Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
Abstract
:1. Introduction
2. Results
2.1. Patients’ Characteristics
2.2. TLR4 Genotyping
2.3. TLR4 SNPs and HCC Occurrence
2.4. TLR4 SNPs and Secondary Endpoints
2.4.1. All-Cause and Liver-Related Deaths
2.4.2. Causes of Death in HCC Patients and Duration between HCC Diagnosis and All-Cause Death
2.4.3. Duration between HCC Diagnosis and Liver Related Death
2.4.4. Duration between Diagnosis of Cirrhosis and HCC Development or Death
3. Discussion
4. Materials and Methods
4.1. Inclusion Criteria and Definitions
4.2. TLR Genotyping
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AIH | autoimmune hepatitis |
ALP | alkaline phosphatase |
ALT | alanine aminotransferase |
ASH | alcoholic steatohepatitis |
AST | aspartate aminotransferase |
CTP | Child–Turcotte–Pugh |
gGT | gamma glutamyl-transferase |
HBV | hepatitis B virus |
HCV HR | hepatitis C virus hazard ratio |
INR | international normalized ratio |
MELD | model for end stage liver disease |
n | number |
NASH | non-alcoholic steatohepatitis |
PBC | primary biliary cholangitis |
SNP | single nucleotide polymorphism |
TLR4 | Toll-like receptor-4 |
HCC | hepatocellular carcinoma |
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Patient Characteristic | Value |
---|---|
Age in years, median (range) | 65 (25–78) |
Gender male, n (%) | 175 (67.3) |
AST (IU/mL), median (range) | 47 (29–75) |
ALT (IU/mL), median (range) | 32 (20–52) |
gGT (IU/mL), median (range) | 71 (38–156) |
ALP (IU/mL), median (range) | 116 (83–179) |
Total bilirubin (mg/dL), median (range) | 1.35 (0.86–2.94) |
INR median (range) | 1.34 (1.2–1.6) |
MELD score, median (range) | 12 (9–18) |
CTP score, median (range) | 7 (6–9) |
CTP staging (A/B/C), n (%) | 105/96/59, (40.4/37/22.6) |
HBV-induced cirrhosis, n (%) | 40 (15.4) |
HCV-induced cirrhosis, n (%) | 49 (18.9) |
NASH-induced cirrhosis, n (%) | 34 (13.1) |
ASH-induced cirrhosis, n (%) | 83 (31.9) |
PBC-induced cirrhosis, n (%) | 17 (6.5) |
AIH-induced cirrhosis, n (%) | 8 (3.1) |
PBC/AIH-induced cirrhosis, n (%) | 7 (2.7) |
Cryptogenic cirrhosis, n (%) | 10 (3.8) |
TLR4 299 heterozygous/homozygous SNP, n (%) | 49/13, (18.9/5.0) |
TLR4 399 SNP heterozygous/homozygous SNP, n (%) | 8/0 (3.1/0) |
Univariable Analysis | Multivariable Analysis | |||
---|---|---|---|---|
Variable | OR (95% CI) | p Value | OR (95% CI) | p Value |
Age | 1.03 (1–1.05) | 0.0692 | 1.03 (1–1.07) | 0.0348 |
Gender (Male) | 2.4 (1.12–4.99) | 0.0234 | 2.7 (1.07–6.83) | 0.0358 |
NASH | 1.64 (0.38–7.11) | 0.3204 | 1.44 (0.31–6.78) | 0.5915 |
Alcohol | 1.08 (0.28–4.22) | 0.8873 | 0.9 (0.21–3.87) | 0.468 |
Viral | 1.88 (0.5–7.03) | 0.0653 | 1.88 (0.46–7.66) | 0.1137 |
Autoimmune | 0.55 (0.1–3.06) | 0.1624 | 0.88 (0.13–5.89) | 0.6357 |
MELD | 1.01 (0.98–1.05) | 0.4620 | 1 (0.93–1.07) | 0.8892 |
CTP | 1.07 (0.95–1.21) | 0.2761 | 1.13 (0.89–1.43) | 0.3137 |
TLR4 Mutations (both) | 0.6 (0.3–1.31) | 0.2071 | 0.08 (0–3.2) | 0.1812 |
TLR4 299 Mutation (any) | 0.5 (0.23–1.17) | 0.1141 | 5.29 (0.15–183.4) | 0.3575 |
TLR4 399 Mutation (any) | 2.4 (0.6–10.7) | 0.2231 | 17.7 (0.76–414.14) | 0.0741 |
Univariate Analysis | Multivariate Analysis | |||
---|---|---|---|---|
Parameter | Hazard Ratio | p Value | Hazard Ratio | p Value |
TLR4 mutation | 0.802 | 0.2690 | 0.717 | 0.1374 |
MELD | 1.008 | 0.3694 | 0.993 | 0.6746 |
CTP | 1.024 | 0.5024 | 1.078 | 0.2582 |
HCC | 1.382 | 0.0936 | 1.314 | 0.1832 |
Age | 1.007 | 0.3044 | 1.004 | 0.5434 |
Gender (female) | 0.647 | 0.0276 | 0.555 | 0.0251 |
Cause of cirrhosis | ||||
NASH | 0.768 | 0.2275 | 0.645 | 0.4233 |
Alcohol | 0.905 | 0.6224 | 0.437 | 0.1067 |
Viral | 1.287 | 0.1851 | 0.441 | 0.1125 |
Autoimmune | 1.096 | 0.7273 | 0.712 | 0.5662 |
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Androutsakos, T.; Bakasis, A.-D.; Pouliakis, A.; Gazouli, M.; Vallilas, C.; Hatzis, G. Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study. Int. J. Mol. Sci. 2022, 23, 9430. https://doi.org/10.3390/ijms23169430
Androutsakos T, Bakasis A-D, Pouliakis A, Gazouli M, Vallilas C, Hatzis G. Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study. International Journal of Molecular Sciences. 2022; 23(16):9430. https://doi.org/10.3390/ijms23169430
Chicago/Turabian StyleAndroutsakos, Theodoros, Athanasios-Dimitrios Bakasis, Abraham Pouliakis, Maria Gazouli, Christos Vallilas, and Gregorios Hatzis. 2022. "Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study" International Journal of Molecular Sciences 23, no. 16: 9430. https://doi.org/10.3390/ijms23169430