Performance of this assay for F2-4 was determined by area under the receiver-operating characteristic curve (AUROC) using the DeLong method[20]. Values for AUROC were standardized relative to a uniform prevalence distribution, www.selleckchem.com/products/arq-197.html and an adjusted AUROC was calculated to account for spectrum bias, using the difference between the mean stage of advanced fibrosis minus the mean stage of nonadvanced fibrosis[21]. The FS modality provides a continuous regression index with a corresponding predicted individual fibrosis stage[22]. An FS index < 0.32 was used for stage F0-1. For two-stage predictive indices with FS for F0-1, F1-2, and F3-4, the midpoint index value was used as a threshold for assignment of stage for analysis. The TE cut-off values were chosen via AUROC analysis as the point at which sensitivity and specificity were maximized.
Recommended thresholds for TE in chronic HCV of > 7 kPa and > 12.5 kPa for F2 and F4, respectively, were also assessed[6]. For assessing the utility of combined FS and TE, prediction was based on a logistic-regression model containing both indices, as well as their pairwise interaction. The measure of agreement chosen was Cohen��s ��. Differences between continuous variables were assessed by Student��s t test, assuming unequal variance. All statistical analyses were performed using SAS? 9.2 (SAS Institute, Cary, NC). RESULTS Patient demographics Baseline biopsy (mean length 17 mm �� 9 mm) results were available from 2060 patients with chronic HCV. Patients were mostly men (58.1%) and caucasian (77.6%), with a mean age of 45.2 �� 11.
4 years and a prevalence of significant fibrosis of 18.3% (Table (Table11). Table 1 Baseline patient demographics n (%) Baseline FibroSURE performance Results for FS and biopsy were available in 2055 patients. For stages F2-4, FS had a sensitivity of 0.87, a specificity of 0.61, and an AUROC of 0.82 [95% confidence interval (CI) 0.80-0.84, Figure Figure1];1]; the corresponding adjusted AUROC relative to a uniform prevalence distribution was 0.84. For F4, sensitivity was 0.63, specificity was 0.85, and AUROC was 0.83 (95% CI 0.79-0.86). The misclassification rate for FS was 34% (n = 703/2055), and most of these patients (93%; n = 653) were false-positive F2-4 (Figure (Figure2).2). For biopsy specimens > 15 mm and F2-4 (46.0%; n = 948/2055), sensitivity was 0.86, specificity was 0.
61, and AUROC was 0.83 (95% CI 0.80-0.86). The FS misclassification rate, however, remained 34% in these patients with longer biopsy specimens. For biopsies > 15 mm and F4, sensitivity was 0.67, specificity was 0.84, and AUROC was Brefeldin_A 0.86 (95% CI 0.81-0.91). For moderate-severe necro-inflammatory activity of A2-3, sensitivity and specificity were both 0.66, and AUROC was 0.71 (95% CI 0.69-0.73). Figure 1 Baseline area-under-the-receiver-operating-curve analysis for stages F2-4 for FibroSURE and transient elastography.