Clinical interpretation of Fibroscan® results: a real challenge

Ultrasonographical elastometry by Fibroscan is thought to be a device that non-invasively and accurately evaluates the level of liver fibrosis (1). However, many other conditions could influence the liver stiffness level: acute hepatitis or flare-up (2, 3), cholestasis (4), steatosis (5) or cardiac failure (6). Another parameter to consider for the interpretation of Fibroscan results is the validity of liver stiffness evaluation (LSE). Indeed, a single result may be erroneous because of various conditions (probe position or inclination, respiratory movement, etc.). Thus, physicians have to determine the LSE validity, i.e. whether the LSE result corresponds to the ‘real’ liver stiffness. The manufacturer recommends obtaining 10 valid ‘shots’ (pulses), with a success rate Z60% and an interquartile range/median ratio (IQR/M) 30% before considering an LSE as valid (1). However, despite their wide use, the relevance of these criteria remains poorly evaluated. Finally, two possible causes of discrepancy between elastometry and histological fibrosis stage must be considered: invalid LSE and conditions that modify liver stiffness irrespective of the level of fibrosis. Lucidarme et al. (7) have recently evaluated the cause of discrepancies between Fibroscan results and histological fibrosis stages in 254 patients with chronic hepatitis C. In this study, all patients had LSE with at least 10 valid shots. The independent predictors of discrepancies were the IQR/M ratio and severe fibrosis (Metavir F3–4), but the success rate was not predictive. In this issue of Liver International, Myers et al. (8) evaluated discrepancies between Fibroscan and histological fibrosis stage in 251 patients with various causes of chronic liver disease. They confirm the key role of IQR/M and the absence of influence of LSE success rate on discrepancies. The results also showed that none of the three validity criteria recommended by the manufacturer was associated with a significant improvement of Fibroscan accuracy. It should be noted that the combination of the three factors was not evaluated in this study. Nevertheless, all these data suggest that the manufacturer’s recommendations were arbitrary and may need revision. At present, the minimal number of valid shots for LSE remains unknown. In their study, Myers and colleagues showed no significant difference of AUROC between LSE with o 10 valid shots and those with Z10. Recently, Kettaneh et al. (9) showed that AUROC of Fibroscan was not significantly different with 3, 5 or 10 valid shots. Rather than the number of valid shots, the Lucidarme and Myers studies suggest that the more important criterion for LSE validity is the ratio IQR/M, i.e. the dispersion among the results of valid LSE shots. In these studies, the best calculated cut-offs of IQR/M were, respectively, 0.21 and 0.17. With another methodology, our team has shown that IQR/Mo 0.25 was required for a reproducible LSE result (10). Thus, available data suggest that the key factor for LSE validity is to obtain an IQR/M around 0.20, whatever the LSE success rate. Because it is an easy-to-perform and rapid procedure, we suggest that LSE should include 10 valid shots (11). In case of difficult LSE, especially in obese patients (12), five valid shots may be sufficient, provided IQR/M is 0.20. However, application of these new criteria will lead to a high rate of LSE exclusions: 47% of patients had an LSE with IQR/M Z0.17 in the Myers study, and 46.5% had IQR/M Z0.21 in the Lucidarme study. Finally, the independent role of the dispersion of valid shots for LSE validity remains to be further confirmed in larger independent series. These studies will have to test the effect of dispersion by using IQR/M but also other indices, to evaluate the influence of each independent factor identified (e.g., with the adjusted R of the multivariate analysis, or equivalent), and finally to precisely define the criteria of LSE validity. Such criteria are especially useful for longitudinal studies evaluating the natural history of liver fibrosis or anti-fibrotic agents. It should be noted that criteria for LSE validity have not been applied to diagnostic studies evaluating the accuracy of Fibroscan because such studies must be conducted on an intention-to-diagnose basis according to the STARD recommendations (13). Myers and colleagues also identified BMI, serum ALT and fibrosis stage as independent predictors of discrepancies between the Fibroscan result and the histological fibrosis stage. Such findings are interesting because they identify the situations where Fibroscan results must be interpreted with caution. However, the study of the discrepancies between Fibroscan and liver biopsy results needs to address several methodological challenges. The first issue is the definition of discrepancy. In the Lucidarme and Myers studies, Fibroscan results were categorized into fibrosis stages according to diagnostic cut-offs, and then compared with histological fibrosis stages. However, diagnostic cut-offs are provided by statistical methods aimed at a binary diagnosis like significant fibrosis or cirrhosis. The combination of these different diagnostic cut-offs may decrease the statistical validity because it accumulates the diagnostic errors of