Elevated levels of liver enzymes appear to be a significant risk factor for more severe outcomes in COVID-19 patients. A recent summary from Sara El Quali, MD, Carlos Romero-Marrero, MD, and Miguel Regueiro, MD, examines findings from several recent studies of COVID-19 patients with liver injury in an effort to provide general guidance for treating elevated liver enzymes in this setting. The summary appears in a collection of COVID-19 Curbside Consults from Cleveland Clinic Journal of Medicine.
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services Policy
For most COVID-19 patients, liver injury is more commonly mild and transient, and it is usually hepatocellular. In a retrospective study of 2,273 patients with COVID-19, 45% had mild liver injury, which was defined as levels of alanine aminotransferace (ALT) above the upper limit of normal (ULN) and below two times ULN. In this study, liver injury was severe in just 6.4% of cases. Levels of aspartate aminotransferase (AST) may be a useful indicator of COVID-19 infection, but it is important to note that a cholestatic pattern of injury is rarely associated with COVID-19. Other abnormalities in liver enzymes include elevations in gamma-glutamyl transferase, which occurred in 13.6% of patients with COVID-19.
Assessing elevated liver enzymes and liver injury
When evaluating COVID-19 patients with elevated liver enzymes, it is important to consider other etiologies, such as hepatitis A, B and C. Ischemia, cardiac and muscle injury, and cytokine release syndrome can also be associated with COVID 19 and transaminase elevations. Other hepatic manifestations of COVID-19 have been reported, including acute portal vein thrombosis in a patient with abdominal pain, fever, jaundice and elevated levels of transaminases. Drug-induced liver injury has been seen in up to 25.4% of patients with COVID-19. Remdesivir, an antiviral drug that may shorten the time it takes to recover from COVID-19, is associated with increased liver enzymes in about 15.2% of patients. While abnormal liver biochemistries are not a contraindication to COVID-19 therapies, liver enzymes should be carefully monitored in all hospitalized COVID-19 patients.
In patients with severe COVID-19, liver injury appears to be common and is associated with negative outcomes. In a retrospective study of 1,059 COVID-19 patients, liver injury at presentation was an independent predictor of death or intensive care unit (ICU) admissions. In patients with severe hypoxia, liver injury was the second most accurate predictor of poor outcomes in this study. Another study notes that severe liver injury was associated with elevated levels of inflammatory markers and higher rates of intubation, ICU admission and mortality. Patterns of liver enzymes have also been associated with a negative prognosis. Hypoalbuminemia on admission to the hospital appears to be a marker of severe disease. In a large cohort study, peak ALT was associated with severe disease, while an elevated baseline AST level was associated with ICU admission, intubation and death in another study.
Liver transplant and liver disease
Although earlier studies indicated that liver transplant recipients did not show worse COVID-19 outcomes, newer studies have tempered those findings. Recent U.S. data have shown a mortality rate of 29% among hospitalized COVID-19 patients with liver transplant. COVID-19 patients with preexisting liver disease have been found to be at increased risk for mortality compared to COVID-19 patients without liver disease. This was especially true for cirrhosis patients, according to a study of 202 COVID-19 patients.
A list of recommendations for outpatient management of patients with decompensated cirrhosis, those undergoing liver transplant evaluation and those currently on a transplant waitlist during the COVID-19 pandemic is available in the full Curbside Consult article, available here.