Stephen H. Caldwell, MD
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Caldwell SH. Efficacy and Safety of Troglitazone for Lipodystrophy Syndromes. Ann Intern Med. 2001;134:1008. doi: 10.7326/0003-4819-134-10-200105150-00016
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Published: Ann Intern Med. 2001;134(10):1008.
TO THE EDITOR:
Arioglu and colleagues (1) discussed the association between lipodystrophy and nonalcoholic steatohepatitis (NASH) and the effects of troglitazone. We recently reported on a pilot study of troglitazone for NASH (2) that began before idiosyncratic hepatotoxicity was recognized and troglitazone was withdrawn from the U.S. market.
In our study, liver enzyme levels normalized in 7 of 10 patients after 4 to 6 months of troglitazone therapy. This was associated with mild improvement in the histologic score for inflammation on end-of-treatment biopsy samples. However, electron microscopy showed a tendency toward increased mitochondrial morphologic abnormalities, including swelling and development of intramitochondrial crystals, after troglitazone therapy. These abnormalities occur in 5% to 10% of hepatocyte mitochondria in patients with NASH at baseline and probably correlate with an increased state of mitochondrial uncoupling (3). Cortez-Pinto and colleagues showed increased expression of uncoupling protein in obese mice with fatty liver and found abnormal adenosine triphosphate homeostasis in humans with NASH (4). Our findings suggested that troglitazone accentuates underlying mitochondrial abnormalities in NASH. This change may predispose to severe liver injury in situations of metabolic stress.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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