Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure

William M. Lee, Linda S. Hynan, Lorenzo Rossaro, Robert J. Fontana, R. Todd Stravitz, Anne M. Larson, Timothy J. Davern, Natalie G. Murray, Timothy McCashland, Joan S. Reisch, Patricia R. Robuck

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Abstract

Background & Aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

Original languageEnglish (US)
JournalGastroenterology
Volume137
Issue number3
DOIs
StatePublished - Sep 2009

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Acute Liver Failure
Acetylcysteine
Transplants
Survival
Placebos
Coma
Acetaminophen
Transplantation
Antidotes
Liver Transplantation
Poisoning
Nausea
Vomiting
Emergencies
Survival Rate

ASJC Scopus subject areas

  • Gastroenterology

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Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure. / Lee, William M.; Hynan, Linda S.; Rossaro, Lorenzo; Fontana, Robert J.; Stravitz, R. Todd; Larson, Anne M.; Davern, Timothy J.; Murray, Natalie G.; McCashland, Timothy; Reisch, Joan S.; Robuck, Patricia R.

In: Gastroenterology, Vol. 137, No. 3, 09.2009.

Research output: Contribution to journalArticle

Lee, William M. ; Hynan, Linda S. ; Rossaro, Lorenzo ; Fontana, Robert J. ; Stravitz, R. Todd ; Larson, Anne M. ; Davern, Timothy J. ; Murray, Natalie G. ; McCashland, Timothy ; Reisch, Joan S. ; Robuck, Patricia R. / Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure. In: Gastroenterology. 2009 ; Vol. 137, No. 3.
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title = "Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure",
abstract = "Background & Aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70{\%} for patients given NAC and 66{\%} for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40{\%}) than for those given placebo (27{\%}; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52{\%} compared with 30{\%} for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9{\%} in those given NAC and 22{\%} in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32{\%} vs 45{\%}; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14{\%} vs 4{\%}; P = .031). Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.",
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T1 - Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure

AU - Lee, William M.

AU - Hynan, Linda S.

AU - Rossaro, Lorenzo

AU - Fontana, Robert J.

AU - Stravitz, R. Todd

AU - Larson, Anne M.

AU - Davern, Timothy J.

AU - Murray, Natalie G.

AU - McCashland, Timothy

AU - Reisch, Joan S.

AU - Robuck, Patricia R.

PY - 2009/9

Y1 - 2009/9

N2 - Background & Aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

AB - Background & Aims: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. Methods: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. Results: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Conclusions: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

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U2 - 10.1053/j.gastro.2009.06.006

DO - 10.1053/j.gastro.2009.06.006

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