Diagnostic value of FibroTest with normal serum aminotransferases (2006)

Colletta et al et al.1 recently compared two noninvasive methods to detect fibrosis in 40 patients with chronic hepatitis C virus (HCV) and normal serum aminotransferase activity (ALT), and concluded that FibroScan (EchoSens, Paris, France) was superior to FibroTest (BioPredictive, Paris, France). They found perfect diagnostic values for FibroScan and for FibroTest (at the 0.31 cutoff) only 64% sensitivity and 31% specificity for the diagnosis of advanced fibrosis (F2F3F4). These poor results have not been observed for FibroTest in our experience2, 3 or others in studies using the professional service of Biopredictive, the sole company allowed to market FibroTest.4, 5 We analyzed 537 patients with chronic hepatitis C 129 with normal ALT and 408 with elevated ALT.3-6 There were no differences in area under the ROC curves (AUROCs) between patients with normal or elevated ALT (Table 1). The AUROC was 0.76, higher than the 43% accuracy observed by Colletta et al.1 We analyzed prospectively the specificity of FibroTest in 954 blood donors without liver biopsy, 917 with normal ALT; the security algorithms exclude 25 (3%) with high risk of false positive/negative. Among the remaining 892 subjects 877 (98.2%) have normal FibroTest and 15 (1.8%) had FibroTest between 0.31 and 0.48 and none above. These figures are very different than the 69% false positive of Colletta et al. (P < .00001).1 Four explanations are possible for these discrepancies. The first is the small number of patients. The second possible explanation could be an error in the calculation of FibroTest if the authors have not used the professional website (www.Biopredictive.com).The third possibility is the non exclusion of patients with high risk profile of false positive/negative3; i.e.,Gilbert syndrome, or acute inflammation with a high haptoglobin value. These high risk profiles would have been detected by the security algorithms on the website. The fourth possibility is the FibroTest threshold at 0.31 for F2F3F4 detection instead of 0.48 which is the recommended threshold. Finally we recently prospectively assessed the concordance between FibroTest and FibroScan in 70 consecutive subjects with baseline normal ALT: 60 patients (44 HCV, 5 hepatitis B, 11 others), and 10 apparently healthy volunteers. Fibroscan was not applicable in 3 subjects (Abdominal fat) and FibroTest in 5 (High risk profile). In the remaining 62 subjects the concordance was fair (kappa= 0.44, P < .001) with 78% (48/62) of concordance for stage F2F3F4 when using the 0.31 threshold and even better (82% (51/62) at the recommended threshold (0.48) (kappa= 0.45, P < .001). These concordance rates were similar to the 77% observed by Castera et al.4 The definition of “normal transaminases” can also be a source of heterogeneity between studies. Ideally, definitions of normal ALT values should be adjusted for sex and BMI to reduce artificial heterogeneity in blood donor selection and in hepatitis C clinical studies.7 In conclusion, we think the comparisons between noninvasive markers should be performed according to professional recommendations, respecting applicability reports to exclude high risk of false negative or false positive results and in populations with sufficient sample size. Thierry Poynard*, Mona Munteanu , Yen Ngo*, Mercedes Torres*, Yves Benhamou*, Dominique Thabut*, Vlad Ratziu*, * Service d“Hepato-Gastroenterologie, GH Pitie-Salpetriere, Pans, France, BioPredictive, Paris, France.