Introduction
Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (1). The most validated non-invasive method to assess liver steatosis and fibrosis is transient elastography (TE), whereas some new ultrasound-based technologies still lack substantial clinical evidence in this setting (2,3). In this line we aimed to evaluate performance of Shear Wave Measurement (SWM) and Attenuation (ATT) Measurement by Fujifilm to diagnose liver steatosis and fibrosis in the cohort of patients with T2DM, using TE as the reference.
Aims & Methods
Consecutive outpatients with T2D (N=147) were referred for controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) to assess the presence of liver steatosis and fibrosis by using TE. The presence of any grade of liver steatosis was considered in patients with CAP≥297 dB/m, and advanced fibrosis in those with LSM≥10 kPa by TE, which served as the reference method (4,5). All consented patients also underwent SWM and ATT (by Fujifilm Arietta 65), as the investigated methods, and their results were compared to LSM and CAP as measured by TE. All measurements were performed in fasting patients, whereas patients with conditions that might have influenced the results of LSM (ALT>5xULN, congestive liver disease, biliary obstruction, infiltrative liver neoplasms) were excluded.
Results
Of 147 included patients with T2D, 76 (51.7%) were females, average age 66, median Body Mass Index 30.5 kg/m2, 113 (76,9%) had arterial hypertension, 111 (75,5%) dyslipidemia, 27 (18.4%) were smokers, 26 (17.7%) reported risky alcohol consumption. As for TE, M probe was used in 104 (70.7%) patients, median LSM was 5.9 kPa, median CAP 290 dB/m. Any grade of steatosis (CAP≥297 dB/m) was detected in 62 (42,2%) patients, and advanced fibrosis (LSM≥10 kPa) in 17/145 (11.6%) patients by using TE. Median SWM was 5.5 kPa, and median ATT 0.62 dB/cm/MHz. We observed good correlation between LSM as measured by TE and SWM (Pearson's R=0.68, 95 CI: 0.58-0.76, p<0,001), whereas SWM produced lower (mean -0,7 unit, Bland-Altman) LSM values in comparison to TE. SWM had AUROC of 0.905 at the LSM cut-off ≥ 8.3 kPa (Youden) to diagnose advanced fibrosis (sen. 76.5%, specif. 93.8%). LSM by SWM optimized for ruling-in and ruling-out advanced fibrosis were respectively ≥10.1 kPa (specif. 97%) and <6.2 kPa (sens. 94.1%). Presence of advanced fibrosis would be missed in 23.5%, 41.2% and 5.8% patients by using reported LSM cut-offs (≥ 8.3, ≥10.1 and <6,2 kPa respectively). In multivariate analysis only platelet count (OR 0.979; CI 0.96-0.998, p=0.03) and LSM as measured by TE (OR 1.197; CI 1.031-1.391, p=0.02) were significantly associated with LSM measured by SWM. Correlation between ATT and CAP was poor (Pearson' R=0.31, 95 CI: 0.16-0.45, p<0.001), as was the overall diagnostic performance of ATT to diagnose any grade of liver steatosis (AUROC 0.673 at the cut-off ≥0.66 dB/cm/MHz (Youden); sens. 56.5%, specif. 75.3%). ATT cut-offs optimized for ruling-in and ruling-out any steatosis were ≥0.75 dB/cm/MHz (specif. 89.4%), and <0.50 dB/cm/MHz (sens. 88.7%) respectively. Presence of any steatosis would be missed in 43.5%, 62.9% and 11.2% by using reported ATT cut-offs (≥0.66, ≥0.75 and <0.50 dB/cm/MHz respectively).
Conclusion
SWM reliably recognizes presence of advanced liver fibrosis in patients with T2D. The diagnostic performance of ATT was suboptimal, and this should be further investigated by using more reliable reference methods, such as liver biopsy or magnetic resonance.
References
1. Leite NC, Villela-Nogueira CA, Pannain VLN et al. Histopathological stages of non-alcoholic fatty liver disease in type 2 diabetes: Prevalences and correlated factors. Liver Int. 2011 doi: 10.1111/j.1478-3231.2011.02482.x.
2. Tovo CV, Villela-Nogueira CA, Leite NC, Panke CL, Port GZ, Fernandes S, et al. Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Annals of Hepatology [Internet]. 2019 May [cited 2019 Dec 6];18(3):445–9.
3. Dietrich C, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, et al. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall in der Medizin - European Journal of Ultrasound. 2017 Apr 13;38(04):e16–47.
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