How often should I check liver function tests (LFTs) in a patient on remdesivir (GS-5734) for COVID-19?

Liver Function Test Monitoring for Remdesivir in COVID-19

Monitor liver function tests twice weekly in patients receiving remdesivir for COVID-19, with more frequent monitoring if abnormalities develop. 1

Baseline Assessment

• Obtain baseline LFTs before initiating remdesivir in hospitalized patients as part of standard COVID-19 assessment, though the urgency of treatment in outpatients may not require waiting for results. 1
• Screen for hepatitis B surface antigen (HBsAg) if corticosteroids or immunosuppressants will be used for ≥7 days, as these medications increase reactivation risk. 1

Monitoring Frequency During Treatment

• The optimal monitoring interval is twice weekly for patients on potentially hepatotoxic medications like remdesivir, particularly those with pre-existing liver disease. 1
• Increase monitoring frequency to more than twice weekly if any LFT abnormalities emerge during treatment. 1
• This recommendation is based on the known hepatotoxicity profile of remdesivir, which causes mild ALT elevation to >2 times upper limit of normal (ULN) and mild-to-moderate AST elevation to >3-4 times ULN. 1

Clinical Context and Rationale

Remdesivir carries documented hepatotoxic potential that necessitates vigilant monitoring:

• Clinical trials showed 25% of patients developed increased alanine transaminase and 35% had elevated aspartate transaminase levels during remdesivir treatment. 2
• Elevated hepatic enzymes were the most frequent adverse drug reaction in compassionate-use cohorts. 3
• Some trials reported premature discontinuation due to aminotransferase or bilirubin increases (3% vs 0% in placebo). 3
• Rare cases of acute liver failure secondary to remdesivir have been documented. 4

Management Based on LFT Results

For mild elevations (ALT/AST <5× ULN):

• Continue remdesivir with close monitoring. 5
• Investigate alternative causes including COVID-19 itself, which causes liver derangement in 14.8-53% of patients. 6
• Review all concomitant medications for drug-drug interactions and additional hepatotoxic effects. 5

For moderate-to-severe elevations (ALT >5× ULN or ALP >2× ULN, and total bilirubin >2× ULN):

• Strongly consider discontinuing remdesivir, as off-label treatments with uncertain benefits should be stopped in the setting of moderate-to-severe liver injury. 1
• Evaluate for other causes including viral hepatitis reactivation, drug-induced liver injury, and COVID-19-related hepatic dysfunction. 5
• Perform serological testing for hepatitis B and C if not already done. 5

Special Populations Requiring Enhanced Monitoring

• Patients with pre-existing chronic liver disease require baseline and serial LFT monitoring due to higher risk of severe outcomes. 5
• Patients with chronic hepatitis B need antiviral therapy initiated or continued to prevent reactivation, especially if receiving immunosuppressive COVID-19 therapies. 1, 5
• Patients on multiple potentially hepatotoxic medications warrant the twice-weekly monitoring schedule at minimum. 1

Critical Pitfalls to Avoid

• Do not delay remdesivir initiation in outpatients waiting for baseline LFT results, as this reduces treatment efficacy and the urgency of early antiviral therapy outweighs pre-treatment laboratory work. 5
• Do not attribute all LFT abnormalities solely to remdesivir—COVID-19 itself commonly causes liver derangement, and other concurrent medications or underlying liver diseases may be responsible. 5, 6
• Do not withhold treatment based solely on abnormal baseline LFTs unless there is moderate-to-severe liver injury (as defined above). 5
• Avoid sending COVID-19 patients to radiology for liver imaging unless there are clinical symptoms of biliary pathology; use bedside ultrasonography for infection control. 1
• Exercise caution by avoiding concomitant potentially hepatotoxic drugs when possible during remdesivir treatment. 7