Hydroxychloroquine Does Not Typically Cause Fatty Liver
Hydroxychloroquine (Plaquenil) is not recognized as a cause of hepatic steatosis (fatty liver) and is not included among the established steatogenic medications that clinicians should avoid or discontinue in patients with fatty liver disease. 1, 2
Evidence from Guidelines on Steatogenic Medications
The most authoritative guidance on medications that cause fatty liver comes from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, which specifically identify the following drugs as steatogenic agents requiring avoidance or discontinuation: amiodarone, tamoxifen, methotrexate, valproate, glucocorticoids, and certain antiretrovirals. 1, 2 Notably, hydroxychloroquine is absent from this list despite comprehensive reviews of drug-induced steatosis. 3, 4
Hydroxychloroquine's Actual Hepatic Risk Profile
The National Institute of Health LiverTox resource rates hydroxychloroquine with a likelihood score of D, meaning it is a "possible rare cause of clinically apparent liver injury" - but this refers to hepatocellular injury patterns (aminotransferase elevations, hypersensitivity reactions), not steatosis. 5
Documented hepatic effects include:
- Rare aminotransferase elevations without steatosis 5
- Hypersensitivity reactions in patients with acute intermittent porphyria or porphyria cutanea tarda, presenting with fever and transaminase elevations 5
- Fulminant hepatic failure in extremely rare cases (only 2 case reports from 1994) 6
- Hepatic concentration of the drug, requiring caution in patients with pre-existing hepatic disease 5
Important Distinction: Steatosis as Risk Factor vs. Causative Agent
Recent research demonstrates that pre-existing hepatic steatosis may alter hydroxychloroquine metabolism and potentially increase its toxicity, rather than hydroxychloroquine causing steatosis. 7 In HepaRG cell models with induced steatosis, hydroxychloroquine showed:
- Modified metabolic signature with detection of a new metabolite (carboxychloroquine) 7
- Higher cytotoxicity in cells with fatty acid accumulation 7
- Further enhancement of pre-existing neutral lipid accumulation 7
This means patients with fatty liver may be at higher risk for hydroxychloroquine toxicity, but the drug itself is not initiating the steatosis. 7
Clinical Monitoring Recommendations
While hydroxychloroquine does not cause fatty liver, the American Gastroenterological Association recommends monitoring liver function tests in patients taking hydroxychloroquine who have pre-existing hepatic disease or are taking other hepatotoxic drugs. 5 This is due to:
- The drug's hepatic concentration 5
- Potential for rare hepatocellular injury 5
- Altered drug metabolism in patients with steatosis 7
Common Pitfall to Avoid
Do not confuse hydroxychloroquine with chloroquine - while both are antimalarial medications with similar names and similar (non-steatotic) hepatic risk profiles, they are distinct agents with no known cross-reactivity in liver injury patterns. 5