Hydroxychloroquine and ALT Elevation
Yes, hydroxychloroquine can increase ALT levels in less than 5% of patients, and should be used with caution in patients with pre-existing liver disease, alcohol misuse, or when combined with other hepatotoxic medications. 1
Hepatotoxicity Profile of Hydroxychloroquine
- Hydroxychloroquine is associated with ALT elevation in less than 5% of patients 1
- It is rarely linked to aminotransferase elevations or clinically apparent liver injury 1
- In some cases, hydroxychloroquine can cause significant hepatotoxicity, with reports of up to 10-fold increases in transaminases 2
- Liver enzyme abnormalities are generally self-limiting and typically resolve after discontinuation of the medication 2
Risk Factors for Hydroxychloroquine-Induced Liver Injury
- Pre-existing liver disease increases the risk of hydroxychloroquine-induced hepatotoxicity 1
- Concomitant use with other hepatotoxic medications can increase the risk of liver enzyme elevations 1
- Alcohol misuse is a risk factor for hydroxychloroquine-induced liver injury 1
- Patients with porphyria cutanea tarda (PCT) are at particularly high risk, with cases of marked transaminase elevations (>20 times upper limit of normal) reported within days to a month of hydroxychloroquine initiation 3
Monitoring and Management
- Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, rash, nausea, dark urine, or jaundice 3
- If ALT levels are greater than three times the upper limit of normal or total bilirubin is greater than two times the upper limit of normal, interrupt treatment with hydroxychloroquine and investigate further 3
- Abnormal liver function tests are not an absolute contraindication to hydroxychloroquine use, but regular monitoring is necessary 1
- In patients with COVID-19, liver function abnormalities may be due to multiple factors including the virus itself, its complications, or side effects of therapeutic drugs 1
Special Considerations
- Interestingly, hydroxychloroquine has been observed to potentially protect against liver enzyme abnormalities when used in combination with methotrexate in rheumatoid arthritis patients 4
- Chronic exposure to hydroxychloroquine may alter liver structure and function, with recent animal studies showing Kupffer cell hyperplasia and occasional hepatocyte dysplasia 5
- Desethylchloroquine (a hydroxychloroquine metabolite) levels correlate with renal function, while bidesethylchloroquine levels correlate with liver function tests 6
Conclusion
When prescribing hydroxychloroquine, clinicians should be aware of its potential to cause ALT elevations, particularly in patients with risk factors. Regular monitoring of liver function is recommended, especially in high-risk patients or those on long-term therapy.