Agile scores in MASLD and ALD: External validation and their utility in clinical algorithms

Background & Aims - Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We indep...

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Main Authors: Papatheodoridi, Margarita (Author) , De Ledinghen, Victor (Author) , Lupsor-Platon, Monica (Author) , Bronte, Fabrizio (Author) , Boursier, Jerome (Author) , Elshaarawy, Omar (Author) , Marra, Fabio (Author) , Thiele, Maja (Author) , Markakis, Georgios (Author) , Payance, Audrey (Author) , Brodkin, Edgar (Author) , Castera, Laurent (Author) , Papatheodoridis, George (Author) , Krag, Aleksander (Author) , Arena, Umberto (Author) , Mueller, Sebastian (Author) , Cales, Paul (Author) , Calvaruso, Vincenza (Author) , Delamarre, Adele (Author) , Pinzani, Massimo (Author) , Tsochatzis, Emmanuel A. (Author)
Format: Article (Journal)
Language:English
Published: 23 May 2024
In: Journal of hepatology
Year: 2024, Volume: 81, Issue: 4, Pages: 590-599
ISSN:1600-0641
DOI:10.1016/j.jhep.2024.05.021
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jhep.2024.05.021
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0168827824003568
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Author Notes:Margarita Papatheodoridi, Victor De Ledinghen, Monica Lupsor-Platon, Fabrizio Bronte, Jerome Boursier, Omar Elshaarawy, Fabio Marra, Maja Thiele, Georgios Markakis, Audrey Payance, Edgar Brodkin, Laurent Castera, George Papatheodoridis, Aleksander Krag, Umberto Arena, Sebastian Mueller, Paul Cales, Vincenza Calvaruso, Adele Delamarre, Massimo Pinzani, Emmanuel A. Tsochatzis

MARC

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245 1 0 |a Agile scores in MASLD and ALD  |b External validation and their utility in clinical algorithms  |c Margarita Papatheodoridi, Victor De Ledinghen, Monica Lupsor-Platon, Fabrizio Bronte, Jerome Boursier, Omar Elshaarawy, Fabio Marra, Maja Thiele, Georgios Markakis, Audrey Payance, Edgar Brodkin, Laurent Castera, George Papatheodoridis, Aleksander Krag, Umberto Arena, Sebastian Mueller, Paul Cales, Vincenza Calvaruso, Adele Delamarre, Massimo Pinzani, Emmanuel A. Tsochatzis 
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520 |a Background & Aims - Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. - Methods - We included 4,243 patients (MASLD: 912, ALD: 386, CHB: 597, CHC: 2,348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. - Results - For F≥3, the diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs. 0.86, p = 0.831) and ALD (0.92 vs. 0.94, p = 0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs. 0.90, p = 0.412) and ALD (0.94 vs. 0.95, p = 0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% sensitivity/specificity, correct classification rates in MASLD were 66% vs. 61% using Agile 3+ vs. LS dual cut-offs and 71% vs. 67% in ALD, respectively. When using Agile 3+ or LSM as a second step after FIB-4 >1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs. 71%) and ALD (76% vs. 72%), with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. - Conclusion - Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis. - Impact and implications - As of today, it is accepted that there will be no single non-invasive test or an isolated cut-off for identifying patients with advanced chronic liver disease. Here, we confirmed that Agile 3+ and Agile 4 scores are useful alternatives to simple liver stiffness measurement in diagnosing advanced fibrosis/cirrhosis in steatotic liver disease, but they do not perform as well in chronic viral hepatitis. Agile scores can help optimize the diagnosis of advanced fibrosis/cirrhosis in a dual cut-off strategy by reducing the number of indeterminate results either alone or in a sequential strategy after FIB-4. The combination of Agile scores and liver stiffness measurement can further increase our confidence in a positive diagnosis of advanced fibrosis/cirrhosis. These novel combination strategies can be useful tools to predict the likelihood of advanced stages of liver disease with the highest possible accuracy in a secondary/tertiary healthcare setting. 
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