Background & Aims
Progressive fibrosis is a major cause of morbidity and mortality in chronic liver
disease. To replace liver biopsy for disease staging, multiple serum markers are under
evaluation with multiparametric panels yielding the most promising results. The Enhanced
Liver Fibrosis (ELF) score is an ECM marker set consisting of tissue inhibitor of
metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP)
and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic
liver disease.
Methods
The ELF score was measured in 400 healthy controls and 79 chronic hepatitis C patients
using an ADVIA Centaur automated system. The ELF score was calculated using the published
algorithm combining TIMP-1, PIIINP and HA values. Patients’ fibrosis stage was defined
histologically. ROC analyses were performed to study marker validity. Reference values
and influence factors for the ELF score were validated.
Results
ELF score reference values ranged from 6.7 to 9.8 and were significantly higher for
men vs. women (7.0–9.9 vs. 6.6–9.3, respectively). Afternoon values were slightly higher than morning values
(6.7–9.9 vs. 6.6–9.5, respectively). Age was a notable influence factor. We identified three cut-off
values: 7.7 for a high sensitivity exclusion of fibrosis, 9.8 for a high specificity
identification of fibrosis (sensitivity 69%, specificity 98% for moderate fibrosis),
and 11.3 to discriminate cirrhosis (sensitivity 83%, specificity 97%). ELF score validity
was superior to the results of the single tests.
Conclusions
The ELF score can predict moderate fibrosis and cirrhosis. However, influence factors
such as gender and age need to be taken into account.
Abbreviations:
ELF (enhanced liver fibrosis), ECM (extracellular matrix), TIMP-1 (tissue inhibitor of metalloproteinases 1), PIIINP (amino-terminal propeptide of type III procollagen), HA (hyaluronic acid), HSC (hepatic stellate cells), CHC (chronic hepatitis C), HCV (hepatitis C virus), ALT (alanine aminotransferase), AST (aspartate aminotransferase), AP (alkaline phosphatase), γGT (gamma-glutamyltransferase), CI (confidence interval), Kcal (kilocalories), ROC (receiver operating characteristics), AUC (area under the curve.)Keywords
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Article info
Publication history
Published online: March 25, 2013
Accepted:
March 13,
2013
Received in revised form:
February 9,
2013
Received:
September 11,
2012
Identification
Copyright
© 2013 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
