Controlled attenuation parameter factors and steatosis grading in metabolic dysfunction-associated steatotic liver disease

Abstract

Aim: To identify factors influencing liver-controlled attenuation parameter (CAP, dB/m) and establish its optimal diagnostic thresholds for hepatic steatosis grading in metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: A total of 758 prospectively enrolled MASLD patients at Zhongshan Hospital, Shanghai, China (September 2022-June 2023) were randomized into a training cohort (n = 619) and a validation cohort (n = 139), stratified by body mass index (BMI: normal-weight < 25 kg/m²; overweight ≥ 25 kg/m²). Demographics, laboratory parameters, CAP, and magnetic resonance imaging (MRI) proton density fat fraction (PDFF) were recorded. Using MRI-derived PDFF (MRI-PDFF) as the reference, receiver operating characteristic (ROC) analysis was performed to establish CAP thresholds for steatosis grades.

Results: In the training cohort, multivariate analysis showed that CAP was correlated with uric acid, glucose, and high-density lipoprotein (HDL) in normal-weight patients, and with alanine aminotransferase (ALT), total cholesterol (TC), and BMI in overweight patients. Overall cohort CAP thresholds were: S1, 283.5 dB/m [area under the curve (AUC) = 0.880]; S2, 311.5 dB/m (AUC = 0.712); S3, 328.5 dB/m (AUC = 0.799). Normal-weight thresholds: S1, 259.5 dB/m (AUC = 0.922); S2-3, 323.5 dB/m (AUC = 0.779). Overweight thresholds: S1, 304.0 dB/m (AUC = 0.829); S2, 311.5 dB/m (AUC = 0.677); S3, 328.5 dB/m (AUC = 0.767). Validation confirmed robust diagnostic performance.

Conclusion: CAP correlates significantly with metabolic factors (glucose, HDL) and shows a trend toward association with uric acid (P = 0.073) in normal-weight MASLD patients, and with liver markers/metabolic factors (BMI, ALT, TC) in overweight patients. CAP demonstrates good diagnostic accuracy for grading the severity of hepatic steatosis in MASLD, particularly for mild to moderate steatosis.

Highlights

1. Study of 758 MASLD patients stratified by BMI to identify factors influencing CAP and its diagnostic value for hepatic steatosis, using MRI-derived PDFF as reference.
2. CAP correlates with glucose, HDL, and uric acid in normal-weight patients, and with ALT, total cholesterol (TC), and BMI in overweight patients.
3. BMI-specific CAP thresholds were established, with the highest diagnostic performance in normal-weight individuals (AUC = 0.922 for S1).
4. Validation confirmed robust diagnostic accuracy (Youden index 0.81-0.83), supporting CAP as a practical non-invasive tool for grading mild-to-moderate steatosis.

Keywords

Controlled attenuation parameter / metabolic dysfunction-associated steatotic liver disease / normal weight / overweight / correlation analysis

References

[1] Friedman SL,Rinella M.Mechanisms of NAFLD development and therapeutic strategies.Nat Med2018;24:908-22 PMCID:PMC6553468

[2] Younossi ZM,Paik JM,Van Dongen C.The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review.Hepatology2023;77:1335-47 PMCID:PMC10026948

[3] Rinella ME.Nonalcoholic fatty liver disease: a systematic review.JAMA2015;313:2263-73

[4] Targher G,Byrne CD.Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach.Lancet Gastroenterol Hepatol2021;6:578-88

[5] Masoodi M,Hyötyläinen T.Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests.Nat Rev Gastroenterol Hepatol2021;18:835-56

[6] Tincopa MA.Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.Lancet Gastroenterol Hepatol2023;8:660-70

[7] Saadeh S,Remer EM.The utility of radiological imaging in nonalcoholic fatty liver disease.Gastroenterology2002;123:745-50

[8] Ratziu V, Charlotte F, Heurtier A, et al; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898-906.

[9] Reeder SB,Hamilton G.Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy.J Magn Reson Imaging2011;34:729-49 PMCID:PMC3177109

[10] Sirli R.Controlled attenuation parameter for quantification of steatosis: which cut-offs to use?.Can J Gastroenterol Hepatol2021;2021:6662760 PMCID:PMC8018863

[11] Karlas T,Sasso M.Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol2017;66:1022-30

[12] Jan A. BMI classification percentile and cut off points. Available from: https://www.researchgate.net/publication/337153906_BMI_Classification_Percentile_And_Cut_Off_Points. [Last accessed on 6 Jan 2026].

[13] Li Y,Xie T.The correlation of body mass index (BMI) and transient elastography parameters.Journal of Rare Diseases2022;29:101-3. (in Chinese)

[14] Society of Hepatology, Chinese Medical Association. [Guidelines for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (Version 2024)].Zhonghua Gan Zang Bing Za Zhi2024;32:418-34. (in Chinese)

[15] Duan Y,Luo J.Association of inflammatory cytokines with non-alcoholic fatty liver disease.Front Immunol2022;13:880298 PMCID:PMC9122097

[16] Estes C,Arias-Loste MT.Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.J Hepatol2018;69:896-904

[17] Rinella ME,Siddiqui MS.AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.Hepatology2023;77:1797-835 PMCID:PMC10735173

[18] Eslam M,Wong VW.The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.Hepatol Int2020;14:889-919

[19] Beyer C,Andersson A.Comparison between magnetic resonance and ultrasound-derived indicators of hepatic steatosis in a pooled NAFLD cohort.PLoS One2021;16:e0249491 PMCID:PMC8016312

[20] Ferraioli G,Savietto G.Performance of the attenuation imaging technology in the detection of liver steatosis.J Ultrasound Med2021;40:1325-32 PMCID:PMC8246860

[21] Petroff D,Newsome PN.Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.Lancet Gastroenterol Hepatol2021;6:185-98

[22] Myers RP,Kirsch R.Controlled attenuation parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography.Liver Int2012;32:902-10

[23] Kumar M,Singh T.Controlled attenuation parameter for non-invasive assessment of hepatic steatosis: does etiology affect performance?.J Gastroenterol Hepatol2013;28:1194-201

[24] Chon YE,Kim SU.Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population.Liver Int2014;34:102-9

[25] Masaki K,Hyogo H.Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases.Hepatol Res2013;43:1182-9

[26] Chan WK,Mahadeva S.Controlled attenuation parameter for the detection and quantification of hepatic steatosis in nonalcoholic fatty liver disease.J Gastroenterol Hepatol2014;29:1470-6

[27] Zhou Y,Qiao Q.Correlation between body fat distribution measured by quantitative CT and body mass index in adults receiving physical examination.Chin J Health Manag2024;18:354-60. (in Chinese)

[28] Sporea I,Mare R,Ivașcu SC.Feasibility of Transient Elastography with M and XL probes in real life.Med Ultrason2016;18:7-10

[29] Recio E,Macías J.Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.Eur J Gastroenterol Hepatol2013;25:905-11