The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis

Abstract

Background: Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system.

Results: 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 - all significantly higher than the standard markers: gamma-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0-5%); 0.58 in grade 2 (6-32%); and 0.74 in grade 3-4 (33-100%). For the diagnosis of grade 2-4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively.

Conclusion: SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.

Figure 1

Flow chart of patients analyzed and included in the training and validation groups.

Figure 2

Relationship between ST, GGT and ALT and the grade of liver steatosis. A four grades scoring system was used to assess steatosis: S0 – no steatosis; S1 – mild, 1 to 5%; S2 – moderate, 6 to 32%; S3-S4 – marked or severe, 33 to 100%. Notched box plots showing the relationship (A) in the training group; (B) in validation group 1, HCV patients before treatment; (C) group 2, HCV sustained responders; (D) group 3, alcoholic liver disease; and (E) in controls, healthy volunteers fasting and non-fasting and non-fasting blood donors. The horizontal line inside each box represents the median and the width of each box the median ± 1.57 interquartile range/vn for assessing the 95% level of significance between group medians. Failure of the shaded boxes to overlap corresponds to statistical significance (P < 0.05). The horizontal lines above and below each box encompass the interquartile range (from 25^th to 75^th percentile), and the vertical lines from the ends of the box encompass the adjacent values (upper: 75^th percentile plus 1.5 times interquartile range, lower 25^th percentile minus 1.5 times interquartile range). In validation group 3, almost all patients had steatosis and group S0 and S1 were combined.

Figure 3

Relationship between ST, and the grade of liver steatosis in the integrated database combining controls, training group and validation groups. Failure of the shaded boxes to overlap indicates statistical significance between medians (P < 0.05). There was a significant difference between all grades by the Tukey-Kramer multiple comparison test for all pairwise differences between means (P < 0.05). For GGT and ALT, there was no significant difference between S0 and S1 and between S2 and S3. For ALT, there was also no significant difference between S0 and S2, S1 and S2.