within the first 48 hours of admission.

Trends in Liver Biochemistries

Of the patients studied, 41 (69%) had at least one abnormal liver biochemistry on admission. Median AST was higher than ALT at admission (46 vs. 30 U/L) and remained higher for most of the hospitalization. Aminotransferases rose above the upper limit of normal in 54 patients (93%).

AST was highly correlated with ALT on admission (r = 0.91; P < .0001) and on every subsequent day of admission. In addition, peak AST correlated with peak ALT during hospitalization (r = 0.97; P < .0001). This suggests true hepatic injury as the predominant source of aminotransferase elevation.

Ten patients (17%) developed grade 3 or 4 hepatocellular injury. In eight of those patients, AST or ALT began to rise within the first four days of admission.

Liver Biochemistries and Statin Use

In total, 48 patients (80%) received a statin during their hospitalization; among them, 24 had a previous prescription and 24 did not. There was no significant difference in the grade of hepatocellular injury between patients who did or did not use a statin during hospitalization.

Liver Biochemistries and COVID-19 Outcomes

At the end of the study period, 28 patients had been discharged, six had died and 26 were still admitted, of whom 22 had required ICU admission and 19 required intubation. The median length of stay was nine days overall (range, 1–20 days) and 12 days in the subgroup still admitted (range, 6–20 days).

At the time of analysis:

  • Admission AST was higher in patients requiring intubation (69 vs. 49 U/L; P < .05) but was not a significant predictor of ICU admission, intubation or death
  • Grade of hepatocellular injury was associated with length of stay, ICU admission and intubation, but not death

Monitoring Recommended

Given the high incidence of abnormal liver biochemistries in this cohort, liver biochemistries should be monitored in all hospitalized patients with COVID-19, as the American Association for the Study of Liver Diseases now recommends.

Why Statins?

Statins are a component of COVID-19 therapy at Mass General because:

  • COVID-19 has cardiovascular complications that statin therapy might protect against
  • Statins may enhance the innate immune response to SARS-CoV-2
  • The use of statins has shown to be safe in acute respiratory distress syndrome and may be associated with less severe viral pneumonia

Randomized, controlled trials are examining the safety and efficacy of statin therapy in COVID-19.

69%
of patients hospitalized with COVID-19 had at least one abnormal liver biochemistry result at admission

93%
of patients hospitalized with COVID-19 developed aminotransferases above the upper limit of normal

17%
of patients hospitalized with COVID-19 developed grade 3 or 4 liver injury

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Refer a patient to the Division of Gastroenterology

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