Monitoring Liver Function Tests in Patients Taking Plaquenil (Hydroxychloroquine)
The American College of Rheumatology conditionally recommends annual monitoring of CBC and LFTs for patients on hydroxychloroquine without pre-existing liver abnormalities. 1
Baseline and Routine Monitoring
Obtain baseline liver function tests before initiating hydroxychloroquine therapy, including ALT, AST, alkaline phosphatase, and bilirubin to establish a reference point. 1
For patients without liver disease, perform annual monitoring of LFTs along with complete blood count as part of routine surveillance. 1
Hydroxychloroquine-induced hepatotoxicity is rare, making routine frequent monitoring unnecessary in asymptomatic patients with normal baseline liver function. 2
When LFTs Become Elevated
If liver enzymes become elevated during hydroxychloroquine therapy, classify the severity and adjust management accordingly:
Mild Elevation (1-3× Upper Limit of Normal)
- Continue hydroxychloroquine with increased monitoring frequency (every 2-4 weeks until stable). 1
- Investigate alternative causes including viral hepatitis, alcohol use, other medications, and underlying liver disease. 1
Moderate Elevation (>3-5× ULN)
- Monitor liver enzymes every 2-3 days until stable or improving. 1
- Consider temporarily holding hydroxychloroquine while investigating other causes. 1
- Assess for signs of hepatic dysfunction including bilirubin, albumin, and coagulation studies. 1
Severe Elevation (>5-20× ULN)
- Monitor liver enzymes every 1-2 days until stable or improving. 1
- Discontinue hydroxychloroquine immediately. 1
- Evaluate for acute liver injury from all potential sources. 3
Life-Threatening Elevation (>20× ULN)
- Hospitalize for intensive monitoring and supportive care. 1
- Discontinue all potentially hepatotoxic medications. 3
Pattern Recognition
Measure both aminotransferases (ALT, AST) and cholestatic markers (ALP, GGT, bilirubin) to determine the pattern of liver injury, which helps identify the underlying cause. 1
Hydroxychloroquine can cause either hepatocellular or cholestatic patterns of injury, though this is uncommon. 2
Restarting Therapy
- If hydroxychloroquine is restarted after normalization of liver enzymes, monitor LFTs more frequently (every 2-4 weeks) for at least 3 months to detect early recurrence of hepatotoxicity. 1
Special Populations
Patients with pre-existing liver disease require more intensive monitoring:
For patients with known chronic liver disease, monitor liver function every 1-3 months rather than annually. 4
Screen for alcohol use and chronic viral hepatitis before initiating therapy in patients with baseline liver abnormalities. 4
In patients with decompensated cirrhosis, hydroxychloroquine should be used with extreme caution as drug metabolism may be significantly impaired. 2
Common Pitfalls
Do not assume elevated LFTs are automatically due to hydroxychloroquine - idiosyncratic drug reactions are equally common in patients with normal or abnormal baseline liver function. 2
Avoid checking only a single liver enzyme - a complete panel is necessary to characterize the pattern and severity of injury. 3
Many clinicians over-monitor asymptomatic patients or under-respond to significant elevations - use the severity-based algorithm above to guide appropriate action. 5