Outcome prediction in metabolic dysfunction-associated steatotic liver disease using stain-free digital pathological assessment.

computer‐assisted cox model image processing metabolic dysfunction‐associated steatotic liver disease non‐alcoholic fatty liver disease pathology

Journal

Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857

Informations de publication

Date de publication:
07 Aug 2024
Historique:
revised: 23 07 2024
received: 07 05 2024
accepted: 27 07 2024
medline: 7 8 2024
pubmed: 7 8 2024
entrez: 7 8 2024
Statut: aheadofprint

Résumé

Computational quantification reduces observer-related variability in histological assessment of metabolic dysfunction-associated steatotic liver disease (MASLD). We undertook stain-free imaging using the SteatoSITE resource to generate tools directly predictive of clinical outcomes. Unstained liver biopsy sections (n = 452) were imaged using second-harmonic generation/two-photon excitation fluorescence (TPEF) microscopy, and all-cause mortality and hepatic decompensation indices constructed. The mortality index had greater predictive power for all-cause mortality (index >.14 vs. </=.14, HR 4.49, p = .003) than the non-alcoholic steatohepatitis-Clinical Research Network (NASH-CRN) (hazard ratio (HR) 3.41, 95% confidence intervals (CI) 1.43-8.15, p = .003) and qFibrosis stage (HR 3.07, 95% CI 1.30-7.26, p = .007). The decompensation index had greater predictive power for decompensation events (index >.31 vs. </=.31, HR 5.96, p < .001) than the NASH-CRN (HR 3.65, 95% CI 1.81-7.35, p < .001) or qFibrosis stage (HR 3.59, 95% CI 1.79-7.20, p < .001). These tools directly predict hard endpoints in MASLD, without relying on ordinal fibrosis scores as a surrogate, and demonstrate predictive value at least equivalent to traditional or computational ordinal fibrosis scores.

Identifiants

pubmed: 39109545
doi: 10.1111/liv.16062
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Innovate UK

Informations de copyright

© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.

Références

WHO Regional Office for Europe. SDR, chronic liver disease and cirrhosis, all ages, per 100 000. European health for all explorer 2021. Accessed May 31, 2022. https://gateway.euro.who.int/en/indicators/hfa_236‐1860‐sdr‐chronic‐liver‐disease‐and‐cirrhosis‐all‐ages‐per‐100‐000/
Lazarus JV, Mark HE, Villota‐Rivas M, et al. The global NAFLD policy review and preparedness index: are countries ready to address this silent public health challenge? J Hepatol. 2022;76:771‐780.
Brown GT, Kleiner DE. Histopathology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Metabolism. 2016;65:1080‐1086.
Sanyal AJ, Van Natta ML, Clark J, et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. New Engl J Med. 2021;385:1559‐1569.
Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of Resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497‐509.
Ratziu V, Friedman SL. Why do so many NASH trials fail? Gastroenterology. 2020;S0016‐5085(20):30680‐30686. doi:10.1053/j.gastro.2020.05.046
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313‐1321.
Angulo P, Kleiner DE, Dam‐Larsen S, et al. Liver fibrosis, but no other histologic features, associates with long‐term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389‐397.e10.
Vilar‐Gomez E, Calzadilla‐Bertot L, Wong VW‐S, et al. Fibrosis severity as a determinant of cause‐specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi‐National Cohort Study. Gastroenterology. 2018;155:443‐457.e17.
Jung ES, Lee K, Yu E, et al. Interobserver agreement on pathologic features of liver biopsy tissue in patients with nonalcoholic fatty liver disease. JPTM. 2016;50:190‐196.
Astbury S, Grove JI, Dorward DA, Guha IN, Fallowfield JA, Kendall TJ. Reliable computational quantification of liver fibrosis is compromised by inherent staining variation. J Pathol Clin Res. 2021;7:471‐481.
Ratziu V, Hompesch M, Petitjean M, et al. Artificial intelligence‐assisted digital pathology for non‐alcoholic steatohepatitis: current status and future directions. J Hepatol. 2024;80:335‐351.
Naoumov NV, Brees D, Loeffler J, et al. Digital pathology with artificial intelligence analyses provides greater insights into treatment‐induced fibrosis regression in NASH. J Hepatol. 2022;77:1399‐1409.
Kendall TJ, Jimenez‐Ramos M, Turner F, et al. An integrated gene‐to‐outcome multimodal database for metabolic dysfunction‐associated steatotic liver disease. Nat Med. 2023;29:2939‐2953.
Hagström H, Adams LA, Allen AM, et al. Administrative coding in electronic health care record‐based research of NAFLD: an expert panel consensus statement. Hepatology. 2021;74:474‐482.
Innes H, Morling JR, Buch S, Hamill V, Stickel F, Guha IN. Performance of routine risk scores for predicting cirrhosis‐related morbidity in the community. J Hepatol. 2022;77:365‐376.
Simon TG, Roelstraete B, Khalili H, Hagström H, Ludvigsson JF. Mortality in biopsy‐confirmed nonalcoholic fatty liver disease. Gut. 2021;70:1375‐1382.
Chang PE, Goh GBB, Leow WQ, Shen L, Lim KH, Tan CK. Second harmonic generation microscopy provides accurate automated staging of liver fibrosis in patients with non‐alcoholic fatty liver disease. PLoS ONE. 2018;13:e0199166.
Sanyal AJ, Jha P, Kleiner DE. Digital pathology for nonalcoholic steatohepatitis assessment. Nat Rev Gastroenterol Hepatol. 2023;21:57‐69. doi:10.1038/s41575-023-00843-7
Loomba R, Chalasani N. The hierarchical model of NAFLD: prognostic significance of histologic features in NASH. Gastroenterology. 2015;149:278‐281.
Brunt EM, Kleiner DE, Wilson LA, Sanyal AJ, Neuschwander‐Tetri BA. Nonalcoholic Steatohepatitis clinical research network. Improvements in histologic features and diagnosis associated with improvement in fibrosis in nonalcoholic Steatohepatitis: results from the nonalcoholic Steatohepatitis clinical research network treatment trials. Hepatology. 2019;70:522‐531.

Auteurs

Timothy J Kendall (TJ)

Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Edinburgh Pathology, University of Edinburgh, Edinburgh, UK.

Elaine Chng (E)

HistoIndex Pte Ltd, Singapore, Singapore.

Yayun Ren (Y)

HistoIndex Pte Ltd, Singapore, Singapore.

Dean Tai (D)

HistoIndex Pte Ltd, Singapore, Singapore.

Gideon Ho (G)

HistoIndex Pte Ltd, Singapore, Singapore.

Jonathan A Fallowfield (JA)

Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.

Classifications MeSH