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The reliable diagnosis rate of diagnostic tests is provided by their intervals with acceptable accuracy (e.g. ≥90%) where a liver biopsy can be avoided.To evaluate the overall accuracy and improve the reliable diagnosis rates of blood tests for significant liver fibrosis.Five blood tests were compared with Metavir fibrosis (F) staging in 1056 patients with chronic hepatitis C.Area under the receiver operating characteristics (F0-1 vs. F2-4) were: FibroMeter: 0.853, Fibrotest: 0.811, Fib-4: 0.799, aspartate aminotransferase to platelet ratio index (APRI): 0.786 and Hepascore: 0.784 (P<10−3 between tests). The reliable diagnosis rates based on two traditional intervals defined by thresholds ≥90% of negative predictive values (NPV) and positive predictive values (PPV), diagnosing F0/1 and F2/3/4, respectively, were: FibroMeter: 43.5%, APRI: 19.6%, Fibrotest: 17.1%, Hepascore: 3.9%, Fib-4: 1.7% (P<10−3). By dividing the indeterminate interval by the diagnostic cut-off, two new intervals could be diagnosed reliably: F1/2 and F1/2/3. Accordingly, the reliable diagnosis rate was increased, e.g. FibroMeter: 75.5% (accuracy: 89.5%) with three intervals (F0/1, F1/2, F2/3/4). It was possible to further increase this rate by using the more exportable 90% sensitivity/specificity thresholds, e.g. FibroMeter: 90.2% (accuracy: 86.4%). By using the four intervals, the reliable diagnosis rate was 100% (accuracy: 89.5% with predictive value (PV) and 87.5% with sensitivity/specificity).Reliable diagnosis is a diagnostic index devoted to clinical practice. Its rate can be increased by creating new intervals between diagnostic cut-off and 90% PVs or sensitivity/specificity thresholds. This increased the overall accuracy from 78.1 to 89.5% and reduced the need for a liver biopsy from 56.5 to 0% with the most accurate test.