Abstract
Introduction Noninvasive methods for assessing liver fibrosis are increasingly important for early detection of advanced liver fibrosis (ALF), particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the overall diagnostic ability and efficiency (ODAE) of noninvasive diagnostic strategies incorporating imaging tests and to identify optimal test combinations for early ALF detection. Methods We conducted a simulation of 10,000 MASLD patients, assuming an ALF prevalence of 15%. Two diagnostic strategies were evaluated. Strategy one (two-step): patients positive on the Fibrosis-4 (Fib-4) index (cutoff ≥1.3) underwent magnetic resonance elastography (MRE), vibration-controlled transient elastography (VCTE), or shear wave elastography (SWE). Strategy two (three-step): Fib-4-positive patients underwent additional serum fibrosis marker testing - enhanced liver fibrosis score, Mac-2-binding protein glycosylation isomer, or type IV collagen 7S - followed by imaging if positive. Diagnostic performance, including net sensitivity, specificity, predictive values, and accuracy, was estimated using decision tree analysis based on published parameters. Results Fib-4 identified 5,742 positive cases. Strategy one achieved high accuracy (0.90-0.93); combining Fib-4 with MRE or SWE as a secondary test demonstrated good and comparable ODAE. Strategy two further improved positive predictive value and reduced false positives compared with strategy one. Conclusions Combining Fib-4 with MRE or SWE provides comparable and efficient diagnostic performance for early detection of ALF. Adding serum fibrosis markers as an intermediate step may further reduce false positives and enhance diagnostic accuracy.