Calculator for screening of advanced fibrosis in MASLD version 1.05                      gilles.hunault "at" univ-angers.fr This file provides a calculator to stage liver fibrosis according to Kleiner system (1), especially to screen advanced liver fibrosis (F3 or F4 Kleiner) (1) in patients at risk of MASLD (i.e. having at least one metabolic risk factor like obesity or diabetes (T2DM)). It can be used for a single patient or a data base. The first line test for screening is FIB-9 including 9 usual blood markers from the routine liver function test: AST, ALT, GGT, alkaline phosphatases (ALP), bilirubin, albumin, platelets, prothrombin index (%) (or INR) and urea (this variable can be omitted). They are adjusted on age, weight, height and diabetes. This FIB-9 calculator provides some clinical comments along with the fibrosis score reflecting the Kleiner fibrosis stage (1) and accuracy estimation. It can replace or complete FIB-4 (2, 3) since its diagnostic indices were better, e.g. AUROC for advanced fibrosis was 0.863 vs 0.757 (p<0.001) in an internal validation population of 414 patients with MASLD (4). Indications:  patients with at least one metabolic factor (obesity, diabetes...) whatever the blood level of liver enzymes. Reassess advanced fibrosis estimation periodically in patients without advanced fibrosis on previous estimation:  every 1 to 2 years if T2DM / pre T2DM or ≥ 2 metabolic risk factors every 2 to 3 years otherwise Relative contra-indications:  the following variables were responsible for a significant decrease in FIB-9 accuracy (accuracy ≤ 57%) at their extreme values: age ≥ 80 yr, AST ≥ 300 IU/l (or ALT ≥ 400 IU/l), alkaline phosphatases ≤ 35 IU/l (4). Therefore, results should cautiously be interpreted for those values. Nevertheless, a reliability analysis is included for all cases. Missing value: as urea is usually not included in liver function tests, it is possible to calculate FIB-9 without urea. Indeed, the corresponding FIB-8 had a non-significant decrease in AUROC for advanced fibrosis in the validation set (-0.5%, p=0.619) (4). It that case, sex value is necessary. Interpretation: The FIB-9 score was derived by AI in a population of 637 patients with MASLD and validated in a different internal population of 414 patients (4). Pending appropriate external validation, FIB-9 results should be interpreted with caution based on clinical and local epidemiological data. Example of clinical interpretation of FIB-9 score: a score between >1.5 and <2.5 indicates a Kleiner F2 stage; a score at around 2.5 indicates a transition from Kleiner F2 to F3 stages. Calculator created by Gilles Hunault. Author responsible for this content: Pr. Paul CALÈS, Angers University (France). ORCID: https://orcid.org/0000-0003-4866-5274 Version date: January 2025. References: 1. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-1321. 2. European Association for the Study of the Liver, Berzigotti A, Boursier J, Castera L, Cazzagon N, et al. EASL Clinical Practice Guidelines On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2021 Update. J Hepatol 2021;75:659-689. 3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 2023;77:1797-1835. 4. Calès P, Canivet CM, Costentin C, Lannes A, Oberti F, Fouchard I, Hunault G, de Lédinghen V, Boursier J. A new generation of non-invasive tests of liver fibrosis with improved accuracy in MASLD. J Hepatol 2025. https://doi.org/10.1016/j.jhep.2024.11.049. 5. Cales P, Tuffigo M, Oberti F, Planche V, Boursier J, Fouchard Hubert I, et al. Clinical comparison and conversion of international normalized ratio and prothrombin index. J Hepatol 2019; 70: e814-e815.

 

 

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