Concordance in a world without a gold standard: a new non-invasive methodology for improving accuracy of fibrosis markers.
BACKGROUND
Assessing liver fibrosis is traditionally performed by biopsy, an imperfect gold standard. Non-invasive techniques, liver stiffness measurements (LSM) and biomarkers [FibroTest(R) (FT)], are widely used in countries where they are available. The aim was to identify factors associated with LSM accuracy using FT as a non-invasive endpoint and vice versa.


METHODS
The proof of concept was taken using the manufacturers recommendations for excluding patients at high risk of false negative/positive. The hypothesis was that the concordance between LSM and FT, would be improved by excluding high-risk patients. Thereafter, the impact of potential variability factors was assessed by the same methods. Liver biopsy and independent endpoints were used to validate the results.


RESULTS
Applying manufacturers' recommendations in 2,004 patients increased the strength of concordance between LSM and FT (P<0.00001). Among the 1,338 patients satisfying recommendations, the methodology identified a significant LSM operator effect (P = 0.001) and the following variability factors (all P<0.01), related to LSM: male gender, older age, and NAFLD as a cause of liver disease. Biopsy confirmed in 391 patients these results.


CONCLUSIONS
This study has validated the concept of using the strength of concordance between non-invasive estimates of liver fibrosis for the identification of factors associated with variability and precautions of use.
Poynard
Thierry
T
APHP Groupe Hospitalier Pitié-Salpêtrière, Université Paris VI, CNRS UMR, Paris, France. tpoynard@teaser.fr
Ingiliz
Patrick
P
Elkrief
Laure
L
Munteanu
Mona
M
Lebray
Pascal
P
Morra
Rachel
R
Messous
Djamila
D
Bismut
Francoise Imbert
FI
Roulot
Dominique
D
Benhamou
Yves
Y
Thabut
Dominique
D
Ratziu
Vlad
V
D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results
D015415:Biomarkers