How to manage a patient with elevated liver function tests (LFTs) and influenza (flu)?

Management of Elevated LFTs with Influenza

Monitor liver function tests closely but continue standard influenza management, as mild transaminase elevations are common with influenza itself and typically resolve without specific intervention; however, if LFTs worsen significantly or the patient develops hepatic symptoms, consider oseltamivir as a potential contributor and evaluate for other causes of hepatotoxicity.

Initial Assessment and Monitoring

Determine the degree of LFT elevation and assess for clinical hepatitis:

• Check baseline AST, ALT, total bilirubin, and alkaline phosphatase to quantify the elevation 1
• Monitor for symptoms of hepatic dysfunction including jaundice, right upper quadrant pain, or altered mental status 1
• Assess vital signs including temperature, respiratory rate, pulse, blood pressure, mental status, and oxygen saturation at least twice daily 1
• Rule out other causes of elevated liver enzymes including viral hepatitis, medications/supplements, alcohol use, and liver metastases 1

Common pitfall: Influenza itself can cause mild transaminase elevations without representing true drug-induced hepatotoxicity. Don't automatically attribute LFT abnormalities to oseltamivir if the patient is taking it.

Grading LFT Elevations and Management Strategy

For Grade 1 elevations (AST/ALT >ULN to 3.0× ULN and/or bilirubin >ULN to 1.5× ULN):

• Continue standard influenza management without modification 1
• Monitor LFTs 1-2 times weekly 1
• No specific hepatic intervention required 1

For Grade 2 elevations (AST/ALT 3.0-5.0× ULN and/or bilirubin 1.5-3.0× ULN):

• Temporarily discontinue any hepatotoxic medications if possible 1
• Increase monitoring frequency to every 3 days 1
• If oseltamivir was started, consider whether the benefit of continuing outweighs potential hepatotoxicity risk, though documented cases are rare 2
• Consider hepatology consultation 1

For Grade 3 or higher elevations (AST/ALT >5.0× ULN and/or bilirubin >3.0× ULN):

• Discontinue all potentially hepatotoxic agents 1
• Obtain hepatology consultation 1
• Consider liver biopsy if steroid-refractory or alternative diagnoses would change management 1

Antiviral Therapy Considerations

Oseltamivir and hepatotoxicity:

• Oseltamivir has not been traditionally associated with clinically apparent liver injury despite widespread use 2
• Rare case reports exist linking oseltamivir to acute hepatitis, though causality remains uncertain 2
• The FDA label does not list hepatotoxicity as a recognized adverse effect 3
• Rare instances of reversible liver enzyme elevation have been reported with amantadine, though a specific causal relationship was not established 1

Decision algorithm for antiviral use with elevated LFTs:

• If LFTs are Grade 1 and patient meets criteria (fever >38°C, symptomatic ≤48 hours): Start oseltamivir 75 mg twice daily for 5 days 1, 4
• If LFTs are Grade 2: Weigh risks and benefits; consider starting oseltamivir if within 48 hours of symptom onset and patient is high-risk, but monitor LFTs closely 1
• If LFTs are Grade 3 or higher: Avoid oseltamivir and focus on supportive care 1

Standard Influenza Management Continues

Regardless of LFT elevation, maintain appropriate influenza care:

• Assess for hospital admission criteria: ≥2 unstable factors including temperature >37.8°C, heart rate >100/min, respiratory rate >24/min, systolic BP <90 mmHg, oxygen saturation <90%, inability to maintain oral intake, or abnormal mental status 1, 4
• Provide oxygen therapy if hypoxic, targeting PaO2 >8 kPa and SaO2 ≥92% 1
• Assess for volume depletion and provide IV fluids as needed 1

Antibiotic Considerations

Do not routinely prescribe antibiotics for uncomplicated influenza with elevated LFTs:

• Previously well adults with acute bronchitis complicating influenza do not require antibiotics 1, 5
• Consider antibiotics only if patient develops worsening symptoms suggesting bacterial superinfection (recrudescent fever, increasing dyspnea) 1, 4
• If antibiotics are needed, choose agents with favorable hepatic profiles and avoid hepatotoxic combinations 1

Follow-Up and Discharge Planning

Monitor for resolution of both influenza and LFT abnormalities:

• Recheck LFTs within 3-7 days depending on severity 1
• Ensure clinical stability before discharge using the criteria above 1
• Arrange follow-up for patients with Grade 2 or higher LFT elevations to document normalization 1
• Educate patients on red flag symptoms requiring immediate return: jaundice, severe abdominal pain, confusion, or worsening respiratory status 4