Diabetes Care, Vol 21, Issue 12 2140-2143, Copyright © 1998 by American Diabetes Association

ARTICLES

An autopsy case of troglitazone-induced fulminant hepatitis

A Shibuya, M Watanabe, Y Fujita, K Saigenji, S Kuwao, H Takahashi and H Takeuchi
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan. shibu-ya@ehp.kitasato-u.ac.jp

OBJECTIVE: To study an autopsy case of troglitazone-induced fulminant hepatitis. CASE REPORT: A 58-year-old man contracted severe hepatitis 2 months after administration of troglitazone for the treatment of type 2 diabetes. Liver damage progressed gradually, even after withdrawal of the agent. Despite intensive therapy, the hepatitis became fulminant and the patient died 8 weeks after the onset of liver damage. Autopsy revealed massive hepatic necrosis and cholestasis with inflammatory cell infiltration. The pathological findings and the positive result of the drug-induced lymphocyte stimulation test for troglitazone indicated that the liver damage was mediated by hypersensitivity to troglitazone. CONCLUSIONS: One report has attributed troglitazone-induced liver damage in less severe cases to idiosyncratic reactions. However, the present case indicates that troglitazone can induce hypersensitivity resulting in fulminant hepatitis. Careful monitoring of serum liver enzymes during troglitazone therapy is therefore essential.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Maniratanachote, K. Minami, M. Katoh, M. Nakajima, and T. Yokoi Chaperone Proteins Involved in Troglitazone-Induced Toxicity in Human Hepatoma Cell Lines Toxicol. Sci., February 1, 2005; 83(2): 293 - 302. [Abstract] [Full Text] [PDF]

				N. Brettenthaler, C. De Geyter, P. R. Huber, and U. Keller Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3835 - 3840. [Abstract] [Full Text] [PDF]

				J. P.H. van Wijk, E. J.P. de Koning, E. P. Martens, and T. J. Rabelink Thiazolidinediones and Blood Lipids in Type 2 Diabetes Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1744 - 1749. [Abstract] [Full Text] [PDF]

				D. M. Studdert, M. M. Mello, and T. A. Brennan Medical Monitoring for Pharmaceutical Injuries: Tort Law for the Public's Health? JAMA, February 19, 2003; 289(7): 889 - 894. [Abstract] [Full Text] [PDF]

				J D Tugwood and C T Montague Biology and toxicology of PPARg ligands Human and Experimental Toxicology, August 1, 2002; 21(8): 429 - 437. [Abstract] [PDF]

				H. E. Lebovitz, M. Kreider, and M. I. Freed Evaluation of Liver Function in Type 2 Diabetic Patients During Clinical Trials: Evidence that rosiglitazone does not cause hepatic dysfunction Diabetes Care, May 1, 2002; 25(5): 815 - 821. [Abstract] [Full Text] [PDF]

				V. E. Kostrubsky, M. Vore, E. Kindt, J. Burliegh, K. Rogers, G. Peter, D. Altrogge, and M. W. Sinz The Effect of Troglitazone Biliary Excretion on Metabolite Distribution and Cholestasis in Transporter-Deficient Rats Drug Metab. Dispos., December 1, 2001; 29(12): 1561 - 1566. [Abstract] [Full Text] [PDF]

				D. J. Graham, C. R. Drinkard, D. Shatin, Y. Tsong, and M. J. Burgess Liver Enzyme Monitoring in Patients Treated With Troglitazone JAMA, August 15, 2001; 286(7): 831 - 833. [Abstract] [Full Text] [PDF]

				R. Azziz, D. Ehrmann, R. S. Legro, R. W. Whitcomb, R. Hanley, A. G. Fereshetian, M. O’Keefe, and M. N. Ghazzi Troglitazone Improves Ovulation and Hirsutism in the Polycystic Ovary Syndrome: A Multicenter, Double Blind, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1626 - 1632. [Abstract] [Full Text]

				C. Funk, C. Ponelle, G. Scheuermann, and M. Pantze Cholestatic Potential of Troglitazone as a Possible Factor Contributing to Troglitazone-Induced Hepatotoxicity: In Vivo and in Vitro Interaction at the Canalicular Bile Salt Export Pump (Bsep) in the Rat Mol. Pharmacol., March 1, 2001; 59(3): 627 - 635. [Abstract] [Full Text]

				A. A. Parulkar, M. L. Pendergrass, R. Granda-Ayala, T. R. Lee, and V. A. Fonseca Nonhypoglycemic Effects of Thiazolidinediones Ann Intern Med, January 2, 2001; 134(1): 61 - 71. [Abstract] [Full Text] [PDF]

				M. J. Lenhard and W. B. Funk Failure to Develop Hepatic Injury From Rosiglitazone in a Patient With a History of Troglitazone-Induced Hepatitis Diabetes Care, January 1, 2001; 24(1): 168 - 169. [Full Text]

				K. A. Prendergast, C. L. Berg, and R. Wisniewski Troglitazone-Associated Hepatotoxicity Treated Successfully with Steroids Ann Intern Med, November 7, 2000; 133(9): 751 - 751. [Full Text] [PDF]

				V. E. Kostrubsky, J. F. Sinclair, V. Ramachandran, R. Venkataramanan, Y. H. Wen, E. Kindt, V. Galchev, K. Rose, M. Sinz, and S. C. Strom The Role of Conjugation in Hepatotoxicity of Troglitazone in Human and Porcine Hepatocyte Cultures Drug Metab. Dispos., October 1, 2000; 28(10): 1192 - 1197. [Abstract] [Full Text] [PDF]

				E. Arioglu, J. Duncan-Morin, N. Sebring, K. I. Rother, N. Gottlieb, J. Lieberman, D. Herion, D. E. Kleiner, J. Reynolds, A. Premkumar, et al. Efficacy and Safety of Troglitazone in the Treatment of Lipodystrophy Syndromes Ann Intern Med, August 15, 2000; 133(4): 263 - 274. [Abstract] [Full Text] [PDF]

				J. Al-Salman, H. Arjomand, D. G. Kemp, and M. Mittal Hepatocellular Injury in a Patient Receiving Rosiglitazone: A Case Report Ann Intern Med, January 18, 2000; 132(2): 121 - 124. [Abstract] [Full Text] [PDF]