Biomarkers of Oncogenesis, Adipose Tissue Dysfunction and Systemic Inflammation for the Detection of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Measurement of Circulating Biomarkers
2.3. Statistical Analysis
3. Results
3.1. Patients’ Characteristics
3.2. Circulating Biomarkers Values in the Study Cohort
3.3. Diagnostic Accuracy of Circulating Biomarkers for HCC Detection
3.4. Predictors of HCC and Model Development
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Controls | HCC | p-Value |
---|---|---|---|
Patients, n | 119 | 72 | |
Age (years), median (IQR) | 58 (49–66) | 67 (62–70) | <0.001 |
Male gender, n (%) | 64 (54%) | 57 (79%) | <0.001 |
BMI (kg/m2), median (IQR) | 30.8 (28.0–34.0) | 30.4 (26.0–31.7) | 0.013 |
Obesity (BMI ≥ 30.0 kg/m2), n (%) | 72 (61%) | 39 (54%) | 0.450 |
T2DM, n (%) | 68 (57%) | 43 (60%) | 0.764 |
Dyslipidemia, n (%) * | 41 (57%) | 83 (69%) | 0.086 |
Hypertension, n (%) | 88 (74%) | 54 (75%) | 1.000 |
ALT (U/L), median (IQR) | 53 (31–72) | 34 (24–41) | <0.001 |
AST (U/L), median (IQR) | 41 (30–57) | 38 (30–50) | 0.280 |
γGT (U/L), median (IQR) | 63 (43–120) | 87 (57–179) | 0.023 |
Platelets (× 109/L), median (IQR) | 194 (161–239) | 132 (85–183) | <0.001 |
Albumin (g/dL), median (IQR) | 4.1 (3.8–4.4) | 3.9 (3.3–4.1) | <0.001 |
Total Bilirubin (mg/dL), median (IQR) | 0.8 (0.6–1.0) | 0.9 (0.7–1.5) | 0.001 |
INR, median (IQR) | 1.05 (1.00–1.11) | 1.14 (1.09–1.31) | <0.001 |
Total Cholesterol (mg/dL), median (IQR) | 175 (157–203) | 168 (139–181) | 0.025 |
HDL-Cholesterol (mg/dL), median (IQR) | 46 (39–59) | 44 (35–54) | 0.368 |
Triglycerides (mg/dL), median (IQR) | 124 (94–160) | 115 (84–132) | 0.009 |
Fasting Glucose (mg/dL), median (IQR) | 110 (92–129) | 112 (100–137) | 0.143 |
Cirrhosis, n (%) | 66 (55%) | 63 (88%) | <0.001 |
BCLC Stage (0/A/B/C/D), n | 7/40/15/7/3 | ||
HCC nodules (1/2/3/>3), n | 33/16/8/15 | ||
Size of major nodule (mm), median (IQR) | 18 (15–24) |
Biomarkers | Controls | HCC | p-Value |
---|---|---|---|
AFP (ng/mL), median IQR | 3.8 (2.7–5.1) | 6.0 (4.5–13.5) | <0.001 |
PIVKA-II (mAU/mL), median IQR | 33 (27–45) | 121 (54–1135) | <0.001 |
GPC-3 (pg/mL), median IQR | 35 (20–56) | 75 (40–104) | <0.001 |
Adiponectin (µg/mL), median IQR | 2.17 (1.35–3.30) | 4.95 (2.87–7.03) | <0.001 |
Leptin (ng/mL), median IQR | 20.6 (9.8–33.4) | 20.3 (13.2–34.9) | 0.649 |
IL-6 (pg/mL), median IQR | 3.1 (1.9–5.8) | 6.0 (4.1–12.5) | <0.001 |
Biomarker | AUC, 95%CI | Cut-off * | Se | Sp | +LR | −LR |
---|---|---|---|---|---|---|
AFP (ng/mL) | 0.763, 0.696–0.821 | >4.4 | 76.4 | 68.9 | 2.46 | 0.34 |
PIVKA-II (mAU/mL) | 0.853, 0.794–0.900 | >56 | 75.0 | 85.7 | 5.25 | 0.29 |
GPC-3 (pg/mL) | 0.759, 0.691–0.817 | >64 | 62.5 | 82.4 | 3.54 | 0.46 |
Adiponectin (µg/mL) | 0.770, 0.704–0.828 | >3.68 | 62.5 | 81.5 | 3.38 | 0.46 |
IL-6 (pg/mL) | 0.731, 0.662–0.792 | >3.6 | 79.2 | 62.2 | 2.09 | 0.34 |
Variables | OR, 95% CI | p-Value |
---|---|---|
Age (years) | 1.09 (1.02–1.16) | 0.007 |
Male gender | 11.95 (3.48–41.04) | <0.001 |
PIVKA-II (Log mAU/mL) | 6.87 (2.03–23.23) | 0.002 |
GPC-3 (Log pg/mL) | 15.63 (2.99–81.59) | 0.001 |
Adiponectin (µg/mL) | 1.54 (1.23–1.94) | <0.001 |
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Caviglia, G.P.; Armandi, A.; Rosso, C.; Gaia, S.; Aneli, S.; Rolle, E.; Abate, M.L.; Olivero, A.; Nicolosi, A.; Guariglia, M.; et al. Biomarkers of Oncogenesis, Adipose Tissue Dysfunction and Systemic Inflammation for the Detection of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Cancers 2021, 13, 2305. https://doi.org/10.3390/cancers13102305
Caviglia GP, Armandi A, Rosso C, Gaia S, Aneli S, Rolle E, Abate ML, Olivero A, Nicolosi A, Guariglia M, et al. Biomarkers of Oncogenesis, Adipose Tissue Dysfunction and Systemic Inflammation for the Detection of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Cancers. 2021; 13(10):2305. https://doi.org/10.3390/cancers13102305
Chicago/Turabian StyleCaviglia, Gian Paolo, Angelo Armandi, Chiara Rosso, Silvia Gaia, Serena Aneli, Emanuela Rolle, Maria Lorena Abate, Antonella Olivero, Aurora Nicolosi, Marta Guariglia, and et al. 2021. "Biomarkers of Oncogenesis, Adipose Tissue Dysfunction and Systemic Inflammation for the Detection of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease" Cancers 13, no. 10: 2305. https://doi.org/10.3390/cancers13102305