Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study

US Acute Liver Failure Study Group

doi:10.1016/j.cgh.2020.09.016

Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study

US Acute Liver Failure Study Group

Medicine, Hepatology Division

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

18 Scopus citations

Abstract

Background & Aims: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. Methods: A retrospective review of this prospective, multicenter cohort study of all APAP–ALF patients enrolled during the study period (1998–2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998–2007; recent, 2008–2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). Results: Of 1190 APAP–ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). Conclusions: TFS in APAP–ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

Original language	English (US)
Pages (from-to)	2615-2625.e3
Journal	Clinical Gastroenterology and Hepatology
Volume	19
Issue number	12
DOIs	https://doi.org/10.1016/j.cgh.2020.09.016
State	Published - Dec 2021

Funding

Funding This study was sponsored by National Institutes of Health grant U-01 58369 (from the National Institute of Diabetes and Digestive and Kidney Diseases). Conflicts of interest This author discloses the following: William M. Lee receives research support from Merck, Conatus, Intercept, Bristol-Myers Squibb, Novo Nordisk, Synlogic, Eiger, Cumberland, Exalenz, Instrumentation Laboratory, and Ocera Therapeutics (now Mallinkrodt Pharmaceuticals), and has received personal fees for consulting from Forma, Sanofi, Seattle Genetics, Affibody, Karuna, and Genentech. The remaining authors disclose no conflicts. Funding This study was sponsored by National Institutes of Health grant U-01 58369 (from the National Institute of Diabetes and Digestive and Kidney Diseases).

Keywords

Cerebral Edema
Continuous Renal Replacement Therapy Intracranial Hypertension
Transplant-Free Survival
Transplantation

ASJC Scopus subject areas

Gastroenterology
Hepatology

Access to Document

10.1016/j.cgh.2020.09.016

Cite this

@article{3959dd065c2d4e728e63244a922aabd6,

title = "Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study",

abstract = "Background & Aims: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. Methods: A retrospective review of this prospective, multicenter cohort study of all APAP–ALF patients enrolled during the study period (1998–2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998–2007; recent, 2008–2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). Results: Of 1190 APAP–ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). Conclusions: TFS in APAP–ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.",

keywords = "Cerebral Edema, Continuous Renal Replacement Therapy Intracranial Hypertension, Transplant-Free Survival, Transplantation",

author = "{US Acute Liver Failure Study Group} and MacDonald, {Andrew J.} and Speiser, {Jaime L.} and Ganger, {Daniel R.} and Nilles, {Kathleen M.} and Orandi, {Babak J.} and Larson, {Anne M.} and Lee, {William M.} and Karvellas, {Constantine J.} and Iris Liou and Oren Fix and Michael Schilsky and Timothy McCashland and {Eileen Hay}, J. and Natalie Murray and Shaikh, {A. Obaid S.} and Andres Blei and Daniel Ganger and Atif Zaman and Han, {Steven H.B.} and {Robert Fontana}, 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 {Todd Stravitz}, R. and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein and Jodi Olson and Ram Subramanian and James Hanje and Bilal Hameed",

note = "Publisher Copyright: {\textcopyright} 2021 AGA Institute",

year = "2021",

month = dec,

doi = "10.1016/j.cgh.2020.09.016",

language = "English (US)",

volume = "19",

pages = "2615--2625.e3",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "12",

}

TY - JOUR

T1 - Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure

T2 - A 21-Year Multicenter Cohort Study

AU - US Acute Liver Failure Study Group

AU - MacDonald, Andrew J.

AU - Speiser, Jaime L.

AU - Ganger, Daniel R.

AU - Nilles, Kathleen M.

AU - Orandi, Babak J.

AU - Larson, Anne M.

AU - Lee, William M.

AU - Karvellas, Constantine J.

AU - Liou, Iris

AU - Fix, Oren

AU - Schilsky, Michael

AU - McCashland, Timothy

AU - Eileen Hay, J.

AU - Murray, Natalie

AU - Shaikh, A. Obaid S.

AU - Blei, Andres

AU - Ganger, Daniel

AU - Zaman, Atif

AU - Han, Steven H.B.

AU - Robert Fontana, Fontana

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 - Todd Stravitz, R.

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

AU - Olson, Jodi

AU - Subramanian, Ram

AU - Hanje, James

AU - Hameed, Bilal

PY - 2021/12

Y1 - 2021/12

N2 - Background & Aims: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. Methods: A retrospective review of this prospective, multicenter cohort study of all APAP–ALF patients enrolled during the study period (1998–2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998–2007; recent, 2008–2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). Results: Of 1190 APAP–ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). Conclusions: TFS in APAP–ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

AB - Background & Aims: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. Methods: A retrospective review of this prospective, multicenter cohort study of all APAP–ALF patients enrolled during the study period (1998–2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998–2007; recent, 2008–2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). Results: Of 1190 APAP–ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). Conclusions: TFS in APAP–ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

KW - Cerebral Edema

KW - Continuous Renal Replacement Therapy Intracranial Hypertension

KW - Transplant-Free Survival

KW - Transplantation

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U2 - 10.1016/j.cgh.2020.09.016

DO - 10.1016/j.cgh.2020.09.016

M3 - Article

C2 - 32920216

AN - SCOPUS:85097222153

SN - 1542-3565

VL - 19

SP - 2615-2625.e3

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 12

ER -

Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study

Abstract

Funding

Keywords

ASJC Scopus subject areas

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