Outcomes in adults with acute liver failure between 1998 and 2013

An observational cohort study

Adrian Reuben, Holly Tillman, Robert J. Fontana, Timothy Davern, Brendan Mcguire, R. Todd Stravitz, Valerie Durkalski, Anne M. Larson, Iris Liou, Oren Fix, Michael Schilsky, Timothy Mccashland, J. Eileen Hay, Natalie Murray, Obaid S. Shaikh, Daniel Ganger, Atif Zaman, Steven B. Han, Raymond T. Chung, Alastair Smith & 17 others Robert Brown, Jeffrey Crippin, M. Edwyn Harrison, David Koch, Santiago Munoz, K. Rajender Reddy, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, A. James Hanje, Jody Olson, Ram Subramanian, Constantine Karvellas, Bilal Hameed, Averell H. Sherker, Patricia Robuck, William M. Lee

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440) Setting: 31 liver disease and transplant centers in the United States. Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P <0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P <0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study.

Original languageEnglish (US)
Pages (from-to)724-732
Number of pages9
JournalAnnals of Internal Medicine
Volume164
Issue number11
DOIs
StatePublished - Jun 7 2016

Fingerprint

Acute Liver Failure
Observational Studies
Cohort Studies
Survival
Transplants
Liver Diseases
Critical Care
Acetylcysteine
Acetaminophen
Artificial Respiration
Tertiary Care Centers
Liver Transplantation
Survival Rate
Erythrocytes
Morbidity
Mortality
Liver
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Outcomes in adults with acute liver failure between 1998 and 2013 : An observational cohort study. / Reuben, Adrian; Tillman, Holly; Fontana, Robert J.; Davern, Timothy; Mcguire, Brendan; Stravitz, R. Todd; Durkalski, Valerie; Larson, Anne M.; Liou, Iris; Fix, Oren; Schilsky, Michael; Mccashland, Timothy; Hay, J. Eileen; Murray, Natalie; Shaikh, Obaid S.; Ganger, Daniel; Zaman, Atif; Han, Steven B.; Chung, Raymond T.; Smith, Alastair; Brown, Robert; Crippin, Jeffrey; Harrison, M. Edwyn; Koch, David; Munoz, Santiago; Reddy, K. Rajender; Rossaro, Lorenzo; Satyanarayana, Raj; Hassanein, Tarek; Hanje, A. James; Olson, Jody; Subramanian, Ram; Karvellas, Constantine; Hameed, Bilal; Sherker, Averell H.; Robuck, Patricia; Lee, William M.

In: Annals of Internal Medicine, Vol. 164, No. 11, 07.06.2016, p. 724-732.

Research output: Contribution to journalArticle

Reuben, A, Tillman, H, Fontana, RJ, Davern, T, Mcguire, B, Stravitz, RT, Durkalski, V, Larson, AM, Liou, I, Fix, O, Schilsky, M, Mccashland, T, Hay, JE, Murray, N, Shaikh, OS, Ganger, D, Zaman, A, Han, SB, Chung, RT, Smith, A, Brown, R, Crippin, J, Harrison, ME, Koch, D, Munoz, S, Reddy, KR, Rossaro, L, Satyanarayana, R, Hassanein, T, Hanje, AJ, Olson, J, Subramanian, R, Karvellas, C, Hameed, B, Sherker, AH, Robuck, P & Lee, WM 2016, 'Outcomes in adults with acute liver failure between 1998 and 2013: An observational cohort study', Annals of Internal Medicine, vol. 164, no. 11, pp. 724-732. https://doi.org/10.7326/M15-2211
Reuben A, Tillman H, Fontana RJ, Davern T, Mcguire B, Stravitz RT et al. Outcomes in adults with acute liver failure between 1998 and 2013: An observational cohort study. Annals of Internal Medicine. 2016 Jun 7;164(11):724-732. https://doi.org/10.7326/M15-2211
Reuben, Adrian ; Tillman, Holly ; Fontana, Robert J. ; Davern, Timothy ; Mcguire, Brendan ; Stravitz, R. Todd ; Durkalski, Valerie ; Larson, Anne M. ; Liou, Iris ; Fix, Oren ; Schilsky, Michael ; Mccashland, Timothy ; Hay, J. Eileen ; Murray, Natalie ; Shaikh, Obaid S. ; Ganger, Daniel ; Zaman, Atif ; Han, Steven B. ; Chung, Raymond T. ; Smith, Alastair ; Brown, Robert ; Crippin, Jeffrey ; Harrison, M. Edwyn ; Koch, David ; Munoz, Santiago ; Reddy, K. Rajender ; Rossaro, Lorenzo ; Satyanarayana, Raj ; Hassanein, Tarek ; Hanje, A. James ; Olson, Jody ; Subramanian, Ram ; Karvellas, Constantine ; Hameed, Bilal ; Sherker, Averell H. ; Robuck, Patricia ; Lee, William M. / Outcomes in adults with acute liver failure between 1998 and 2013 : An observational cohort study. In: Annals of Internal Medicine. 2016 ; Vol. 164, No. 11. pp. 724-732.
@article{546b45328bbb4582bbc08845f2c511b1,
title = "Outcomes in adults with acute liver failure between 1998 and 2013: An observational cohort study",
abstract = "Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440) Setting: 31 liver disease and transplant centers in the United States. Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1{\%} vs. 75.3{\%}; transplant-free survival [TFS], 45.1{\%} vs. 56.2{\%}; posttransplantation survival, 88.3{\%} vs. 96.3{\%} [P <0.010 for each]). Reductions in red blood cell infusions (44.3{\%} vs. 27.6{\%}), plasma infusions (65.2{\%} vs. 47.1{\%}), mechanical ventilation (65.7{\%} vs. 56.1{\%}), and vasopressors (34.9{\%} vs. 27.8{\%}) were observed, as well as increased use of N-acetylcysteine (48.9{\%} vs. 69.3{\%} overall; 15.8{\%} vs. 49.4{\%} [P <0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study.",
author = "Adrian Reuben and Holly Tillman and Fontana, {Robert J.} and Timothy Davern and Brendan Mcguire and Stravitz, {R. Todd} and Valerie Durkalski and Larson, {Anne M.} and Iris Liou and Oren Fix and Michael Schilsky and Timothy Mccashland and Hay, {J. Eileen} and Natalie Murray and Shaikh, {Obaid S.} and Daniel Ganger and Atif Zaman and Han, {Steven B.} and Chung, {Raymond T.} and Alastair Smith and Robert Brown and Jeffrey Crippin and Harrison, {M. Edwyn} and David Koch and Santiago Munoz and Reddy, {K. Rajender} and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein and Hanje, {A. James} and Jody Olson and Ram Subramanian and Constantine Karvellas and Bilal Hameed and Sherker, {Averell H.} and Patricia Robuck and Lee, {William M.}",
year = "2016",
month = "6",
day = "7",
doi = "10.7326/M15-2211",
language = "English (US)",
volume = "164",
pages = "724--732",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "11",

}

TY - JOUR

T1 - Outcomes in adults with acute liver failure between 1998 and 2013

T2 - An observational cohort study

AU - Reuben, Adrian

AU - Tillman, Holly

AU - Fontana, Robert J.

AU - Davern, Timothy

AU - Mcguire, Brendan

AU - Stravitz, R. Todd

AU - Durkalski, Valerie

AU - Larson, Anne M.

AU - Liou, Iris

AU - Fix, Oren

AU - Schilsky, Michael

AU - Mccashland, Timothy

AU - Hay, J. Eileen

AU - Murray, Natalie

AU - Shaikh, Obaid S.

AU - Ganger, Daniel

AU - Zaman, Atif

AU - Han, Steven B.

AU - Chung, Raymond T.

AU - Smith, Alastair

AU - Brown, Robert

AU - Crippin, Jeffrey

AU - Harrison, M. Edwyn

AU - Koch, David

AU - Munoz, Santiago

AU - Reddy, K. Rajender

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

AU - Hanje, A. James

AU - Olson, Jody

AU - Subramanian, Ram

AU - Karvellas, Constantine

AU - Hameed, Bilal

AU - Sherker, Averell H.

AU - Robuck, Patricia

AU - Lee, William M.

PY - 2016/6/7

Y1 - 2016/6/7

N2 - Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440) Setting: 31 liver disease and transplant centers in the United States. Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P <0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P <0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study.

AB - Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440) Setting: 31 liver disease and transplant centers in the United States. Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P <0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P <0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study.

UR - http://www.scopus.com/inward/record.url?scp=84973461644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973461644&partnerID=8YFLogxK

U2 - 10.7326/M15-2211

DO - 10.7326/M15-2211

M3 - Article

VL - 164

SP - 724

EP - 732

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 11

ER -