Article, 2024
AGILE SCORES IN MASLD AND ALD: EXTERNAL VALIDATION AND THEIR UTILITY IN CLINICAL ALGORITHMS
Journal of Hepatology,
ISSN
1600-0641,
0168-8278,
10.1016/j.jhep.2024.05.021
Contributors
Papatheodoridi, Margarita
[1]
[2]
De Ledinghen, Victor
[3]
Lupsor-Platon, Monica
0000-0001-7918-1956
[4]
Bronte, Fabrizio
0000-0003-0896-830X
[5]
Boursier, Jérôme
0000-0002-7282-1436
[6]
Elshaarawy, Omar
0000-0002-6945-6204
[7]
[8]
[9]
Marra, Fabio
0000-0001-8629-0878
[10]
Thiele, Maja Sofie
0000-0003-1854-1924
[11]
Markakis, Georgios
0000-0001-6336-6155
[2]
Payancé, Audrey
[12]
Brodkin, Edgar
[1]
Castera, Laurent
0000-0002-6715-8588
[12]
[13]
Papatheodoridis, George Vasileios
0000-0002-3518-4060
[2]
Krag, Aleksander Ahm
0000-0002-9598-4932
[11]
Arena, Umberto
0000-0001-6635-2568
[10]
Mueller, Sebastian
0000-0001-5790-0841
[9]
Calès, Paul
0000-0003-4866-5274
[6]
Calvaruso, Vincenza
0000-0002-0287-1059
[5]
Delamarre, Adèle
0000-0002-6761-2656
[3]
Pinzani, Massimo
0000-0003-1398-1541
[1]
Tsochatzis, Emmanuel A
0000-0001-5069-2461
(Corresponding author)
[1]
Affiliations
- [1]
University College London
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [2]
Laiko General Hospital of Athens
[NORA names:
Greece; Europe, EU; OECD];
- [3]
University of Bordeaux
[NORA names:
France; Europe, EU; OECD];
- [4]
Iuliu Hațieganu University of Medicine and Pharmacy
[NORA names:
Romania; Europe, EU];
- [5]
University of Palermo
[NORA names:
Italy; Europe, EU; OECD];
(... more)
- [6]
Centre Hospitalier Universitaire d'Angers
[NORA names:
France; Europe, EU; OECD];
- [7]
Menoufia University
[NORA names:
Egypt; Africa];
- [8]
University of Liverpool
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [9]
Heidelberg University
[NORA names:
Germany; Europe, EU; OECD];
- [10]
University of Florence
[NORA names:
Italy; Europe, EU; OECD];
- [11]
Odense University Hospital
[NORA names:
Region of Southern Denmark;
Hospital; Denmark; Europe, EU; Nordic; OECD];
- [12]
Beaujon Hospital
[NORA names:
France; Europe, EU; OECD];
- [13]
Center for Research on Inflammation
[NORA names:
France; Europe, EU; OECD]
(less)
Abstract
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.
Keywords
Agile 3,
Agile 4,
F4,
FIB-4,
accuracy,
advanced chronic liver disease,
advanced fibrosis,
advanced fibrosis/cirrhosis,
advanced stages of liver disease,
agility,
agility score,
agreement,
aim,
alcohol-related liver disease,
algorithm,
biomarkers,
biopsy,
chronic hepatitis B or C,
chronic liver disease,
chronic viral hepatitis,
cirrhosis,
classification,
classification rate,
clinical algorithm,
combination,
combination strategies,
confidence,
cut-off,
diagnosis,
diagnostic accuracy,
disease,
fibrosis,
fibrosis/cirrhosis,
gt;1.3,
healthcare settings,
hepatitis,
hepatitis B or C,
implications,
indeterminate results,
laboratory,
laboratory tests,
likelihood,
liver,
liver biopsy,
liver disease,
liver stiffness measurement,
measurements,
months,
non-invasive tests,
patients,
positive agreement,
positive diagnosis,
rate,
results,
scores,
sensitivity/specificity,
sequential strategy,
sequential use,
sets,
specificity,
stage of liver disease,
steatotic liver disease,
stiffness measurement,
strategies,
test,
threshold,
use,
viral hepatitis
Data Provider: Digital Science