Noninvasive Test Shows Accuracy for Detecting Advanced Liver Fibrosis in MASH

A newly validated noninvasive scoring tool has shown superior performance in identifying metabolic dysfunction–associated steatohepatitis (MASH) patients with advanced liver fibrosis, offering a potential step forward in reducing reliance on biopsy and improving risk stratification in the most common chronic liver disease worldwide.1

The findings, published by researchers in Spain in Biomarker Research, confirmed that the BMP8A Fibrosis Score (BFS) more accurately classifies patients with severe fibrosis than several widely used diagnostic algorithms while eliminating the grey-zone results that often complicate clinical decision-making.

Additional validation in broader populations, inter-laboratory reproducibility studies, and commercial assay availability will be necessary before widespread adoption. | Image credit: Connect world - stock.adobe.com

Although liver biopsy remains the gold standard for staging fibrosis, it is invasive, costly, and impractical to perform routinely. Existing noninvasive scoring systems, such as the Fibrosis-4 (FIB-4) Index, NAFLD Fibrosis Score (NFS), Hepamet Fibrosis Score (HFS), and AST-to-Platelet Ratio Index (APRI), are widely used but have limitations, explained the researchers. Many patients fall into intermediate “grey zones,” where results are inconclusive and further testing is required. Variability in sensitivity and specificity across clinical settings further limits their reliability.

Researchers previously identified circulating bone morphogenetic protein 8A (BMP8A) as a promising biomarker after observing that serum levels rise progressively with fibrosis severity.2 Building on these earlier findings, the team developed the BFS, which integrates BMP8A concentration with patient age and platelet count. In its initial derivation study, BFS showed encouraging accuracy in distinguishing advanced fibrosis in patients with biopsy-confirmed MASH.

To validate the score in an independent population, investigators analyzed serum BMP8A levels in 302 patients with MASH across 7 university hospitals in Spain. Of these, 171 had no or mild fibrosis (F0-F2), and 131 had advanced fibrosis (F3–F4). Serum BMP8A concentrations were significantly higher in patients with advanced fibrosis, averaging 339.6 pg/mL compared with 230.5 pg/mL in earlier-stage disease, with a clear stepwise increase across fibrosis stages.

Diagnostic accuracy was assessed using area under the receiver operating characteristic (AUROC) curves and compared directly against other noninvasive scores. BMP8A alone had an AUROC of 0.669, while the composite BFS achieved 0.750, outperforming FIB-4 (0.747), HFS (0.723), APRI (0.706), and NFS (0.650). Although not dramatically higher, BFS delivered the strongest overall accuracy and, crucially, provided a single cutoff value of 0.46. Unlike competing scores that rely on dual thresholds and create indeterminate zones, BFS eliminates ambiguous results.

Using that cutoff, BFS correctly classified 70.9% of patients with advanced fibrosis, with a specificity of 80.7% and a positive predictive value (PPV) of 69.7%. Its negative predictive value (NPV) of 71.5% and likelihood ratio profile (LR+ 3.0; LR– 0.5) supported both ruling in and ruling out advanced disease. In contrast, FIB-4 at its commonly used ≥2.67 threshold correctly identified only 63.6% of advanced cases and misclassified a substantial proportion due to false negatives and indeterminate outputs. HFS and APRI performed similarly or worse, especially when restricted to higher cutoffs, and NFS showed the lowest diagnostic utility in this cohort.

By eliminating grey-zone classifications, BFS categorized 63.9% of the cohort as F0–F2 and 36.1% as F3–F4, providing a decisive result in every case. The authors noted that this feature may be particularly important in clinical trial screening, where rapid and reliable fibrosis stratification is required without exposing patients to unnecessary biopsy. The group noted that the multicenter design of their study strengthens generalizability, reflecting diverse patient populations and real-world variability across laboratories and hospitals.

However, the researchers acknowledged limitations of their findings. Because BFS requires ELISA-based measurement of serum BMP8A, it may be costlier and less accessible than scores derived exclusively from routine laboratory data.

“This drawback parallels other specialized biomarkers, such as MACK3, which improve accuracy but require additional assays, sometimes not available in commercial laboratories, as is the case with BFS,” wrote the researchers.

They emphasized that additional validation in broader populations, inter-laboratory reproducibility studies, and commercial assay availability will be necessary before widespread adoption. They also noted that BFS, like other biomarkers, should be interpreted alongside imaging tools such as elastography, which continue to play an expanding role in fibrosis assessment.

References

1. Isaza SC, Fernández-García CE, Rojo D, et al. Validation of BMP8A fibrosis score to identify patients with metabolic dysfunction-associated steatohepatitis with advanced liver fibrosis. Biomark Res. Published online November 19, 2025. doi:10.1186/s40364-025-00862-3

2. Marañón P, Isaza SC, Fernández-García CE, Rey E, Gallego-Durán R, Montero- Vallejo R, et al. Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis. Biomark Res. 2023;11(1):46. doi:10.1186/s40364-023-00489-2