Variability of the area under the receiver operating characteristic curves in the diagnostic evaluation of liver fibrosis markers: impact of biopsy length and fragmentation.
BACKGROUND
The area under the receiver operating characteristic (ROC) curve is widely used as an estimate of the diagnostic value for fibrosis markers. Biopsy length and fragmentation are known as risk factors of false positive or false negative of biopsy but their quantitative impact on area under the receiver operating characteristic curve variability has not been assessed.


OBJECTIVE
To assess these relationships to better compare the fibrosis markers.


METHODS
The area under the ROC curves of FibroTest for the diagnosis of fibrosis was estimated in patients with chronic hepatitis C using an integrated database including 1312 patients with FibroTest and biopsy. To take into account the biopsy length, we used two adjustment factors: one in which an observed area under the ROC curve could be adjusted according to the relative area under the receiver operating characteristic curve of a biopsy of a given length vs. the entire liver and one taking into account the prevalence of each fibrosis stage defining advanced and non-advanced fibrosis.


RESULTS
The mean biopsy length was smaller for cirrhosis (F4, 16 mm) vs. F3, (18 mm, P=0.01) and F0 (19 mm, P=0.01). The mean number of fragments was higher for cirrhosis (F4=4.1 fragments) vs. all the other stages (F0=1.9, F1=1.9, F2=1.9, F3=2.3; P<0.001 vs. F4). The FibroTest area under the ROC curves for the diagnosis of advanced fibrosis, adjusted for stages' prevalence, ranged from 0.80 to 0.98 depending on biopsy length and fragmentation, respectively.


CONCLUSIONS
The comparison of the area under the ROC curves of fibrosis markers should take into account the biopsy length and fragmentation.
Poynard
T
T
APHP Groupe Hospitalier Pitié-Salpêtrière, Paris, France. tpoynard@teaser.fr
Halfon
P
P
Castera
L
L
Charlotte
F
F
Le Bail
B
B
Munteanu
M
M
Messous
D
D
Ratziu
V
V
Benhamou
Y
Y
Bourlière
M
M
De Ledinghen
V
V
D019540:Area Under Curve; D015415:Biomarkers; D001707:Biopsy, Needle / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
D015415:Biomarkers