An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Clinical and Metabolic Evaluation
- Fatty liver index (FLI): (e0.953×loge (TG)+0.139×BMI+0.718×loge (GGT)+0.053×WC−15.745)/(1 + e0.953×loge (TG/0.0113)+0.139×BMI+0.718×loge (GGT)+0.053×WC−15.745) × 100 [14]
- Hepatic steatosis index (HSI):8 × ALT/AST ratio +BMI (+2, if DM; +2, if female) [15]
- Liver Fat Score (LFS): −2.89 + 1.18 × metabolic syndrome (yes = 1/no = 0) + 0.45 × Type 2 DM (yes = 2/no = 0) + 0.15 × FINS (mU/L) + 0.04 × AST(U/L) − 0.94 × AST/ALT [16]
- Visceral Adiposity Index (VAI) [17]Male: VAI = [WC/39.68 + (1.88 ×BMI)] × [TG/1.03] × (1.31/HDL)Female: VAI = [WC/36.58 + (1.89 × BMI)] × (TG/0.81) × (1.52/HDL)
- Triglycerides × Glucose index (TyG): ln [TG (mg/dL) × FBG (mg/dL)/2] [17]
2.3. Ultrasonography
2.4. Two-Dimensional Shear Wave Elastography (2D-SWE)
2.5. MRI-PDFF
2.6. Histological Assessment
2.7. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Clinical Characteristics of Subjects with Different Outcomes by Ultrasound
3.3. Factors Associated with Missed and Misdiagnosis with Ultrasound and Foundation of the Optimized Diagnostic Method
3.4. Validation of the New Strategy in the Liver Biopsy Cohort
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Non-MASLD by MRI-PDFF (n = 233) | MASLD by MRI-PDFF (n = 1256) | Non-MASLD by Biopsy (n = 226) | MASLD by Biopsy (n = 200) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Misdiagnosis (n = 145) | Non-Misdiagnosis (n = 88) | p | Missed Diagnosis (n = 77) | Non-Missed Diagnosis (n = 1179) | p | Misdiagnosis (n = 41) | Non-Misdiagnosis (n = 185) | p | Missed Diagnosis (n = 33) | Non-Missed Diagnosis (n = 167) | p | |
Age, years | 41 ± 12 | 43 ± 12 | 0.11 | 45 ± 14 | 41 ± 13 | 0.008 | 48 ± 15 | 52 ± 12 | 0.06 | 43 ± 12 | 42 ± 14 | 0.63 |
Male, n (%) | 70 (0.7) | 67 (0.8) | 0.12 | 56 (0.69) | 884 (0.72) | 0.53 | 25 (73.5) | 143 (77.3) | 0.63 | 28 (0.85) | 106 (0.61) | 0.008 |
Body mass index (BMI), kg/m2 | 23.8 ± 2.8 | 24.6 ± 3.5 | 0.12 | 26.4 ± 4.4 | 27.0 ± 4.0 | 0.23 | 27.9 ± 8.3 | 23.5 ± 2.8 | <0.001 | 25.6 ± 4.4 | 27.9 ± 5.9 | 0.05 |
BMI < 23 kg/m2, n (%) | 26 (0.26) | 18 (0.21) | 0.22 | 11 (0.14) | 143 (0.12) | 0.64 | 9 (26.5) | 76 (41.1) | 7 (0.21) | 25 (0.14) | ||
BMI 23–24.99 kg/m2, n (%) | 14 (0.14) | 20 (0.23) | 15 (0.18) | 188 (0.15) | 7 (20.6) | 69 (37.3) | <0.001 | 8 (0.24) | 40 (0.23) | 0.65 | ||
BMI ≥ 25 kg/m2, n (%) | 60 (0.60) | 46 (0.55) | 55 (0.68) | 893 (0.73) | 18 (52.9) | 40 (21.6) | 18 (0.55) | 109 (0.63) | ||||
Diabetes mellitus (%) | 4 (0.04) | 5 (0.06) | 0.53 | 4 (0.05) | 97 (0.08) | 0.33 | 2 (5.9) | 16 (8.6) | 0.65 | 5 (15.2) | 24 (13.8) | 0.83 |
Abdominal circumference, cm | 86.7 ± 8.2 | 88.2 ± 10.2 | 0.32 | 92.6 ± 10.4 | 94.0 ± 9.6 | 0.22 | 97.8 ± 20.7 | 84.8 ± 9.0 | <0.001 | 91.6 ± 10.0 | 98.8 ± 16.6 | 0.02 |
Hypertension (%) | 69 (0.69) | 59 (0.70) | 0.93 | 54 (0.67) | 856 (0.70) | 0.52 | 15 (44.1) | 94 (50.8) | 0.55 | |||
Systolic pressure, mmHg | 125 ± 15 | 130 ± 16 | 0.02 | 129 ± 13 | 131 ± 16 | 0.24 | 127 ± 10 | 130 ± 13 | 0.08 | 131 ± 13 | 130 ± 16 | 0.65 |
Diastolic pressure, mmHg | 82 ± 11 | 85 ± 11 | 0.52 | 85 ± 10 | 86 ± 12 | 0.46 | 78 ± 9 | 84 ± 10 | 0.001 | 87 ± 12 | 83 ± 11 | 0.04 |
Metabolic syndrome (%) | 31 (0.31) | 20 (0.24) | 0.43 | 23 (0.28) | 596 (0.49) | <0.001 | 13 (38.2) | 22 (11.9) | 0.001 | 22 (66.7) | 91 (52.3) | 0.13 |
Alanine aminotransferase, U/L | 35.1 ± 32.0 | 32.9 ± 23.3 | 0.62 | 43.3 ± 36.4 | 58.1 ± 49.4 | 0.008 | 59.2 ± 46.5 | 58.1 ± 71 | 0.95 | 74.5 ± 41.6 | 83.4 ± 56.1 | 0.56 |
Aspartate aminotransferase, U/L | 30.0 ± 21.5 | 30.9 ± 18.4 | 0.72 | 34.4 ± 34.0 | 40.1 ± 34.4 | 0.15 | 45.4 ± 29.1 | 64.2 ± 73.9 | 0.14 | 44.8 ± 16.3 | 52.3 ± 41.3 | 0.37 |
Alkaline phosphatase, U/L | 75.8 ± 20.0 | 79.8 ± 24.7 | 0.23 | 80.7 ± 25.1 | 81.2 ± 31.2 | 0.93 | 104.0 ± 62.6 | 99.1 ± 45.6 | 0.63 | 86.0 ± 15.9 | 93.1 ± 46.9 | 0.47 |
Glutamate transpeptidase, U/L | 47.9 ± 61.5 | 52.2 ± 60.7 | 0.63 | 55.5 ± 69.3 | 64.6 ± 77.4 | 0.35 | 84.6 ± 78.2 | 83.6 ± 78.6 | 0.93 | 105.0 ± 59.0 | 89.2 ± 93.1 | 0.37 |
Uric acid, μmol/L | 381 ± 89 | 346 ± 76 | 0.002 | 398 ± 96 | 425 ± 104 | 0.02 | 378 ± 118 | 334 ± 82 | 0.005 | 413 ± 61 | 417 ± 132 | 0.84 |
Cholesterol, mmol/L | 4.9 ± 1.0 | 5.1 ± 1.1 | 0.12 | 5.1 ± 1.0 | 5.2 ± 1.1 | 0.23 | 4.8 ± 1.0 | 4.7 ± 1.1 | 0.63 | 5.3 ± 0.9 | 5.1 ± 1.0 | 0.26 |
Triglyceride, mmol/L | 1.3 ± 0.7 | 1.4 ± 0.7 | 0.11 | 1.6 ± 1.0 | 2.0 ± 1.3 | 0.02 | 1.3 ± 0.5 | 1.1 ± 0.4 | 0.002 | 2.5 ± 2.8 | 2.1 ± 1.5 | 0.23 |
High-density lipoprotein, mmol/L | 1.2 ± 0.3 | 1.3 ± 0.3 | 0.24 | 1.3 ± 0.4 | 1.2 ± 0.4 | 0.14 | 1.4 ± 0.7 | 1.7 ± 1.8 | 0.34 | 1.1 ± 0.2 | 1.1 ± 0.5 | 0.54 |
Low-density lipoprotein, mmol/L | 3.1 ± 0.8 | 3.2 ± 0.8 | 0.44 | 3.2 ± 0.7 | 3.2 ± 0.8 | 0.26 | 2.8 ± 0.8 | 2.7 ± 0.9 | 0.66 | 3.4 ± 0.8 | 3.2 ± 0.7 | 0.15 |
Fasting blood glucose, mmol/L | 4.8 ± 0.6 | 5.2 ± 1.9 | 0.04 | 4.9 ± 0.8 | 5.2 ± 1.1 | 0.02 | 5.4 ± 1.0 | 5.5 ± 1.4 | 0.75 | 5.8 ± 1.0 | 5.5 ± 1.8 | 0.46 |
Fasting insulin, μU/ml | 8.9 ± 5.0 | 8.5 ± 4.2 | 0.55 | 10.5 ± 6.0 | 12.1 ± 7.1 | 0.06 | 14.4 ± 9.0 | 10.5 ± 8.4 | 0.01 | 15.3 ± 5.8 | 16.7 ± 10.9 | 0.55 |
HOMA–insulin resistance | 1.9 ± 1.1 | 2.0 ± 1.4 | 0.72 | 2.3 ± 1.5 | 2.8 ± 2.0 | 0.03 | 3.6 ± 2.7 | 2.6 ± 2.4 | 0.02 | 4.1 ± 1.9 | 4.2 ± 3.1 | 0.86 |
Liver fat content of MRI-PDFF Mild steatosis (%) | 6.3 ± 4.9 - | 3.9 ± 1.1 - | <0.05 - | 8.9 ± 4.7 73 (0.90) | 15.1 ± 8.1 737 (0.60) | <0.001 | - | - | - | - | - | - |
Moderate steatosis, n (%) | - | - | - | 3 (0.04) | 190 (0.16) | <0.001 | ||||||
Severe steatosis, n (%) | - | - | - | 5 (0.06) | 297 (0.24) | |||||||
Thickness of subcutaneous fat, cm | 22.0 ± 7.0 | 23.5 ± 7.6 | 0.43 | 24.6 ± 8.6 | 23.9 ± 8.3 | 0.56 | ||||||
Liver stiffness with SWE, kpa, | 6.0 ± 3.1 | 6.4 ± 2.6 | 0.42 | 6.5 ± 2.5 | 6.5 ± 2.9 | 0.94 | 13.6 ± 11.1 | 16.2 ± 8.2 | 0.24 | 6.9 ± 2.5 | 7.0 ± 3.6 | 0.93 |
Controlled attenuation parameter | 260 ± 44 | 258 ± 43 | 0.82 | 262 ± 40 | 290 ± 49 | 0.002 | - | - | - | - | - | - |
Liver stiffness measurement | 5.8 ± 2.6 | 6.8 ± 4.1 | 0.24 | 6.6 ± 2.7 | 8.0 ± 13.8 | 0.64 | - | - | - | - | - | - |
Fatty liver index | 31.2 ± 21.4 | 38.6 ± 24.0 | 0.25 | 47.2 ± 26.2 | 56.5 ± 23.7 | 0.001 | 56.2 ± 32.0 | 35.2 ± 22.2 | <0.001 | 65.1 ± 22.8 | 68.0 ± 24.1 | 0.54 |
Hepatic steatosis index | 34.4 ± 5.0 | 34.4 ± 5.0 | 0.92 | 37.6 ± 6.3 | 38.9 ± 6.7 | 0.15 | 40.1 ± 12.3 | 32.4 ± 4.7 | <0.001 | 39.3 ± 7.0 | 42.7 ± 10.1 | 0.07 |
Liver fat score | −1.1 ± 1.5 | −1.1 ± 1.4 | 0.94 | −0.44 ± 1.8 | 0.38 ± 2.1 | 0.001 | 0.6 ± 2.3 | 0.2 ± 3.3 | 0.54 | 1.4 ± 1.8 | 1.7 ± 2.5 | 0.67 |
Visceral adiposity index | 1.6 ± 1.2 | 1.8 ± 1.6 | 0.46 | 1.9 ± 1.3 | 2.6 ± 2.4 | 0.01 | 1.7 ± 1.0 | 1.2 ± 0.9 | 0.002 | 3.8 ± 6.3 | 3.2 ± 2.6 | 0.37 |
Triglycerides × glucose index | 8.4 ± 0.5 | 8.6 ± 0.5 | 0.03 | 8.5 ± 0.5 | 8.8 ± 0.6 | <0.001 | 8.5 ± 0.4 | 8.4 ± 0.4 | 0.01 | 9.2 ± 0.6 | 8.9 ± 0.6 | 0.05 |
Variables | Study Cohort | Validation Cohort | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Univariate | Multivariate | Univariate | Multivariate | ||||||||
OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | ||||
Body mass index (BMI) | <0.001 | <0.001 | |||||||||
BMI < 23 kg/m2 | reference | reference | |||||||||
BMI 23–24.99 kg/m2 | 1.67 (0.96–2.92) | 0.07 | 1.67 (0.96–2.92) | 0.07 | |||||||
BMI ≥ 25 kg/m2 | 6.64 (3.94–11.2) | <0.001 | 6.64 (3.94–11.2) | <0.001 | |||||||
Abdominal obesity | 5.10 (3.37–7.72) | <0.001 | 5.10 (3.37–7.72) | <0.001 | |||||||
Hypertension | 3.61 (2.60–5.03) | <0.001 | 13.34 (7.92–22.50) | <0.001 | |||||||
Triglyceride > 1.7 mmol/L | 2.41 (1.72–3.35) | <0.001 | 3.94 (2.57–6.05) | <0.001 | |||||||
Low–High-density lipoprotein | 2.16 (1.62–2.87) | <0.001 | 1.42 (0.97–2.09) | 0.07 | |||||||
Impaired glucose metabolism | 2.41 (1.55–3.75) | <0.001 | 0.98 (0.66–1.45) | 0.92 | |||||||
Number of Mets components | 2.52 (2.16–2.93) | <0.001 | 2.32 (1.96–2.76) | <0.001 | 2.75 (2.22–3.41) | <0.001 | 2.43 (1.87–3.16) | <0.001 | |||
Metabolic syndrome | 4.28 (2.96–6.18) | <0.001 | 7.54 (4.77–11.90) | 0.002 | |||||||
Alanine aminotransferase > 1 × ULN | 3.66 (2.74–4.88) | <0.001 | 2.20 (1.58–3.08) | <0.001 | 2.54 (1.49–4.30) | 0.001 | 2.25 (1.00–5.05) | <0.001 | |||
Uric acid > 1 × ULN | 3.47 (2.53–4.77) | <0.001 | 1.87 (1.31–2.69) | <0.001 | 5.40 (3.52–8.30) | <0.001 | 2.68 (1.49–4.83) | 0.001 | |||
Cholesterol > 5.7 mmol/L | 1.43 (1.02–1.99) | 0.04 | 1.84 (1.11–3.07) | 0.02 | |||||||
HOMA–insulin resistance > 3.0 | 3.15 (2.07–4.79) | <0.001 | 3.59 (2.40–5.35) | <0.001 |
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Feng, X.; Ye, J.; Deng, H.; Li, X.; Xu, L.; Feng, S.; Dong, Z.; Liao, B.; Dong, Z.; Zhong, B. An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease. Diagnostics 2023, 13, 3503. https://doi.org/10.3390/diagnostics13233503
Feng X, Ye J, Deng H, Li X, Xu L, Feng S, Dong Z, Liao B, Dong Z, Zhong B. An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease. Diagnostics. 2023; 13(23):3503. https://doi.org/10.3390/diagnostics13233503
Chicago/Turabian StyleFeng, **ongcai, Junzhao Ye, Hong Deng, **n Li, Lishu Xu, Shiting Feng, Zhi Dong, Bing Liao, Zhiyong Dong, and Bihui Zhong. 2023. "An Optimized Strategy Based on Conventional Ultrasound for Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease" Diagnostics 13, no. 23: 3503. https://doi.org/10.3390/diagnostics13233503