Special articleTroglitazone-induced liver failure: a case study☆
Section snippets
Methods
All domestic cases of hospitalized or fatal liver injury associated with troglitazone that were voluntarily reported to the FDA were reviewed. Follow-up information was sought from reporting physicians to capture missing clinical details. Case data were abstracted describing patient demographic characteristics, dose and duration of troglitazone therapy, other treatments for diabetes, time of onset and progression of symptoms of hepatic failure, outcome, and pathology results, when available.
Results
Ninety-four cases of liver failure (89 acute, 5 chronic) in association with troglitazone use were reported. About two thirds of the patients with acute liver failure were women (Table 1). The onset of liver injury began from 3 days to after more than 2 years of troglitazone use. Viral hepatitis testing was reported in 57 patients (64%), with prior infection noted in 17 patients (hepatitis A: 6; hepatitis B: 8; hepatitis A and B: 2; hepatitis C: 1). Monitoring of hepatic enzymes, either at the
Discussion
Ninety-four cases of troglitazone-induced liver failure were reported to the FDA, of which 89 (95%) were acute. The ages of these patients were similar to those seen in patients with type 2 diabetes, but women were overrepresented (43), as has been observed with other hepatotoxins (44). Consistent with the literature 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 45, 46, 47, 48, 49, most patients in this series had hepatocellular damage, although cholestatic and mixed presentations were also observed.
Acknowledgements
We thank Carol R. Drinkard, PhD, and Deborah Shatin, PhD, of the Center for Health Care Policy and Evaluation, UnitedHealth Group, for providing the cohort data used in this study; Curt Furberg, MD, PhD, and Paul Stolley, MD, MPH, for constructive suggestions; and Robert T. O’Neill, PhD, for statistical review of the methods used in this study.
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This study was supported in part by cooperative agreements FD-U-000149 and FD-U-0001643-01/02 with the U.S. Food and Drug Administration, Rockville, Maryland.