Naproxen-induced liver injury.

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

[1]  S. Bresson‐Hadni,et al.  Acute vanishing bile duct syndrome after ibuprofen therapy in a child. , 2004, The Journal of pediatrics.

[2]  J. Carson,et al.  Nonsteroidal Anti-Inflammatory Drug-Induced Hepatic Disorders , 1996, Drug safety.

[3]  S. H. Hussaini,et al.  Idiosyncratic drug-induced liver injury: an overview , 2007, Expert opinion on drug safety.

[4]  R. Victorino,et al.  JAUNDICE ASSOCIATED WITH NAPROXEN , 1980, Postgraduate medical journal.

[5]  L. Laine,et al.  The hepatotoxicity of non‐steroidal anti‐inflammatory drugs , 2004, Alimentary pharmacology & therapeutics.

[6]  G. Falconieri,et al.  Fulminant hepatitis following naproxen administration. , 1986, Human pathology.

[7]  G. Aithal,et al.  Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. , 2007, Clinics in liver disease.

[8]  I. Law,et al.  Jaundice associated with naproxen. , 1976, The New England journal of medicine.

[9]  C. Sempoux,et al.  Bile duct disorders. , 2003, Clinics in liver disease.

[10]  R. Wiesner,et al.  Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis. , 1988, Journal of hepatology.

[11]  L. Ferrell,et al.  Vanishing bile duct syndrome temporally associated with ibuprofen use. , 1996, American Journal of Gastroenterology.

[12]  A. H. Swain,et al.  Cross hepatotoxicity between non-steroidal anti-inflammatory drugs. , 1987, British medical journal.

[13]  C. Degott,et al.  Drug‐induced prolonged cholestasis in adults: A histological semiquantitative study demonstrating progressive ductopenia , 1992, Hepatology.

[14]  R. Denlinger,et al.  The Propionic Acids. Gastrointestinal Toxicity in Various Species , 1988, Toxicologic pathology.