Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation

R. J. Fontana, T. M. McCashland, K. G. Benner, H. D. Appelman, N. T. Gunartanam, J. L. Wisecarver, J. M. Rabkin, W. M. Lee, H. Bodenheimer, E. Atillasoy, J. Rakela, O. Shakil, J. S. Crippin, K. G. Benner, H. R. Rosen, Paul Martin, R. Stribling, S. Flamm, A. T. Blei, A. Bass & 11 others S. D. Lidofsky, R. H. Wiesner, M. K. Porayko, J. E. Hay, M. G. Peters, A. Larson, K. Kowdley, Eugene R Schiff, A. G. Tzakis, M. J. Rodriguez, W. M. Lee

Research output: Contribution to journalArticle

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Abstract

Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

Original languageEnglish
Pages (from-to)480-484
Number of pages5
JournalLiver Transplantation and Surgery
Volume5
Issue number6
StatePublished - Nov 17 1999
Externally publishedYes

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Acute Liver Failure
Liver Transplantation
Hypoprothrombinemias
Non-Narcotic Analgesics
Liver Failure
Kidney Diseases
Transaminases
Tertiary Care Centers
Fatigue
bromfenac
Liver Diseases
Regeneration
Hypersensitivity
Emergencies
Anti-Inflammatory Agents
Necrosis
Transplantation
Clinical Trials
Liver
Wounds and Injuries

ASJC Scopus subject areas

  • Hepatology
  • Surgery

Cite this

Fontana, R. J., McCashland, T. M., Benner, K. G., Appelman, H. D., Gunartanam, N. T., Wisecarver, J. L., ... Lee, W. M. (1999). Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. Liver Transplantation and Surgery, 5(6), 480-484.

Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. / Fontana, R. J.; McCashland, T. M.; Benner, K. G.; Appelman, H. D.; Gunartanam, N. T.; Wisecarver, J. L.; Rabkin, J. M.; Lee, W. M.; Bodenheimer, H.; Atillasoy, E.; Rakela, J.; Shakil, O.; Crippin, J. S.; Benner, K. G.; Rosen, H. R.; Martin, Paul; Stribling, R.; Flamm, S.; Blei, A. T.; Bass, A.; Lidofsky, S. D.; Wiesner, R. H.; Porayko, M. K.; Hay, J. E.; Peters, M. G.; Larson, A.; Kowdley, K.; Schiff, Eugene R; Tzakis, A. G.; Rodriguez, M. J.; Lee, W. M.

In: Liver Transplantation and Surgery, Vol. 5, No. 6, 17.11.1999, p. 480-484.

Research output: Contribution to journalArticle

Fontana, RJ, McCashland, TM, Benner, KG, Appelman, HD, Gunartanam, NT, Wisecarver, JL, Rabkin, JM, Lee, WM, Bodenheimer, H, Atillasoy, E, Rakela, J, Shakil, O, Crippin, JS, Benner, KG, Rosen, HR, Martin, P, Stribling, R, Flamm, S, Blei, AT, Bass, A, Lidofsky, SD, Wiesner, RH, Porayko, MK, Hay, JE, Peters, MG, Larson, A, Kowdley, K, Schiff, ER, Tzakis, AG, Rodriguez, MJ & Lee, WM 1999, 'Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation', Liver Transplantation and Surgery, vol. 5, no. 6, pp. 480-484.
Fontana RJ, McCashland TM, Benner KG, Appelman HD, Gunartanam NT, Wisecarver JL et al. Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. Liver Transplantation and Surgery. 1999 Nov 17;5(6):480-484.
Fontana, R. J. ; McCashland, T. M. ; Benner, K. G. ; Appelman, H. D. ; Gunartanam, N. T. ; Wisecarver, J. L. ; Rabkin, J. M. ; Lee, W. M. ; Bodenheimer, H. ; Atillasoy, E. ; Rakela, J. ; Shakil, O. ; Crippin, J. S. ; Benner, K. G. ; Rosen, H. R. ; Martin, Paul ; Stribling, R. ; Flamm, S. ; Blei, A. T. ; Bass, A. ; Lidofsky, S. D. ; Wiesner, R. H. ; Porayko, M. K. ; Hay, J. E. ; Peters, M. G. ; Larson, A. ; Kowdley, K. ; Schiff, Eugene R ; Tzakis, A. G. ; Rodriguez, M. J. ; Lee, W. M. / Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. In: Liver Transplantation and Surgery. 1999 ; Vol. 5, No. 6. pp. 480-484.
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abstract = "Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.",
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T1 - Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation

AU - Fontana, R. J.

AU - McCashland, T. M.

AU - Benner, K. G.

AU - Appelman, H. D.

AU - Gunartanam, N. T.

AU - Wisecarver, J. L.

AU - Rabkin, J. M.

AU - Lee, W. M.

AU - Bodenheimer, H.

AU - Atillasoy, E.

AU - Rakela, J.

AU - Shakil, O.

AU - Crippin, J. S.

AU - Benner, K. G.

AU - Rosen, H. R.

AU - Martin, Paul

AU - Stribling, R.

AU - Flamm, S.

AU - Blei, A. T.

AU - Bass, A.

AU - Lidofsky, S. D.

AU - Wiesner, R. H.

AU - Porayko, M. K.

AU - Hay, J. E.

AU - Peters, M. G.

AU - Larson, A.

AU - Kowdley, K.

AU - Schiff, Eugene R

AU - Tzakis, A. G.

AU - Rodriguez, M. J.

AU - Lee, W. M.

PY - 1999/11/17

Y1 - 1999/11/17

N2 - Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

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