Nefazodone-Induced Liver Failure: Report of Three Cases

16 February 1999 | Volume 130 Issue 4 Part 1 | Pages 285-288

Background: Liver failure is a rare but devastating result of drug toxicity.

Objective: To describe three cases of subfulminant liver failure that were probably caused by nefazodone, a new antidepressant that is a synthetically derived phenylpiperazine.

Design: Case series.

Setting: Two university medical centers and a children's hospital.

Patients: Three women 16 to 57 years of age.

Intervention: Two patients underwent liver transplantation; the third was listed for transplantation but subsequently improved.

Measurement: Liver biopsy.

Results: Nefazodone was administered for 14 to 28 weeks before the onset of symptoms. The duration of jaundice before onset of encephalopathy ranged from 4 to 6 weeks. All cases of liver failure had similar histologic appearance, with prominent necrosis in the centrolobular areas (zone 3). One patient had successful liver transplantation, one underwent transplantation but died, and one improved without transplantation. The temporal onset of disease after the start of nefazodone therapy suggested severe hepatocellular injury caused by the drug.

Conclusions: Because nefazodone seems to cause severe hepatocellular injury in an idiosyncratic manner, routine liver chemistries should be performed before starting nefazodone therapy and patients should be monitored regularly. Therapy should be discontinued if liver enzyme concentrations become abnormal.

Author and Article Information

From University of Cincinnati and Children's Hospital Medical Center, Cincinnati, Ohio; and St. Louis University, St. Louis, Missouri.

Acknowledgments: The authors thank David Movick, MD, and Andrew Minkin, MD, for referring these patients.

Requests for Reprints: Fredrick L Weber Jr., MD, Liver Unit, Division of Digestive Diseases, University of Cincinnati Medical Center, 231 Bethesda Avenue, ML 595, Cincinnati, OH 45267.

Current Author Addresses: Drs. Aranda-Michel and Weber: Liver Unit, Division of Digestive Diseases, University of Cincinnati Medical Center, 231 Bethesda Avenue, ML 595, Cincinnati, OH 45267.

Drs. Koehler and Bejarano: Department of Pathology, University of Cincinnati Medical Center, 231 Bethesda Avenue, Cincinnati, OH 45267.

Drs. Poulos, Luxon, and Mobin Khan: Division of Gastroenterology and Hepatology, St. Louis University, 3635 Vista Avenue at Grand Boulevard, St. Louis, MO 63110.

Drs. Ee and Balistreri: Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229.