Background & Aims
Predicting the probability of patients with acute liver failure (ALF) to recover spontaneously
is of major clinical importance. As apoptotic and necrotic cell death are crucial
in the pathogenesis of ALF, we determined whether selected cell-death markers predict
outcome of patients with ALF and/or discriminate between etiologies.
Methods
In a prospective study (11/2006–06/2009), 68 ALF patients were recruited consecutively.
Data were collected over four weeks or until discharge, death or LTx, including CK18/M65
and M30 ELISA and glutathione S-transferase, subtype α. Data at date of admission and at the date of peak levels
of M65 were individually analyzed and correlated with the patients’ prognosis and
etiology.
Results
The predictive sensitivity of total serum M65 for lethal outcome was comparable to
the Model for End-Stage Liver Disease (MELD) score at time of admission and at its
peak value. In contrast, serum bilirubin levels had no prognostic value, neither at
admission nor at later time points. In order to accurately predict the clinical prognosis
of ALF patients, we tested a modified MELD score where CK18 M65 substituted bilirubin.
This CK18/M65-based MELD score significantly better predicted the prognosis of ALF
patients compared with the current MELD score or KCC. A combination of tested parameters
contributed to improved discrimination of ALF etiologies by applying cell death and
established laboratory parameters.
Conclusions
The CK18 M65-based MELD score has superior sensitivity and specifically predicts survival
of ALF patients. Further prospective clinical studies could validate its potential
role to predict requirement of LTx in ALF patients.
Abbreviations:
ALF (acute liver failure), LTx (liver transplantation), CK18 (cytokeratin 18), KCC (Kings College Criteria), MELD (Model for End-Stage Liver Disease), ELISA (enzyme-linked immunosorbent assay), GST-α (glutathione S-transferase, subtype α), CHF (congestive heart failure), ALI (acute liver injury), SR (spontaneous remission), NSR (non-spontaneous remission), AST (aspartate aminotransferase), ALT (alanine aminotransferase), AP (alcalic phosphatase), γ-GT (gamma-glutathione), INR (international normalized ratio), AUC (area under the curve), M-MELD (M65 modified Model for End-Stage Liver Disease), AAP (acetaminophene poisoning), NAAP (non-acetaminophen poisoning), GLDH (glutamate dehydrogenase), HBV (hepatitis B virus)Keywords
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Article info
Publication history
Published online: July 01, 2010
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
