Troglitazone-induced fulminant hepatic failure

Elizabeth J. Murphy; Timothy J. Davern; A. Obaid Shakil; Lawton Shick; Umesh Masharani; Hsichao Chow; Chris Freise; William M. Lee; Nathan M. Bass; George Ostapowicz; Anne Larson; Cary Caldwell; Marion Peters; Smita Rouillard; Evren Atillasoy; Henry Bodenheimer; Thomas Schiano; Tim McCashland; J. Eileen Hay; Russell Wiesner; Jeffrey Crippin; Tom Faust; Jorge Rakela; Andres Blei; Steven Flamm; Kent Benner; Steven Huy Bui Han; Paul Martin; Risë Stribling; Eugene Schiff; Robert Fontana

doi:10.1023/A:1005405526283

Troglitazone-induced fulminant hepatic failure

Elizabeth J. Murphy, Timothy J. Davern, A. Obaid Shakil, Lawton Shick, Umesh Masharani, Hsichao Chow, Chris Freise, William M. Lee, Nathan M. Bass, George Ostapowicz, Anne Larson, Cary Caldwell, Marion Peters, Smita Rouillard, Evren Atillasoy, Henry Bodenheimer, Thomas Schiano, Tim McCashland, J. Eileen Hay, Russell WiesnerJeffrey Crippin, Tom Faust, Jorge Rakela, Andres Blei, Steven Flamm, Kent Benner, Steven Huy Bui Han, Paul Martin, Risë Stribling, Eugene Schiff, Robert Fontana

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date (5-7), the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

Original language	English (US)
Pages (from-to)	549-553
Number of pages	5
Journal	Digestive Diseases and Sciences
Volume	45
Issue number	3
DOIs	https://doi.org/10.1023/A:1005405526283
State	Published - 2000

Keywords

Adverse effects
Diabetes mellitus
Liver failure
Liver transplantation
Thiazoles
Toxic hepatitis
Troglitazone

ASJC Scopus subject areas

Physiology
Gastroenterology

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10.1023/A:1005405526283

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Murphy, E. J., Davern, T. J., Obaid Shakil, A., Shick, L., Masharani, U., Chow, H., Freise, C., Lee, W. M., Bass, N. M., Ostapowicz, G., Larson, A., Caldwell, C., Peters, M., Rouillard, S., Atillasoy, E., Bodenheimer, H., Schiano, T., McCashland, T., Hay, J. E., ... Fontana, R. (2000). Troglitazone-induced fulminant hepatic failure. Digestive Diseases and Sciences, 45(3), 549-553. https://doi.org/10.1023/A:1005405526283

Murphy, EJ, Davern, TJ, Obaid Shakil, A, Shick, L, Masharani, U, Chow, H, Freise, C, Lee, WM, Bass, NM, Ostapowicz, G, Larson, A, Caldwell, C, Peters, M, Rouillard, S, Atillasoy, E, Bodenheimer, H, Schiano, T, McCashland, T, Hay, JE, Wiesner, R, Crippin, J, Faust, T, Rakela, J, Blei, A, Flamm, S, Benner, K, Han, SHB, Martin, P, Stribling, R, Schiff, E & Fontana, R 2000, 'Troglitazone-induced fulminant hepatic failure', Digestive Diseases and Sciences, vol. 45, no. 3, pp. 549-553. https://doi.org/10.1023/A:1005405526283

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title = "Troglitazone-induced fulminant hepatic failure",

abstract = "The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date (5-7), the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.",

keywords = "Adverse effects, Diabetes mellitus, Liver failure, Liver transplantation, Thiazoles, Toxic hepatitis, Troglitazone",

author = "Murphy, {Elizabeth J.} and Davern, {Timothy J.} and {Obaid Shakil}, A. and Lawton Shick and Umesh Masharani and Hsichao Chow and Chris Freise and Lee, {William M.} and Bass, {Nathan M.} and George Ostapowicz and Anne Larson and Cary Caldwell and Marion Peters and Smita Rouillard and Evren Atillasoy and Henry Bodenheimer and Thomas Schiano and Tim McCashland and Hay, {J. Eileen} and Russell Wiesner and Jeffrey Crippin and Tom Faust and Jorge Rakela and Andres Blei and Steven Flamm and Kent Benner and Han, {Steven Huy Bui} and Paul Martin and Ris{\"e} Stribling and Eugene Schiff and Robert Fontana",

note = "Funding Information: This work was sponsored in part by NIH grant (R03 DK5287-01) in support of the Acute Liver Failure Study Group.",

year = "2000",

doi = "10.1023/A:1005405526283",

language = "English (US)",

volume = "45",

pages = "549--553",

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AU - Murphy, Elizabeth J.

AU - Davern, Timothy J.

AU - Obaid Shakil, A.

AU - Shick, Lawton

AU - Masharani, Umesh

AU - Chow, Hsichao

AU - Freise, Chris

AU - Lee, William M.

AU - Bass, Nathan M.

AU - Ostapowicz, George

AU - Larson, Anne

AU - Caldwell, Cary

AU - Peters, Marion

AU - Rouillard, Smita

AU - Atillasoy, Evren

AU - Bodenheimer, Henry

AU - Schiano, Thomas

AU - McCashland, Tim

AU - Hay, J. Eileen

AU - Wiesner, Russell

AU - Crippin, Jeffrey

AU - Faust, Tom

AU - Rakela, Jorge

AU - Blei, Andres

AU - Flamm, Steven

AU - Benner, Kent

AU - Han, Steven Huy Bui

AU - Martin, Paul

AU - Stribling, Risë

AU - Schiff, Eugene

AU - Fontana, Robert

N1 - Funding Information: This work was sponsored in part by NIH grant (R03 DK5287-01) in support of the Acute Liver Failure Study Group.

PY - 2000

Y1 - 2000

N2 - The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date (5-7), the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

AB - The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date (5-7), the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

KW - Adverse effects

KW - Diabetes mellitus

KW - Liver failure

KW - Liver transplantation

KW - Thiazoles

KW - Toxic hepatitis

KW - Troglitazone

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JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

IS - 3

ER -

Troglitazone-induced fulminant hepatic failure

Abstract

Keywords

ASJC Scopus subject areas

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