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Troglitazone-Induced Hepatic Failure Leading to Liver Transplantation: A Case Report

Brent A. Neuschwander-Tetri, MD; William L. Isley, MD; Julie C. Oki, PharmD; Sanjay Ramrakhiani, MD; Stella G. Quiason, MD; Nancy J. Phillips, MD; and Elizabeth M. Brunt, MD
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Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1998;129(1):38-41. doi:10.7326/0003-4819-129-1-199807010-00009
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Background: Troglitazone is a new drug for the treatment of type 2 diabetes. Although mild liver injury occurred in 1.9% of participants in controlled trials, the U.S. Food and Drug Administration has received reports of five postmarketing cases of severe liver disease that resulted in death or liver transplantation.

Objective: To report the clinical and histopathologic characteristics of a patient with troglitazone-associated severe liver injury leading to transplantation.

Design: Case report.

Setting: Two university hospitals.

Patient: A 55-year-old woman taking troglitazone, 400 mg/d, and insulin, 120 U/d.

Intervention: Discontinuation of troglitazone therapy, pretransplantation liver biopsy, and liver transplantation.

Results: Early nonspecific symptoms were attributed to other causes and were not evaluated. After the patient had used troglitazone for 3.5 months, massive loss of liver parenchyma and symptoms of liver failure developed, necessitating liver transplantation.

Conclusion: Troglitazone may cause subfulminant liver failure.

Figures

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Figure 1.
Liver histologic findings.Top.Middle.Bottom.

Photomicrographs were obtained from the explanted liver. Recent necrosis with hepatocyte dropout around a terminal hepatic venule in the lower left corner of the field is seen. No significant inflammation is present. Early collagen deposition is indicated by the light blue-green strands (Masson trichrome; original magnification, x20). In large portions of the explant, the parenchyma of the liver was replaced by the ductular proliferation and loose connective tissue, which can be seen adjacent to the residual hepatocytes in the upper portion of the field (Masson trichrome; original magnification, x10). Acinar collapse and early collagen deposition appear to bridge between two portal areas. Normal compact collagen (darker blue-green) surrounds the bile duct and portal vein within the portal tract and contrasts with the newly forming connective tissue in areas of hepatocyte dropout (Masson trichrome; original magnification, x10).

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