Intrahepatic cholestasis induced by phenylbutazone

Area of Science:

• Hepatology
• Clinical Pharmacology
• Immunology

Background:

• Intrahepatic cholestasis is a liver condition where bile flow is impaired.
• Drug-induced liver injury (DILI) is a significant cause of liver disease.
• Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) historically used for inflammatory conditions.

Observation:

• A patient presented with intrahepatic cholestasis after 1 month of phenylbutazone use for knee pain.
• Liver biopsy showed pericentral cholestasis and inflammatory cell infiltration, indicative of a drug reaction.
• Following drug cessation, clinical and biochemical liver parameters normalized within 2 months.

Findings:

• A subsequent provocation test with phenylbutazone re-induced liver enzyme elevations, confirming causality.
• Serum transaminases normalized rapidly, while alkaline phosphatase remained elevated for a month.
• The pattern suggests a hypersensitivity-mediated cholestatic reaction to phenylbutazone.

Implications:

• Phenylbutazone should be considered a potential cause of drug-induced cholestatic jaundice.
• Hypersensitivity reactions are a key mechanism in certain NSAID-induced liver injuries.
• Careful monitoring and provocation testing can aid in diagnosing drug-induced liver disease.