Document Detail


Development of an accurate index for predicting outcomes of patients with acute liver failure.
MedLine Citation:
PMID:  22885329     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF.
METHODS: Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices.
RESULTS: Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF.
CONCLUSIONS: The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD.
Authors:
Anna Rutherford; Lindsay Y King; Linda S Hynan; Chetan Vedvyas; Wenyu Lin; William M Lee; Raymond T Chung;
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2012-08-08
Journal Detail:
Title:  Gastroenterology     Volume:  143     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-14     Revised Date:  2014-06-06    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1237-43     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00518440
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Area Under Curve
Bilirubin / blood
Chi-Square Distribution
Coma / etiology
End Stage Liver Disease / surgery
Female
Humans
International Normalized Ratio
Keratin-18 / blood*
Liver Failure, Acute / blood*,  complications,  surgery
Liver Transplantation
Logistic Models
Male
Middle Aged
Odds Ratio
Peptide Fragments / blood*
Predictive Value of Tests
ROC Curve
Severity of Illness Index*
Statistics, Nonparametric
Survival Analysis
Young Adult
Grant Support
ID/Acronym/Agency:
K24 DK078772/DK/NIDDK NIH HHS; K24 DK078772/DK/NIDDK NIH HHS; R21 DK077716/DK/NIDDK NIH HHS; R21DK077716/DK/NIDDK NIH HHS; T32 DK007191/DK/NIDDK NIH HHS; U01 DK058369/DK/NIDDK NIH HHS; U01DK58369/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Keratin-18; 0/M30 cytokeratin-18 peptide, human; 0/M65 antigen, human; 0/Peptide Fragments; RFM9X3LJ49/Bilirubin
Comments/Corrections
Comment In:
Gastroenterology. 2013 Jan;144(1):e25   [PMID:  23177158 ]
Gastroenterology. 2013 Jan;144(1):e26   [PMID:  23177160 ]

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