Reply (2009)

We appreciate the thoughtful comments by Alisi and colleagues, who highlighted the similar accuracy of transient elastography to detect advanced fibrosis in both adults and children with nonalcoholic fatty liver disease (NAFLD). There are a number of unresolved issues in the use of transient elastography in NAFLD. First, as shown in our study, measurements could not be made in some obese patients.1 A lower success rate was also observed in obese patients with other liver diseases such as viral hepatitis and cholestatic liver disease.2 The mechanical shear wave and Doppler signal may not transmit well to the liver parenchyma in patients with thick subcutaneous fat. Further development, including the use of the new probe for obese patients, is encouraged.3 Second, although transient elastography has excellent negative predictive value in excluding advanced fibrosis and cirrhosis in patients with NAFLD, the positive predictive value in diagnosing advanced disease remains modest. Alisi and colleagues rightly commented that combination of different noninvasive tests may further improve the diagnostic accuracy and reduce the need for liver biopsy. Based on the analysis of our cohort as well as another study from the U.S. National Institutes of Health NASH Clinical Research Network, the FIB-4 index has highest accuracy for fibrosis in NAFLD among all noninvasive markers.1, 4 To test the potential of combining transient elastography and biomarkers in NAFLD, we reanalyzed our data using the FIB-4 index. Among 148 patients with liver stiffness measurement (LSM) <7.9 kPa, only five with ≥F3 disease were incorrectly classified. When the FIB-4 index was applied to these patients, 126 had FIB-4 index below the lower cutoff value of 1.30. Using both tests, three patients with ≥F3 disease were incorrectly classified. The overall negative predictive value of the combined tests was 97.6% (95% confidence interval, 95.0%-100%). Among 58 patients with LSM ≥9.6 kPa, 13 had FIB-4 index above the higher cutoff value of 2.67 (Fig. 1). Two patients without advanced fibrosis were misclassified. The overall positive predictive value of the combined tests was 84.6% (95% confidence interval, 65.0%-100%). In comparison, the positive and negative predictive values of the original model using transient elastography alone were 72.4% and 96.6%, respectively.1 Prediction of advanced fibrosis in patients with NAFLD using transient elastography and the FIB-4 index. Because the addition of FIB-4 could not significantly improve the performance of LSM to exclude advanced fibrosis, its major role is probably a confirmatory test for advanced fibrosis as suggested by transient elastography. If liver biopsy was performed in all patients with LSM >7.9 kPa, 98 (39.8%) patients of the entire cohort required the procedure. If liver biopsy was performed only in patients with discordant transient elastography and FIB-4 index when LSM is >9.6 kPa, 85 (34.6%) patients required the procedure (Fig. 1). Other new noninvasive tests, such as Fibrometer, could be useful in combination with LSM and have to be evaluated in these patients.5 In conclusion, transient elastography alone has good negative predictive value in excluding advanced fibrosis and cirrhosis in patients NAFLD. The main role of combined noninvasive tests would be to increase the positive predictive value in diagnosing advanced disease. This can be achieved when more specific biomarkers of liver fibrosis are identified in the future. Vincent Wai-Sun Wong* , Julien Vergniol , Henry Lik-Yuen Chan* , Victor de Lédinghen §, * Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China, Centre d'Investigation de la Fibrose Hépatique, Centre Hospitalier Universitaire (CHU) de Bordeaux, Hôpital Haut-Lévêque, France, § Institut National de la Santé et de la, Recherche Médicale U889, Université Victor Segalen, Bordeaux, France.