Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection
Abstract
:1. Introduction
2. Results
2.1. Association of Ceramide Species Levels with Gender, Fatty Liver, Diabetes, Age, and Body Mass Index in HCV Patients
2.2. Ceramide Species Levels and the Model for End-Stage Liver Disease Score in HCV Patients before DAA Therapy
2.3. Ceramide Species Levels and MELD Score in HCV Patients at 12 Weeks after the Start of Therapy
2.4. Ceramide Species Levels and Non-Invasive Scores of Liver Fibrosis/Cirrhosis in HCV Patients
2.5. Ceramide Species Levels and MELD Score in HCV Patients with and without Liver Cirrhosis
2.6. Impact of DAA Therapy on Serum LDL and Ceramide Levels
2.7. Very-Long-Chain to Long-Chain Ceramides in HCV Patients before Therapy and at 12 Weeks after Start of Treatment
2.8. Association of Ceramide Species Levels with Viral Load and Genotype in Non-Cirrhosis HCV Patients
3. Discussion
4. Materials and Methods
4.1. Study Cohort
4.2. Lipid Extraction and Analysis of Ceramide Species
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
References
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Laboratory Parameter | Baseline (178 Patients) | 12 Weeks Therapy (176 Patients) | p-Value |
---|---|---|---|
Age, years | 54 (24–82) | 54 (24–82) | ns |
BMI, kg/m2 | 25.6 (17.6–41.6) | 25.6 (17.6–41.6) | ns |
MELD | 7 (6–21) | 7 (6–21) | ns |
Platelets, n/nL | 195 (38–402) | 206 (37–407) | ns |
Ferritin, ng/mL | 128.6 (5.6–2309) | 94.2 (2.9–1161) | 0.003 |
ALT, U/L | 61 (2–305) | 26 (6–388) | <0.001 |
AST, U/L | 47 (7–1230) | 22 (6–836) | <0.001 |
Bilirubin, mg/dL | 1.0 (1.0–4.3) | 1.0 (1.0–7.5) | ns |
Albumin, g/L | 38 (2–50) | 39 (16–93) | ns |
INR | 1.05 (1.00–2.44) | 1.04 (1.00–2.22) | ns |
Creatinine, mg/dL | 0.78 (0.14–14.00) | 0.76 (0.14–14.7) | ns |
Leukocytes, n/L | 6.5 (2.2–72.4) | 6.8 (2.4–62.9) | ns |
CRP, mg/L | 2.9 (1.0–55.0) | 2.9 (2.9–20.3) | ns |
HDL, mg/dL | 52 (19–111) | 50 (13–96) | ns |
LDL, mg/dL | 95 (23–296) | 119 (33–251) | <0.001 |
Ceramide Species d18:1;O2/nmol/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|
Variables | 16:0 | 18:0 | 20:0 | 22:0 | 23:0 | 24:0 | 24:1 | 26:0 | |
BMI, kg/m2 | r | 0.079 | −0.052 | 0.032 | 0.118 | 0.121 | 0.023 | 0.013 | −0.101 |
p | - | - | - | - | - | - | - | - | |
Age, years | r | 0.200 | 0.062 | 0.017 | −0.136 | −0.012 | −0.239 | −0.012 | −0.022 |
p | - | - | - | - | - | 0.011 | - | - | |
MELD score | r | 0.124 | −0.317 | −0.346 | −0.380 | −0.298 | −0.461 | −0.295 | −0.205 |
p | - | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.049 | |
ALT, U/L | r | 0.117 | −0.191 | −0.226 | −0.286 | −0.247 | −0.352 | −0.176 | −0.165 |
p | - | - | 0.019 | <0.001 | 0.007 | <0.001 | - | - | |
AST, U/L | r | 0.005 | −0.156 | −0.118 | −0.164 | −0.143 | −0.151 | −0.117 | −0.115 |
p | - | - | - | - | - | - | - | - | |
Bilirubin, mg/dL | r | 0.085 | −0.213 | −0.255 | −0.257 | −0.240 | −0.322 | −0.208 | −0.111 |
p | - | 0.034 | 0.005 | 0.004 | 0.010 | <0.001 | 0.043 | - | |
Albumin, g/L | r | −0.133 | 0.248 | 0.279 | 0.309 | 0.228 | 0.368 | 0.200 | 0.212 |
p | - | 0.008 | 0.002 | <0.001 | 0.021 | <0.001 | - | 0.041 | |
INR | r | 0.174 | −0.289 | −0.320 | −0.395 | −0.336 | −0.496 | −0.308 | −0.237 |
p | - | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.011 | |
Creatinine, mg/dL | r | −0.069 | −0.039 | −0.093 | −0.078 | 0.002 | −0.046 | −0.009 | 0.053 |
p | - | - | - | - | - | - | - | - | |
Leukocytes, n/L | r | −0.066 | 0.201 | 0.237 | 0.121 | 0.127 | 0.201 | 0.255 | 0.090 |
p | - | - | 0.011 | - | - | - | 0.004 | - | |
Platelets, n/nL | r | −0.215 | 0.249 | 0.274 | 0.249 | 0.222 | 0.397 | 0.272 | 0.253 |
p | 0.031 | 0.006 | 0.002 | 0.007 | 0.023 | <0.001 | 0.002 | 0.005 | |
CRP, mg/L | r | 0.233 | 0.100 | 0.147 | 0.076 | 0.064 | 0.053 | 0.177 | 0.088 |
p | 0.014 | - | - | - | - | - | - | - | |
Ferritin, ng/mL | r | 0.053 | 0.029 | 0.049 | 0.030 | 0.023 | −0.056 | 0.097 | −0.028 |
p | - | - | - | - | - | - | - | - | |
Viral load | r | −0.069 | 0.131 | 0.208 | 0.158 | 0.144 | 0.114 | 0.064 | −0.009 |
p | - | - | 0.043 | - | - | - | - | - | |
HDL, mg/dL | r | 0.033 | 0.110 | 0.059 | 0.077 | 0.094 | 0.131 | 0.044 | 0.136 |
p | - | - | - | - | - | - | - | - | |
LDL, mg/dL | r | 0.291 | 0.310 | 0.517 | 0.614 | 0.624 | 0.666 | 0.578 | 0.383 |
p | 0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Ceramide Species d18:1;O2/nmol/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|
Variables | 16:0 | 18:0 | 20:0 | 22:0 | 23:0 | 24:0 | 24:1 | 26:0 | |
BMI, kg/m2 | r | 0.055 | 0.037 | 0.101 | 0.196 | 0.167 | 0.067 | 0.027 | −0.092 |
p | - | - | - | - | - | - | - | - | |
Age, years | r | 0.252 | 0.183 | 0.187 | 0.025 | 0.152 | −0.103 | 0.147 | 0.063 |
p | 0.023 | - | - | - | - | - | - | - | |
MELD score | r | 0.043 | −0.150 | −0.101 | −0.191 | −0.116 | −0.230 | −0.130 | −0.080 |
p | - | - | - | - | - | - | - | - | |
ALT, U/L | r | 0.082 | −0.148 | −0.168 | −0.205 | −0.173 | −0.194 | −0.137 | −0.134 |
p | - | - | - | - | - | - | - | - | |
AST, U/L | r | −0.003 | −0.105 | −0.119 | −0.168 | −0.127 | −0.234 | −0.077 | −0.119 |
p | - | - | - | - | - | 0.046 | - | - | |
Bilirubin, mg/dL | r | −0.026 | −0.058 | −0.076 | −0.046 | −0.022 | −0.024 | −0.004 | 0.015 |
p | - | - | - | - | - | - | - | - | |
Albumin, g/L | r | −0.069 | 0.115 | 0.027 | 0.082 | 0.007 | 0.123 | 0.018 | 0.067 |
p | - | - | - | - | - | - | - | - | |
INR | r | 0.104 | −0.140 | −0.072 | −0.219 | −0.148 | −0.286 | −0.145 | −0.127 |
p | - | - | - | - | - | 0.005 | - | - | |
Creatinine, mg/dL | r | −0.040 | −0.031 | −0.041 | 0.009 | 0.041 | 0.019 | 0.031 | 0.106 |
p | - | - | - | - | - | - | - | - | |
Leukocytes, n/L | r | −0.008 | 0.152 | 0.127 | −0.019 | −0.044 | 0.001 | 0.140 | −0.072 |
p | - | - | - | - | - | - | - | - | |
Platelets, n/nL | r | −0.196 | 0.124 | 0.052 | 0.041 | 0.012 | 0.156 | 0.101 | 0.119 |
p | - | - | - | - | - | - | - | - | |
CRP, mg/L | r | 0.260 | 0.136 | 0.160 | 0.128 | 0.082 | 0.139 | 0.258 | 0.150 |
p | 0.017 | - | - | - | - | - | 0.018 | ||
Ferritin, ng/mL | r | 0.034 | −0.017 | −0.010 | −0.023 | 0.001 | −0.093 | 0.037 | 0.001 |
p | - | - | - | - | - | - | - | - | |
Viral load | r | −0.031 | 0.064 | 0.134 | 0.100 | 0.115 | 0.009 | 0.028 | −0.010 |
p | - | - | - | - | - | - | - | - | |
HDL, mg/dL | r | −0.043 | 0.055 | −0.061 | −0.030 | 0.006 | 0.059 | −0.062 | 0.107 |
p | - | - | - | - | - | - | - | - | |
LDL, mg/dL | r | 0.407 | 0.290 | 0.499 | 0.598 | 0.584 | 0.605 | 0.539 | 0.413 |
p | <0.001 | 0.007 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Ceramide Species d18:1;O2/nmol/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|
Variables | 16:0 | 18:0 | 20:0 | 22:0 | 23:0 | 24:0 | 24:1 | 26:0 | |
BMI, kg/m2 | r | 0.073 | −0.159 | −0.031 | 0.167 | 0.181 | 0.202 | 0.113 | −0.022 |
p | - | - | - | - | - | - | - | - | |
Age, years | r | −0.218 | 0.083 | 0.084 | −0.172 | −0.149 | −0.168 | −0.081 | 0.003 |
p | - | - | - | - | - | - | - | - | |
MELD score | r | 0.032 | −0.326 | −0.390 | −0.257 | −0.287 | −0.392 | −0.345 | −0.294 |
p | - | - | - | - | - | - | - | - | |
ALT, U/L | r | 0.017 | −0.225 | 0.111 | −0.017 | 0.006 | −0.006 | −0.015 | −0.008 |
p | - | - | - | - | - | - | - | - | |
AST, U/L | r | 0.019 | −0.209 | <0.001 | −0.242 | −0.242 | −0.271 | −0.109 | −0.039 |
p | - | - | - | - | - | - | - | - | |
Bilirubin, mg/dL | r | 0.066 | −0.194 | −0.172 | −0.251 | −0.308 | −0.372 | −0.240 | −0.146 |
p | - | - | - | - | - | - | - | - | |
Albumin, g/L | r | 0.040 | 0.281 | 0.380 | 0.427 | 0.454 | 0.531 | 0.309 | 0.347 |
p | - | - | - | 0.048 | 0.026 | 0.003 | - | - | |
INR | r | −0.008 | −0.350 | −0.491 | −0.384 | −0.495 | −0.586 | −0.480 | −0.352 |
p | - | - | 0.010 | - | 0.009 | 0.001 | 0.014 | - | |
Creatinine, mg/dL | r | −0.231 | 0.030 | −0.078 | −0.101 | 0.079 | −0.007 | 0.018 | 0.072 |
p | - | - | - | - | - | - | - | - | |
Leukocytes, n/L | r | −0.043 | −0.009 | 0.176 | 0.177 | 0.357 | 0.402 | 0.297 | 0.436 |
p | - | - | - | - | - | - | - | 0.040 | |
Platelets, n/nL | r | −0.119 | −0.074 | 0.241 | 0.214 | 0.367 | 0.443 | 0.238 | 0.445 |
p | - | - | - | - | - | 0.034 | - | 0.032 | |
CRP, mg/L | r | 0.163 | 0.194 | 0.258 | 0.124 | 0.106 | 0.057 | 0.169 | −0.019 |
p | - | - | - | - | - | - | - | - | |
Ferritin, ng/mL | r | 0.176 | 0.102 | 0.283 | 0.226 | 0.147 | 0.105 | 0.367 | −0.140 |
p | - | - | - | - | - | - | - | - | |
Viral load | r | −0.083 | 0.049 | −0.006 | −0.064 | −0.072 | −0.021 | −0.150 | −0.196 |
p | - | - | - | - | - | - | - | - | |
HDL, mg/dL | r | 0.433 | 0.243 | 0.391 | 0.340 | 0.286 | 0.301 | 0.279 | 0.122 |
p | - | - | - | - | - | - | - | - | |
LDL, mg/dL | r | 0.414 | 0.384 | 0.430 | 0.615 | 0.654 | 0.674 | 0.588 | 0.191 |
p | - | - | 0.042 | <0.001 | <0.001 | <0.001 | 0.001 | - |
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Höring, M.; Peschel, G.; Grimm, J.; Krautbauer, S.; Müller, M.; Weigand, K.; Liebisch, G.; Buechler, C. Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection. Int. J. Mol. Sci. 2022, 23, 9806. https://doi.org/10.3390/ijms23179806
Höring M, Peschel G, Grimm J, Krautbauer S, Müller M, Weigand K, Liebisch G, Buechler C. Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection. International Journal of Molecular Sciences. 2022; 23(17):9806. https://doi.org/10.3390/ijms23179806
Chicago/Turabian StyleHöring, Marcus, Georg Peschel, Jonathan Grimm, Sabrina Krautbauer, Martina Müller, Kilian Weigand, Gerhard Liebisch, and Christa Buechler. 2022. "Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection" International Journal of Molecular Sciences 23, no. 17: 9806. https://doi.org/10.3390/ijms23179806