FibroScan and FibroTest to assess liver fibrosis in HCV with normal aminotransferases^†

We read with interest the article by Colletta et al. on the utility of FibroScan and FibroTest for the noninvasive detection of fibrosis progression in hepatitis C virus (HCV) carriers with normal aminotransferases.1 Although we share the authors' view that these noninvasive methods could become an alternative to liver biopsy in this setting, we would nevertheless like to raise several methodological concerns regarding this study.

First, as noted in the accompanying editorial,2 the findings of Colletta et al. regarding the remarkable capability of FibroScan to distinguish the full spectrum of histopathological fibrosis stage in patients who have persistently normal alanine aminotransferase (ALT) levels are in stark contrast to those published thus far, including the findings reported by our own group.3, 4 As with any new diagnostic test—and, given their limited number of patients—the authors should be cautious when interpreting their data regarding the perfect agreement between FibroScan and liver biopsy. Indeed, the diagnostic performance of FibroScan reported in this study is quite surprising, with sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%. A critical issue is the choice of the cutoff value for identifying patients with significant fibrosis (i.e., METAVIR F ≥2), because two cutoffs have been reported to date: 7.1 kPa3 and 8.7 kPa.4 However, the authors did not provide any justification for the choice of their cutoff. Hence, choosing the cutoff we proposed, the results reported by Colletta et al. might have been fairly different with lower diagnostic performances (sensitivity 100%, specificity 46%, diagnostic accuracy 46%, positive predictive value 50%, negative predictive value 100%). Indeed, 12 (46%) of the 26 patients without significant fibrosis would have been misclassified.

Second, no information is provided by the authors regarding the proportion of patients in whom liver elasticity measurements could not be obtained. This proportion is close to 5% in our experience in more than 2,000 examinations,5 implying a FibroScan failure could be expected in at least one or two patients.

Third, the authors should be cautious when asserting that FibroScan has a far better correlation with liver biopsy than FibroTest given the rather poor performances of FibroTest in their study with a surprisingly high false positive rate, in contrast with previously published studies showing high specificity in blood donors.6

One way to avoid limitations of both methods is to use the algorithm combining FibroScan and FibroTest, recently proposed by us in HCV patients with elevated ALT levels.3 Accordingly, we assessed prospectively the concordance between FibroScan and FibroTest in 100 consecutive HCV patients with normal ALT levels. Liver elasticity measurements could not be obtained in 3 patients. In the remaining 97 patients (34 male, 63 female; mean age 55 ± 14 years), the median FibroScan value was 4.9 kPa (range 2.6–13.3). Concordance between FibroScan and FibroTest for significant fibrosis (METAVIR F2-F3-F4) was 67%, using either a cutoff of 7.1 kPa or 8.7 kPa (Table 1).

In conclusion, we believe combining FibroScan and FibroTest as a first-line noninvasive assessment of liver fibrosis might prove particularly useful in the setting of HCV carriers with normal ALT levels and should be further evaluated.