Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Design and Setting
4.2. Population Study
4.3. Anthropometric Measurements and Blood Pressure
4.4. Assay Methods: Hormonal and Metabolic Profile
4.5. Cardio-Metabolic and Liver Indices
4.6. Diagnosis of Liver Steatosis
4.7. Fibroscan and Controlled Attenuation Parameter Evaluation
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Patients (N. 48) | |
---|---|---|
Age | 43.1 ± 14.2 | |
Sex | Males (%) | 6 (12.5%) |
Females (%) | 42 (87.5%) | |
Height (m) | 1.61 [1.57; 1.68] | |
Weight (kg) | 103.5 [91.7; 116.3] | |
BMI (kg/m2) | 40.21 [34; 43.1] | |
BMI classes | Overweight (%) | 5 (10.4%) |
Class I Obesity (%) | 9 (18.7%) | |
Class II Obesity (%) | 8 (16.7%) | |
Class III Obesity (%) | 26 (54.2%) | |
WC Males (<102 cm) WC Females (<88 cm) | 121 ± 15.9 107.7 ± 14.3 | |
Blood Pressure | ||
SBP (≤130 mmHg) | 127.5 [120; 140] | |
DPB (≤85 mmHg) | 80 [75; 85] | |
Fasting Glucose (n.v. ≤ 110 mg/dL) | 88 [80; 97] | |
Fasting Insulin (n.v. 3–25 μU/mL) | 20.3 [11.2; 25.9] | |
HbA1c(n.v. < 6.5%) | 5.6 [5.3; 5.8] | |
HoMA-IR (n.v. < 2.5) | 4.34 [2.36; 5.8] | |
Total Cholesterol (n.v. < 190 mg/dL) | 179 [156; 197] | |
HDL-Cholesterol (males > 40 mg/dL; females >50 mg/dL) | 47 [40; 56] | |
LDL-Cholesterol (≤130 mg/dL) | 108.3 [93.25; 125.65] | |
Triglycerides (n.v. ≤ 150 mg/dL) | 112 [86; 166] | |
AST (n.v. 0–34 U/L) | 19 [15; 25] | |
ALT n.v. 0–55 U/L) | 21 [16; 32] | |
γGT (n.v. 9–36 U/L) | 22 [13; 33] | |
hsCRP (0.57–2.59 mg/L) | 0.57 [0.33; 0.91] | |
Transient Elastography Parameters | ||
Liver Steatosis | Absent (%) | 3 (6.3%) |
Mild (%) | 8 (16.7%) | |
Moderate (%) | 9 (18.7%) | |
Severe (%) | 28 (58.3%) | |
Stiffness (n.v. 2–4 kPa) | 5.6 [4.35; 7.73] | |
% patients ≥ 4 kPa | 60.4% | |
% patients in different Stiffness categories | F1 ≤ 7.5 | 38 (79.2%) |
7.5 < F2 ≤ 10 | 2 (4.2%) | |
10 < F3 ≤ 14 | 4 (8.3%) | |
F4 ≥ 14 | 4 (8.3%) | |
CAP (n.v. < 237 dB/m) | 316 [273.25; 367] | |
Steatosis and Fibrosis LiverIndices | ||
FLI (n.v. < 60) | 93.6 [55.2; 99.04] | |
n. patients > 60 | 47 | |
FIB-4 (n.v. < 3.25) | 0.64 [0.17; 1.89] | |
APRI (n.v. < 1) | 0.21 [0.16; 0.25] | |
Cytokeratin-18 | ||
CK18M30 (n.v. < 251 U/L) | 56.4 [31.5; 75.4] | |
CK18M65 (n.v. < 413 U/L) | 188.5 [137.3; 230.3] |
Parameters | CK18M30 | CK18M65 | ||
---|---|---|---|---|
R | p values | r | p values | |
BMI | r = 0.66 | p < 0.001 | r = 0.65 | p < 0.001 |
WC | r = 0.77 | p < 0.001 | r = 0.76 | p < 0.001 |
AST | r = 0.95 | p < 0.001 | r = 0.95 | p < 0.001 |
ALT | r = 0.98 | p < 0.001 | r = 0.97 | p < 0.001 |
Stiffness | r = 0.67 | p < 0.001 | r = 0.71 | p < 0.001 |
HOMA-IR | r = 0.92 | p < 0.001 | r = 0.91 | p < 0.001 |
APRI | r = 0.69 | p < 0.001 | r = 0.72 | p < 0.001 |
a | |||||||
CK18M30 ≤ µe (n = 25) | CK18M30 > µe (n = 23) | p-Values | CK18M65 ≤ µe (n = 24) | CK18M65 > µe (n = 24) | p-Values | ||
Age | 41 ± 13.4 | 45.7 ± 14.6 | 0.252 a | 42.5 ± 13.7 | 44 ± 14.6 | 0.730 a | |
Sex | M (%) F (%) | 1 (2.08%) 24 (50%) | 5 (10.42%) 18 (37.5%) | 0.063 χ2 | 2 (4.2%) 22 (45.8%) | 4 (8.3%) 20 (41.7%) | 0.383 χ2 |
Prediabetes | No (%) Yes (%) | 16 (33.3%) 9 (18.8%) | 13 (27.1%) 10 (8.3%) | 0.769 χ2 | 17 (35.4%) 7 (14.6%) | 13 (27.1%) 11 (22.9%) | 0.238 χ2 |
Hypertension | No (%) Yes (%) | 17 (35.4%) 8 (16.7%) | 9 (18.7%) 14 (29.2%) | 0.045 χ2 | 13 (27.1%) 11 (22.9%) | 13 (27.1%) 11 (22.9%) | 0.999 χ2 |
Dyslipidemia | No (%) Yes (%) | 10 (32.3%) 8 (25.8%) | 7 (22.6%) 6 (19.3%) | 0.925 χ2 | 10 (32.2%) 7 (22.6%) | 7 (22.6%) 7 (22.6%) | 0.725 χ2 |
Metabolic Syndrome | No (%) Yes (%) | 13 (27%) 12 (25%) | 11 (23%) 12 (25%) | 0.773 χ2 | 14 (29%) 10 (21%) | 10 (21%) 14 (29%) | 0.248 χ2 |
BMI (kg/m2) | 39 [31.6; 42.5] | 41 [34.7; 45] | 0.297 a | 38.5 [31.6; 42.1] | 41.1 [36.3; 46] | 0.103 a | |
Overweight (%) Class I (%) Class II (%) Class III (%) | 2 (4.2%) 6 (12.5%) 6 (12.5%) 11 (22.9%) | 3 (6.2%) 3 (6.2%) 2 (4.2%) 15 (31.3%) | 0.471 χ2 | 2 (4.2%) 7 (14.6%) 4 (8.3%) 11 (22.9%) | 3 (6.3%) 2 (4.2%) 4 (8.3%) 15 (31.2%) | 0.341 | |
WC (cm) | 109 [99; 120] | 120 [109; 136] | 0.042 b | 111 [98.5; 120] | 118 [106; 136] | 0.054 a | |
SBP (mmHg) | 130 [120; 138] | 125 [120; 140] | 0.998 a | 125 [120; 130] | 130 [120; 140] | 0.656 a | |
DBP (mmHg) | 80 [75; 85] | 80 [80; 90] | 0.223 a | 80 [75; 85] | 80 [80; 90] | 0.406 a | |
Fasting Glucose (mg/dL) | 85 [76; 94.5] | 91 [81; 100] | 0.224 a | 84 [76; 96] | 91.5 [83.5; 97.8] | 0.227 a | |
Fasting Insulin (mg/dL) | 17.7 [10.2; 24.7] | 22.5 [18.5; 27.9] | 0.098 b | 17.4 [10.4; 22.4] | 23 [17.3; 29.7] | 0.055 b | |
HbA1c (%) | 5.35 [5.2; 5.7] | 5.6 [5.48; 5.83] | 0.039 b | 5.3 [5.2; 5.7] | 5.7 [5.6; 5.85] | 0.01 b | |
HoMA-IR (n.v. < 2.5) | 3.36 [1.97; 5.47] | 5.31 [3.79; 6.04] | 0.059 b | 3.27 [2.12; 4.46] | 5.32 [4.01; 6.92] | 0.03 b | |
Total Cholesterol (mg/dL) | 179 [157; 196] | 182 [156; 206] | 0.847 a | 183 [160; 197] | 176 [155; 198] | 0.861 a | |
HDL-Cholesterol (mg/dL) | 48 [40.5; 58] | 44 [39; 53] | 0.507 a | 47.5 [41.3; 58.8] | 43.5 [38.3; 50.8] | 0.18 a | |
LDL-Cholesterol (mg/dL) | 107 [96.1; 126] | 110 [84.6; 126] | 0.95 a | 110 [99.4; 127] | 108 [84.7; 124] | 0.672 a | |
Triglycerides (mg/dL) | 103 [79; 166] | 124 [95; 180] | 0.154 b | 103 [78.5; 161] | 124 [92; 172] | 0.236 b | |
AST (U/L) | 17 [14.5; 22] | 20 [16; 28] | 0.059 b | 18.5 [12.5; 23.8] | 25 [16.5; 48.8] | 0.018 b | |
ALT (U/L) | 19 [13; 24] | 26 [18; 36] | 0.032 b | 19 [14; 27.8] | 26 [13.8; 42.3] | 0.16 b | |
γGT (U/L) | 19 [13; 30] | 25 [14; 34] | 0.288 b | 1.6 [1.05; 2.4] | 2.8 [2.08; 3.23] | 0.005 b | |
hsCRP (mg/l) | 0.58 [0.33; 1.4] | 0.65 [0.33; 1.3] | 0.999 b | 0.59 [0.33; 0.9] | 0.61 [0.35; 1.38] | 0.772 b | |
b | |||||||
CK18M30 ≤ µe (n = 25) | CK18M30 > µe (n = 23) | p-Values | CK18M65 ≤ µe (n = 24) | CK18M65 > µe (n = 24) | p-Values | ||
Transient Elastography Parameters | |||||||
Liver Steatosis | Absent (%) Mild (%) Moderate(%) Severe (%) | 0 (0%) 2 (5.6%) 4 (11.1%) 11(30.6%) | 1 (2.8%) 3 (8.3%) 2 (5.6%) 13 (36%) | 0.587 χ2 | 0 (0%) 2 (5.4%) 4 (10.8%) 11 (29.7%) | 1 (2.7%) 3 (8.1%) 2 (5.4%) 14(37.9%) | 0.573 χ2 |
Stiffness (v.n. < 4 kPa) | 5.5 [3.65; 7.2] | 5.7 [4.6; 11.2] | 0.401 b | 4.95 [3.53; 6.83] | 5.7 [4.8; 12.6] | 0.138 b | |
CAP (v.n. < 237 dB/m) | 292 [242; 300] | 341 [289; 383] | 0.159 b | 310 [255;359] | 323 [273; 379] | 0.587 b | |
Steatosis and Fibrosis Liver Indices | |||||||
Fatty Liver Index (v.n. 0–100) | 88.6 [57.8; 96.3] | 97 [85.8; 99.3] | 0.042 b | 89.7 [55.2; 96.4] | 96.2 [86.5; 99.4] | 0.036 b | |
FIB-4 (n.v. < 3.25) | 0.60 [0.20–1.03] | 0.69 [0.17–1.89] | 0.207 b | 0.59 [0.73–1.89] | 0.73 [0.32–1.13] | 0.102 b | |
APRI (n.v. < 1) | 0.19 [0.14–0.23] | 0.23 [0.18–0.34] | 0.021 b | 0.19 [0.14–0.23] | 0.23 [0.18–0.32] | 0.027 b |
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de Alteriis, G.; Pugliese, G.; Di Sarno, A.; Muscogiuri, G.; Barrea, L.; Cossiga, V.; Perruolo, G.; Di Tolla, M.F.; Zumbolo, F.; Formisano, P.; et al. Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage. Int. J. Mol. Sci. 2023, 24, 10885. https://doi.org/10.3390/ijms241310885
de Alteriis G, Pugliese G, Di Sarno A, Muscogiuri G, Barrea L, Cossiga V, Perruolo G, Di Tolla MF, Zumbolo F, Formisano P, et al. Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage. International Journal of Molecular Sciences. 2023; 24(13):10885. https://doi.org/10.3390/ijms241310885
Chicago/Turabian Stylede Alteriis, Giulia, Gabriella Pugliese, Antonella Di Sarno, Giovanna Muscogiuri, Luigi Barrea, Valentina Cossiga, Giuseppe Perruolo, Michele Francesco Di Tolla, Francesca Zumbolo, Pietro Formisano, and et al. 2023. "Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage" International Journal of Molecular Sciences 24, no. 13: 10885. https://doi.org/10.3390/ijms241310885