Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
<b>Background/Objectives:</b> 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 biomarker...
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MDPI AG
2025-05-01
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| author | Thierry Poynard Olivier Deckmyn Raluca Pais Judith Aron-Wisnewsky Valentina Peta Pierre Bedossa Frederic Charlotte Maharajah Ponnaiah Jean-Michel Siksik Laurent Genser Karine Clement Gilles Leanour Dominique Valla |
| author_facet | Thierry Poynard Olivier Deckmyn Raluca Pais Judith Aron-Wisnewsky Valentina Peta Pierre Bedossa Frederic Charlotte Maharajah Ponnaiah Jean-Michel Siksik Laurent Genser Karine Clement Gilles Leanour Dominique Valla |
| author_sort | Thierry Poynard |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> 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. <b>Methods:</b> For uncertainty, seven subsets were analyzed, four included biopsies (<i>n</i> = 1903), and to assess eF incidence, three MASLD-populations (<i>n</i> = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (<i>n</i> = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. <b>Results:</b> 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 (<i>p</i> = 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 (<i>p</i> < 0.001). For the first time, obesity was associated with eF before T2D (<i>p</i> < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (<i>p</i> < 0.0001). <b>Conclusions:</b> 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. |
| format | Article |
| id | doaj-art-cd8c773758854d84a67da1fd7f238e4e |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-cd8c773758854d84a67da1fd7f238e4e2025-08-20T01:56:16ZengMDPI AGDiagnostics2075-44182025-05-011510125310.3390/diagnostics15101253Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)Thierry Poynard0Olivier Deckmyn1Raluca Pais2Judith Aron-Wisnewsky3Valentina Peta4Pierre Bedossa5Frederic Charlotte6Maharajah Ponnaiah7Jean-Michel Siksik8Laurent Genser9Karine Clement10Gilles Leanour11Dominique Valla12Medical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceBioPredictive, 75007 Paris, FranceMedical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceMedical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceBioPredictive, 75007 Paris, FranceUMR1149 (CRI), Inserm, Université Paris Cité, 75018 Paris, FranceMedical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceInstitut National de la Santé et de la Recherche Médicale, 75013 Paris, FranceAssistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, FranceMedical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceMedical Faculty Pitié Salpêtrière, Sorbonne University, 75005 Paris, FranceCNRS UMR8507, Laboratoire Génie Électrique et Électronique de Paris (GeePs), Sorbonne Université, 75252 Paris, FranceUMR1149 (CRI), Inserm, Université Paris Cité, 75018 Paris, France<b>Background/Objectives:</b> 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. <b>Methods:</b> For uncertainty, seven subsets were analyzed, four included biopsies (<i>n</i> = 1903), and to assess eF incidence, three MASLD-populations (<i>n</i> = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (<i>n</i> = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. <b>Results:</b> 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 (<i>p</i> = 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 (<i>p</i> < 0.001). For the first time, obesity was associated with eF before T2D (<i>p</i> < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (<i>p</i> < 0.0001). <b>Conclusions:</b> 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.https://www.mdpi.com/2075-4418/15/10/1253uncertaintyObuchowski measureearly liver fibrosisgranularityUK BioBankbiopsy length |
| spellingShingle | Thierry Poynard Olivier Deckmyn Raluca Pais Judith Aron-Wisnewsky Valentina Peta Pierre Bedossa Frederic Charlotte Maharajah Ponnaiah Jean-Michel Siksik Laurent Genser Karine Clement Gilles Leanour Dominique Valla Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Diagnostics uncertainty Obuchowski measure early liver fibrosis granularity UK BioBank biopsy length |
| title | Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) |
| title_full | Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) |
| title_fullStr | Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) |
| title_full_unstemmed | Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) |
| title_short | Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) |
| title_sort | three neglected stard criteria reduce the uncertainty of the liver fibrosis biomarker fibrotest t2d in metabolic dysfunction associated steatotic liver disease masld |
| topic | uncertainty Obuchowski measure early liver fibrosis granularity UK BioBank biopsy length |
| url | https://www.mdpi.com/2075-4418/15/10/1253 |
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