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. 2025 May 15;15(10):1253.
doi: 10.3390/diagnostics15101253.

Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Thierry Poynard  1   2   3   4   5 , Olivier Deckmyn  2 , Raluca Pais  1   3   4   5 , Judith Aron-Wisnewsky  1   3   4   5   6 , Valentina Peta  2 , Pierre Bedossa  7   8 , Frederic Charlotte  1   3 , Maharajah Ponnaiah  4 , Jean-Michel Siksik  3 , Laurent Genser  1   3   5 , Karine Clement  1   3   5 , Gilles Leanour  9 , Dominique Valla  7   10
Affiliations

Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Thierry Poynard et al. Diagnostics (Basel). .

Abstract

Background/Objectives: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis tests in patients with metabolic liver disease (MASLD). An unmet need is to reduce the uncertainty of biomarkers for the diagnosis of the early stage of clinically significant fibrosis (eF). This can be achieved if three essential but neglected STARD methods (3M) are used, which have a more sensitive histological score than the standard comparator (five-tiers), the weighted area under the characteristic curve (wAUROC) instead of the binary AUROC, and biopsy length. We applied 3M to FibroTest-T2D to demonstrate this reduction of uncertainty and constructed proxies predicting eF in large populations. Methods: For uncertainty, seven subsets were analyzed, four included biopsies (n = 1903), and to assess eF incidence, three MASLD-populations (n = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (n = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. Results: After BS (110 biopsies), reversal of eF was observed in 16/29 patients (84%) using seven-tier scores vs. 3/20 patients (47%) using five-tier scores (p = 0.005). When the biopsy length was above the median, FibroTest-T2D wAUROC was 0.90 (SD = 0.01), and the wAUROC was 0.88 (SD = 0.1) when the length was below the median (p < 0.001). For the first time, obesity was associated with eF before T2D (p < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (p < 0.0001). Conclusions: Validations of circulating biomarkers need to assess their uncertainty. FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance.

Keywords: Obuchowski measure; UK BioBank; biopsy length; early liver fibrosis; granularity; uncertainty.

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Conflict of interest statement

Thierry Poynard is the inventor of FibroTest and FibroTest-T2D and a fulltime employee and founder of BioPredictive, a spinoff of Sorbonne University that markets biomarkers. He is an emeritus professor at Sorbonne University. The tests’ patents belong to the public French organization “Assistance Publique Hôpitaux de Paris” and Sorbonne University. Olivier Deckmyn and Valentina Peta are full-time employees of BioPredictive. The other authors have no conflicts of interest. The RHU QUID-NASH project is funded by Agence Nationale de la Recherche Programme Investissements d’Avenir (grant ANR-17-T171105J-RHUS-0009 to D.V.). The RHU QUID NASH is implemented by Institut National de la Recherche Medicale, Paris Descartes University, Université Paris Cité, Centre National de la Recherche Scientifique, Centre de l’Energie Atomique, Servier, Biopredictive, and Assistance Publique-Hôpitaux de Paris.

Figures

Figure 1
Figure 1
Bariatric surgery performance for reducing fibrosis. (A) CRN-F1B was used as described in the resmetirom trial [7]. (B) Standard CRN was used [20]. (C) The FibroTest-T2D blood test was used [14,23]. The revised stage F0 includes no-fibrosis and the very low fibrosis substages F1, F1A, and F1C [7]. The three methods observed the absence of 100% (95% CI 91%-1; p < 0.001) of fibrosis progression.
Figure 2
Figure 2
CRN, FibroTest, and VCTE (y-axis) vs. area of fibrosis (x-axis) as the comparator reference (n = 1726). Increasing the granularity of the reference improved comparisons between non-invasive tests. (A) Biopsy CRN—five-tier stages vs. five-tier fibrosis area. (B) Biopsy CRN—seven-tier stages vs. seven-tier fibrosis area. (C) FibroTest—five-tier stages vs. five-tier fibrosis area. (D) FibroTest—seven-tier stages vs. seven-tier fibrosis area. (E) Seven-tier VCTE stages vs. five-tier fibrosis area. (F) Seven-tier VCTE stages vs. seven-tier fibrosis area.
Figure 2
Figure 2
CRN, FibroTest, and VCTE (y-axis) vs. area of fibrosis (x-axis) as the comparator reference (n = 1726). Increasing the granularity of the reference improved comparisons between non-invasive tests. (A) Biopsy CRN—five-tier stages vs. five-tier fibrosis area. (B) Biopsy CRN—seven-tier stages vs. seven-tier fibrosis area. (C) FibroTest—five-tier stages vs. five-tier fibrosis area. (D) FibroTest—seven-tier stages vs. seven-tier fibrosis area. (E) Seven-tier VCTE stages vs. five-tier fibrosis area. (F) Seven-tier VCTE stages vs. seven-tier fibrosis area.
Figure 3
Figure 3
Fibrosis progression rates (FPRs) to early fibrosis in US and French populations at risk of MASLD.
Figure 3
Figure 3
Fibrosis progression rates (FPRs) to early fibrosis in US and French populations at risk of MASLD.
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