Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease

Abstract

Background: Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions. The aim of this study was to determine the diagnostic utility of non-invasive markers of fibrosis, validated in chronic viral hepatitis and alcoholic liver disease (FibroTest, FT), in patients with NAFLD.

Methods: 170 patients with suspected NAFLD were prospectively included in a reference center (Group 1), 97 in a multicenter study (Group 2) and 954 blood donors as controls. Fibrosis was assessed on a 5 stage histological scale validated by Kleiner et al from F0 = none, F1 = perisinusoidal or periportal, F2 = perisinusoidal and portal/periportal, F3 = bridging and F4 = cirrhosis. Histology and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) were assessed.

Results: In both groups FT has elevated and not different AUROCs for the diagnosis of advanced fibrosis (F2F3F4): 0.86 (95%CI 0.77-0.91) versus 0.75 (95%CI 0.61-0.83; P = 0.10), and for F3F4: 0.92 (95%CI 0.83-0.96) versus 0.81 (95%CI 0.64-0.91; P = 0.12) in Group 1 and Group 2 respectively. When the 2 groups were pooled together a FT cutoff of 0.30 had a 90% NPV for advanced fibrosis (Se 77%); a FT cutoff of 0.70 had a 73% PPV for advanced fibrosis (Sp 98%).

Conclusion: In patients with NAFLD, FibroTest, a simple and non-invasive quantitative estimate of liver fibrosis reliably predicts advanced fibrosis.

Figures

Figure 1

ROC curves of the FibroTest for the detection of advanced fibrosis in Group 1 and Group 2 (A), in the overall population (B), for bridging fibrosis or cirrhosis in Group 1 and Group 2 (C), and in the overall population (D). The diagonal line represents that achieved by chance alone (area under the curve 0.50); the ideal area under the curve is 1.00. Upper curve is Group1, lower curve is Group 2. There was no difference between the area under the ROC curves (AUROCs) for advanced fibrosis AUROC = 0.86 (95%CI 0.77–0.91) versus 0.75 (95%CI 0.61–0.83; P = 0.10), for bridging fibrosis or cirrhosis 0.92 (95%CI 0.83–0.96) versus 0.81 (95%CI 0.64–0.91; P = 0.12) in Group1 and Group 2 respectively. In the overall population the AUROCs for advanced fibrosis= 0.81 (95%CI 0.74–0.86) and for bridging fibrosis or cirrhosis = 0.88 (95%CI 0.82–0.92).

Figure 2

Relationship between fibrosis stage and the FibroTest. Notched box plots showing the relationship between the stage of fibrosis and FibroTest. The horizontal line inside each box represents the median and the width of each box the median ± 1.57 interquartile range/vn to assess 95% level of significance between group medians. Failure of the shaded boxes to overlap signifies statistical significance (P <0.05). The horizontal lines above and below each box encompass the interquartile range (from 25th to 75th percentile), and the vertical lines from the ends of the box encompass the adjacent values (upper: 75th percentile plus 1.5 times interquartile range, lower 25th percentile minus 1.5 times interquartile range). PS means perisinusoidal fibrosis; PP means periportal fibrosis. Spearman correlation coefficient between FibroTest and stage of fibrosis after exclusion of blood donors was = 0.44 (n = 267, P < 0.0001) and was = 0.47 (n = 1304, P < 0.0001) if blood donors were included in the analysis as subjects without fibrosis.