Management of Elevated Liver Function Tests in Patients Taking Hydroxychloroquine
For patients taking hydroxychloroquine (Plaquenil) who develop elevated liver function tests, the recommended approach is to temporarily hold the medication for moderate to severe elevations (ALT >3× ULN) and monitor liver enzymes until normalization before considering resumption at a potentially reduced dose. 1
Assessment of Elevated LFTs
- Classify the severity of liver enzyme elevations using a standardized grading system: mild (1-3× ULN), moderate (>3-5× ULN), severe (>5-20× ULN), or life-threatening (>20× ULN) 2
- Determine the pattern of liver injury by measuring both aminotransferases (ALT, AST) and cholestatic markers (ALP, GGT, bilirubin) 2
- Check for signs of hepatic dysfunction such as increased bilirubin, decreased albumin, or prolonged clotting times 2
- Evaluate for other potential causes of liver enzyme elevation, including viral hepatitis, alcohol use, and other hepatotoxic medications 2
Management Based on Severity of LFT Elevation
Mild Elevation (1-3× ULN)
- Continue hydroxychloroquine with increased monitoring frequency 2
- Monitor liver enzymes weekly until normalization 2
- Evaluate for other potential causes of liver enzyme elevation 2
Moderate Elevation (>3-5× ULN)
- Temporarily hold hydroxychloroquine 1
- Monitor liver enzymes every 2-3 days until stable or improving 2
- Investigate other potential causes of liver injury 2
- Consider resuming hydroxychloroquine at a reduced dose once liver enzymes normalize 1
Severe Elevation (>5-20× ULN)
- Immediately discontinue hydroxychloroquine 1
- Monitor liver enzymes every 1-2 days until stable or improving 2
- Conduct comprehensive evaluation for other causes of liver injury 2
- Consider permanent discontinuation of hydroxychloroquine if no other cause is identified 1
Life-threatening Elevation (>20× ULN)
- Permanently discontinue hydroxychloroquine 1
- Hospitalize for intensive monitoring and supportive care 2
- Urgent hepatology consultation 2
Warning Signs Requiring Immediate Action
- Progressive increase in liver enzymes despite discontinuation of hydroxychloroquine 2
- Development of symptoms such as fatigue, nausea, dark urine, or jaundice 1
- ALT level greater than three times the upper limit of normal with total bilirubin greater than two times the upper limit of normal 1
Monitoring Recommendations
- For patients on hydroxychloroquine without liver abnormalities, the American College of Rheumatology conditionally recommends annual monitoring of CBC and LFTs 3
- For patients with abnormal LFTs, increase monitoring frequency based on severity of elevation 2
- If hydroxychloroquine is restarted after normalization of liver enzymes, monitor LFTs more frequently (every 2-4 weeks) for at least 3 months 2
Special Considerations
- Hydroxychloroquine-induced liver injury is rare but can occur, particularly in patients with porphyria cutanea tarda 1
- Cases of hepatotoxicity typically present with marked elevations in transaminases within days to a month of hydroxychloroquine initiation 1
- Some cases may be associated with other risk factors for hepatic injury (e.g., alcohol use, concomitant hepatotoxic medications) 1
- The risk-benefit ratio should be carefully considered when deciding whether to continue hydroxychloroquine in patients with liver disease 4