Development of an accurate index for predicting outcomes of patients with acute liver failure

Anna Rutherford, Lindsay Y. King, Linda S. Hynan, Chetan Vedvyas, Wenyu Lin, William M. Lee, Raymond T. Chung

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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 log10 M30 and log10 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 log10 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; ClinicalTrials.gov, number NCT00518440.

Original languageEnglish (US)
Pages (from-to)1237-1243
Number of pages7
JournalGastroenterology
Volume143
Issue number5
DOIs
StatePublished - Nov 2012

Fingerprint

Acute Liver Failure
ROC Curve
Liver Transplantation
End Stage Liver Disease
Keratin-18
International Normalized Ratio
Coma
Bilirubin
Phosphorus
Biomarkers
Serum
Apoptosis
Patient Admission
Caspases
Ammonia
Lactic Acid
Creatinine
Body Mass Index
Necrosis
Logistic Models

Keywords

  • Cell Death Marker
  • Liver Disease Progression
  • Prognostic Factor
  • Risk Factor

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Development of an accurate index for predicting outcomes of patients with acute liver failure. / Rutherford, Anna; King, Lindsay Y.; Hynan, Linda S.; Vedvyas, Chetan; Lin, Wenyu; Lee, William M.; Chung, Raymond T.

In: Gastroenterology, Vol. 143, No. 5, 11.2012, p. 1237-1243.

Research output: Contribution to journalArticle

Rutherford, Anna ; King, Lindsay Y. ; Hynan, Linda S. ; Vedvyas, Chetan ; Lin, Wenyu ; Lee, William M. ; Chung, Raymond T. / Development of an accurate index for predicting outcomes of patients with acute liver failure. In: Gastroenterology. 2012 ; Vol. 143, No. 5. pp. 1237-1243.
@article{0f2ae6d5447e4c49aea58b02ec4f7f00,
title = "Development of an accurate index for predicting outcomes of patients with acute liver failure",
abstract = "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 log10 M30 and log10 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 log10 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; ClinicalTrials.gov, number NCT00518440.",
keywords = "Cell Death Marker, Liver Disease Progression, Prognostic Factor, Risk Factor",
author = "Anna Rutherford and King, {Lindsay Y.} and Hynan, {Linda S.} and Chetan Vedvyas and Wenyu Lin and Lee, {William M.} and Chung, {Raymond T.}",
year = "2012",
month = "11",
doi = "10.1053/j.gastro.2012.07.113",
language = "English (US)",
volume = "143",
pages = "1237--1243",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",

}

TY - JOUR

T1 - Development of an accurate index for predicting outcomes of patients with acute liver failure

AU - Rutherford, Anna

AU - King, Lindsay Y.

AU - Hynan, Linda S.

AU - Vedvyas, Chetan

AU - Lin, Wenyu

AU - Lee, William M.

AU - Chung, Raymond T.

PY - 2012/11

Y1 - 2012/11

N2 - 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 log10 M30 and log10 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 log10 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; ClinicalTrials.gov, number NCT00518440.

AB - 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 log10 M30 and log10 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 log10 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; ClinicalTrials.gov, number NCT00518440.

KW - Cell Death Marker

KW - Liver Disease Progression

KW - Prognostic Factor

KW - Risk Factor

UR - http://www.scopus.com/inward/record.url?scp=84868014401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868014401&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2012.07.113

DO - 10.1053/j.gastro.2012.07.113

M3 - Article

C2 - 22885329

AN - SCOPUS:84868014401

VL - 143

SP - 1237

EP - 1243

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 5

ER -