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
N1 - Funding Information:
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).
Funding Information:
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).
Publisher Copyright:
© 2021 AGA Institute
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 -