Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Sample Treatment
2.3. Statistics
3. Results
3.1. Clinical Outcomes
3.2. Multivariate Model and Feature Selection
3.3. Random Forest with Metabolites and Clinical Variables
3.4. Survival Analysis Based on Purines, Clinical Variables and Donation Groups
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Conflicts of Interest
References
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Donor | DBD (n = 35) | DCD (n = 12) | p-Value b | |
Age (years) | 53 (25–82) | 56 (35–76) | 0.526 | |
Gender (female/male) | 19/16 | 6/6 | 1 | |
Hepatic steatosis | No | 14 | 7 | |
Mild (<30%) | 18 | 3 | 0.305 | |
Moderate (30–60%) | 3 | 2 | ||
GGT (IU/L) a | 52 (6–208) | 92 (21–315) | 0.342 | |
AST (IU/L) a | 85 (22–517) | 161 (15–392) | 0.139 | |
ALT (IU/L) a | 72 (12–268) | 97 (13–201) | 0.623 | |
Bilirubin (μmoL/L) a | 11 (3–37) | 12 (4–26) | 0.695 | |
ITU stay (days) | 4 (1–28) | 4 (1–10) | 0.168 | |
Inotrop support (Y/N) | 19/16 | 6/6 | 1 | |
Functional WIT (min) | NA | 21 (9–33) | NA | |
CIT (min) | 504 (210–840) | 457 (270–720) | 0.212 | |
Recipient | DBD (n = 35) | DCD (n = 12) | p-Value b | |
Age (years) | 44 (20–65) | 54 (46–70) | 0.029 | |
Gender (female/male) | 13/22 | 5/7 | 1 | |
BMI (kg/m2) | 25.8 (18.4–34.6) | 27.3 (22.1–35.8) | 0.277 | |
MELD Score | 14.3 (2–34) | 10.7 (4–18) | 0.208 | |
UKELD Score | 53.3 (40–77) | 51.3 (44–61) | 0.571 | |
ALD | 9 | 3 | NA | |
PSC | 5 | 0 | ||
HCV | 1 | 2 | ||
HCC | 1 | 2 | ||
PHCC | 2 | 1 | ||
Others d | 17 | 4 | ||
AST (IU/L) a | 480 (10–7485) | 613 (18–5307) | 0.494 | |
Bilirubin day 7 (μmoL/L) | 56 (7–258) | 52 (12–103) | 0.772 | |
INR day 7 | 1.04 (0.85–1.21) | 1.06 (0.92–1.3) | 0.909 | |
EAD/EGF | 6/29 | 4/8 | 0.251 | |
Censored/Dead c | 22/3 | 7/2 | NA |
Indicators | AUC | Accuracy | Sensitivity | Specificity |
---|---|---|---|---|
adenine/urate + AMP/urate + hypoxanthine/urate + ALT | 0.84 | 0.68 | 0.65 | 0.80 |
adenine/urate + adenosine/urate + AMP/urate + hypoxanthine/urate | 0.80 | 0.70 | 0.65 | 0.90 |
AMP/urate | 0.75 | 0.66 | 0.62 | 0.80 |
GGT + bilirubin + AST + ALT + age + steatosis status | 0.71 | 0.57 | 0.57 | 0.60 |
adenine/urate | 0.70 | 0.64 | 0.60 | 0.80 |
hypoxanthine/urate | 0.68 | 0.53 | 0.51 | 0.60 |
bilirubin | 0.65 | 0.68 | 0.67 | 0.70 |
AST | 0.63 | 0.51 | 0.50 | 0.70 |
adenosine/urate | 0.62 | 0.53 | 0.49 | 0.70 |
ALT | 0.59 | 0.36 | 0.27 | 0.70 |
steatosis status | 0.55 | 0.49 | 0.46 | 0.60 |
age | 0.55 | 0.45 | 0.38 | 0.70 |
GGT | 0.47 | 0.79 | 1 | 0 |
Metabolites | AST | Bilirubin | GGT | |
---|---|---|---|---|
Adenine | Coefficient | −0.045 | −0.122 | −0.134 |
p-value | 0.968 | 0.321 | 0.275 | |
q-value | 0.968 | 0.482 | 0.825 | |
Adenosine | Coefficient | −0.005 | −0.274 | −0.084 |
p-value | 0.967 | 0.024 * | 0.496 | |
q-value | 0.967 | 0.072 | 0.744 | |
AMP | Coefficient | −0.009 | −0.097 | −0.106 |
p-value | 0.945 | 0.430 | 0.390 | |
q-value | 0.945 | 0.645 | 1 | |
Hypoxanthine | Coefficient | −0.189 | −0.320 | −0.039 |
p-value | 0.122 | 0.008 ** | 0.752 | |
q-value | 0.183 | 0.024 * | 0.752 | |
Urate | Coefficient | 0.042 | −0.019 | 0.204 |
p-value | 0.733 | 0.875 | 0.095 | |
q-value | 1 | 0.875 | 0.285 |
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Xu, J.; Hassan-Ally, M.; Casas-Ferreira, A.M.; Suvitaival, T.; Ma, Y.; Vilca-Melendez, H.; Rela, M.; Heaton, N.; Jassem, W.; Legido-Quigley, C. Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation. J. Clin. Med. 2020, 9, 711. https://doi.org/10.3390/jcm9030711
Xu J, Hassan-Ally M, Casas-Ferreira AM, Suvitaival T, Ma Y, Vilca-Melendez H, Rela M, Heaton N, Jassem W, Legido-Quigley C. Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation. Journal of Clinical Medicine. 2020; 9(3):711. https://doi.org/10.3390/jcm9030711
Chicago/Turabian StyleXu, Jin, Mohammad Hassan-Ally, Ana María Casas-Ferreira, Tommi Suvitaival, Yun Ma, Hector Vilca-Melendez, Mohamed Rela, Nigel Heaton, Wayel Jassem, and Cristina Legido-Quigley. 2020. "Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation" Journal of Clinical Medicine 9, no. 3: 711. https://doi.org/10.3390/jcm9030711