Steroid use in acute liver failure

Jamuna Karkhanis, Elizabeth C. Verna, Matthew S. Chang, R. Todd Stravitz, Michael Schilsky, William M. Lee, Robert S. Brown, George A. Ostapowicz, Frank V. Schiødt, Julie Polson, Anne M. Larson, Timothy Davern, Timothy M McCashland, J. Eileen Hay, Natalie Murray, A. Obaid S Shaikh, Andres Blei, Atif Zaman, Steven H B Han, Robert FontanaBrendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Grace Samuel, Ezmina Lalani, Carla Pezzia, Corron Sanders, Joan S. Reisch, Linda S. Hynan, Janet P. Smith, Joe W. Webster, Mechelle Murray

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%, P=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P=0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH<7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%, P=0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. Conclusion: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.

Original languageEnglish (US)
Pages (from-to)612-621
Number of pages10
JournalHepatology
Volume59
Issue number2
DOIs
StatePublished - Feb 1 2014

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Acute Liver Failure
Steroids
Survival
Odds Ratio
Liver Diseases
Autoimmune Hepatitis
Adrenal Cortex Hormones
Pharmaceutical Preparations
Multivariate Analysis
Coma
Alanine Transaminase
Artificial Respiration
Transplants

ASJC Scopus subject areas

  • Hepatology

Cite this

Karkhanis, J., Verna, E. C., Chang, M. S., Stravitz, R. T., Schilsky, M., Lee, W. M., ... Murray, M. (2014). Steroid use in acute liver failure. Hepatology, 59(2), 612-621. https://doi.org/10.1002/hep.26678

Steroid use in acute liver failure. / Karkhanis, Jamuna; Verna, Elizabeth C.; Chang, Matthew S.; Stravitz, R. Todd; Schilsky, Michael; Lee, William M.; Brown, Robert S.; Ostapowicz, George A.; Schiødt, Frank V.; Polson, Julie; Larson, Anne M.; Davern, Timothy; McCashland, Timothy M; Eileen Hay, J.; Murray, Natalie; Shaikh, A. Obaid S; Blei, Andres; Zaman, Atif; Han, Steven H B; Fontana, Robert; McGuire, Brendan; Chung, Raymond T.; Smith, Alastair; Brown, Robert; Crippin, Jeffrey; Harrison, Edwin; Reuben, Adrian; Munoz, Santiago; Reddy, Rajender; Rossaro, Lorenzo; Satyanarayana, Raj; Hassanein, Tarek; Samuel, Grace; Lalani, Ezmina; Pezzia, Carla; Sanders, Corron; Reisch, Joan S.; Hynan, Linda S.; Smith, Janet P.; Webster, Joe W.; Murray, Mechelle.

In: Hepatology, Vol. 59, No. 2, 01.02.2014, p. 612-621.

Research output: Contribution to journalArticle

Karkhanis, J, Verna, EC, Chang, MS, Stravitz, RT, Schilsky, M, Lee, WM, Brown, RS, Ostapowicz, GA, Schiødt, FV, Polson, J, Larson, AM, Davern, T, McCashland, TM, Eileen Hay, J, Murray, N, Shaikh, AOS, Blei, A, Zaman, A, Han, SHB, Fontana, R, McGuire, B, Chung, RT, Smith, A, Brown, R, Crippin, J, Harrison, E, Reuben, A, Munoz, S, Reddy, R, Rossaro, L, Satyanarayana, R, Hassanein, T, Samuel, G, Lalani, E, Pezzia, C, Sanders, C, Reisch, JS, Hynan, LS, Smith, JP, Webster, JW & Murray, M 2014, 'Steroid use in acute liver failure', Hepatology, vol. 59, no. 2, pp. 612-621. https://doi.org/10.1002/hep.26678
Karkhanis J, Verna EC, Chang MS, Stravitz RT, Schilsky M, Lee WM et al. Steroid use in acute liver failure. Hepatology. 2014 Feb 1;59(2):612-621. https://doi.org/10.1002/hep.26678
Karkhanis, Jamuna ; Verna, Elizabeth C. ; Chang, Matthew S. ; Stravitz, R. Todd ; Schilsky, Michael ; Lee, William M. ; Brown, Robert S. ; Ostapowicz, George A. ; Schiødt, Frank V. ; Polson, Julie ; Larson, Anne M. ; Davern, Timothy ; McCashland, Timothy M ; Eileen Hay, J. ; Murray, Natalie ; Shaikh, A. Obaid S ; Blei, Andres ; Zaman, Atif ; Han, Steven H B ; Fontana, Robert ; McGuire, Brendan ; Chung, Raymond T. ; Smith, Alastair ; Brown, Robert ; Crippin, Jeffrey ; Harrison, Edwin ; Reuben, Adrian ; Munoz, Santiago ; Reddy, Rajender ; Rossaro, Lorenzo ; Satyanarayana, Raj ; Hassanein, Tarek ; Samuel, Grace ; Lalani, Ezmina ; Pezzia, Carla ; Sanders, Corron ; Reisch, Joan S. ; Hynan, Linda S. ; Smith, Janet P. ; Webster, Joe W. ; Murray, Mechelle. / Steroid use in acute liver failure. In: Hepatology. 2014 ; Vol. 59, No. 2. pp. 612-621.
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abstract = "Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61{\%} versus 66{\%}, P=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30{\%} versus 57{\%}, P=0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH<7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35{\%} versus 23{\%}, P=0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. Conclusion: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.",
author = "Jamuna Karkhanis and Verna, {Elizabeth C.} and Chang, {Matthew S.} and Stravitz, {R. Todd} and Michael Schilsky and Lee, {William M.} and Brown, {Robert S.} and Ostapowicz, {George A.} and Schi{\o}dt, {Frank V.} and Julie Polson and Larson, {Anne M.} and Timothy Davern and McCashland, {Timothy M} and {Eileen Hay}, J. and Natalie Murray and Shaikh, {A. Obaid S} and Andres Blei and Atif Zaman and Han, {Steven H B} and Robert Fontana and Brendan McGuire and Chung, {Raymond T.} and Alastair Smith and Robert Brown and Jeffrey Crippin and Edwin Harrison and Adrian Reuben and Santiago Munoz and Rajender Reddy and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein and Grace Samuel and Ezmina Lalani and Carla Pezzia and Corron Sanders and Reisch, {Joan S.} and Hynan, {Linda S.} and Smith, {Janet P.} and Webster, {Joe W.} and Mechelle Murray",
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T1 - Steroid use in acute liver failure

AU - Karkhanis, Jamuna

AU - Verna, Elizabeth C.

AU - Chang, Matthew S.

AU - Stravitz, R. Todd

AU - Schilsky, Michael

AU - Lee, William M.

AU - Brown, Robert S.

AU - Ostapowicz, George A.

AU - Schiødt, Frank V.

AU - Polson, Julie

AU - Larson, Anne M.

AU - Davern, Timothy

AU - McCashland, Timothy M

AU - Eileen Hay, J.

AU - Murray, Natalie

AU - Shaikh, A. Obaid S

AU - Blei, Andres

AU - Zaman, Atif

AU - Han, Steven H B

AU - Fontana, Robert

AU - McGuire, Brendan

AU - Chung, Raymond T.

AU - Smith, Alastair

AU - Brown, Robert

AU - Crippin, Jeffrey

AU - Harrison, Edwin

AU - Reuben, Adrian

AU - Munoz, Santiago

AU - Reddy, Rajender

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

AU - Samuel, Grace

AU - Lalani, Ezmina

AU - Pezzia, Carla

AU - Sanders, Corron

AU - Reisch, Joan S.

AU - Hynan, Linda S.

AU - Smith, Janet P.

AU - Webster, Joe W.

AU - Murray, Mechelle

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%, P=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P=0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH<7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%, P=0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. Conclusion: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.

AB - Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%, P=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P=0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH<7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%, P=0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. Conclusion: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.

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