Are liver function tests (LFTs) required before starting Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

Liver Function Tests Before Starting Paxlovid

Liver function tests are not required before initiating Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment in patients without known liver disease. However, baseline LFTs should be obtained in hospitalized patients and those with pre-existing liver conditions, with regular monitoring during treatment regardless of baseline results.

Clinical Approach to LFT Monitoring with Paxlovid

Pre-Treatment Assessment

For outpatient COVID-19 patients without known liver disease:

• Baseline LFTs are not mandatory before starting Paxlovid 1
• Abnormal liver function is not a contraindication to COVID-19 treatment 1
• The urgency of early antiviral treatment (within 5 days of symptom onset) typically outweighs the need for pre-treatment laboratory work

For hospitalized patients or those with risk factors:

• Obtain baseline LFTs as part of standard COVID-19 assessment 1
• Screen for hepatitis B surface antigen if corticosteroids or immunosuppressants will be used for ≥7 days 1
• Check for pre-existing chronic liver disease, as these patients have higher risk of severe COVID-19 outcomes 2, 3

During Treatment Monitoring

Frequency of monitoring:

• Monitor LFTs twice weekly in patients on potentially hepatotoxic medications 1
• Increase monitoring frequency if abnormal liver function develops 1
• More frequent monitoring is warranted in patients with pre-existing liver disease 1

Important consideration: Ritonavir (the boosting component of Paxlovid) has known hepatotoxic potential, similar to lopinavir-ritonavir which was associated with increased ALT levels in COVID-19 patients 2, 4

Management of Abnormal LFTs During Treatment

Mild elevations (ALT/AST <5× upper limit of normal):

• Continue Paxlovid with close monitoring 1
• Investigate alternative causes including COVID-19 itself, which causes liver dysfunction in 14-53% of cases 5, 6, 3
• Consider drug-drug interactions with other medications 1

Moderate-to-severe elevations (≥5× upper limit of normal):

• Evaluate for other causes: direct viral cytopathic effect, cytokine storm, hypoxia, sepsis, or drug-induced liver injury 1, 6
• Consider discontinuation if ALT/AST >5× ULN with symptoms or jaundice 7
• Investigate for hepatitis B or C reactivation with serological testing 1

Special Populations Requiring Heightened Vigilance

Patients with chronic liver disease:

• Have higher risk of severe COVID-19 and mortality 2, 3
• Require baseline and serial LFT monitoring 1
• The severity of COVID-19 infection, not the liver disease itself, is the primary predictor of death 2

Patients with hepatitis B:

• Screen for HBsAg before initiating immunosuppressive COVID-19 therapies 1
• Initiate or continue antiviral therapy to prevent reactivation 1
• Do not stop nucleoside antiviral therapy during COVID-19 treatment 1

Key Clinical Pitfalls to Avoid

• Do not delay Paxlovid initiation in outpatients waiting for LFT results, as the 5-day treatment window is critical for efficacy 1
• Do not attribute all LFT abnormalities to medication - COVID-19 itself causes hepatic dysfunction in nearly half of patients, particularly those with severe disease 5, 6, 3
• Do not assume LFT deterioration represents drug toxicity alone - consider COVID-19 complications such as myositis (AST > ALT), ischemia, cytokine release syndrome, or sepsis 1
• Do not withhold treatment based solely on abnormal baseline LFTs unless there is moderate-to-severe liver injury 1

Evidence Context

The available guidelines address older COVID-19 therapies (lopinavir-ritonavir, remdesivir) rather than Paxlovid specifically 1. However, since Paxlovid contains ritonavir as a boosting agent, the same hepatotoxicity monitoring principles apply 2, 4. The consensus across multiple international guidelines is that abnormal liver function should not prevent COVID-19 treatment initiation, but warrants systematic monitoring 1.