The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Selection
2.2. Variable Definitions
2.3. Statistical Methods
3. Results
3.1. Clinical Characteristics of Patients
3.2. Incidence of Voriconazole-Related Liver Injury
3.3. Disposal Cost of Voriconazole-Related Liver Injury
3.4. Predictors of Voriconazole-Related Liver Injury
3.5. Development and Validation of Nomogram
3.6. Yodon’s Index
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Total (n = 1372) | Groups | |||
---|---|---|---|---|---|
Derivation Set (n = 1035) | Validation Set (n = 337) | Statistical Value | p | ||
Basic information | |||||
Age (y) | 48.55 ± 17.14 | 48.19 ± 17.40 | 49.66 ± 16.29 | −1.410 a | 0.159 |
Male (n, %) | 939 (68.44) | 715 (69.08) | 224 (66.47) | 0.804 b | 0.370 |
Height (cm) | 164.82 ± 7.10 | 164.92 ± 7.14 | 164.52 ± 6.96 | 0.911 a | 0.363 |
Weight (kg) | 59.76 ± 10.99 | 58.89 ± 10.35 | 62.45 ± 12.39 | −4.761 a | <0.001 |
BMI (kg/m2) | 17.66 ± 3.51 | 17.93 ± 3.61 | 16.84 ± 3.04 | 5.437 a | <0.001 |
Fungal disease type (n, %) | |||||
Aspergillosis | 539 (39.29) | 443 (42.80) | 96 (28.49) | 21.842 b | <0.001 |
Cryptococcosis | 97 (7.07) | 80 (7.73) | 17 (5.04) | 2.789 b | 0.095 |
Candidiasis | 52 (3.79) | 35 (3.38) | 17 (5.04) | 1.928 b | 0.165 |
Talaromycosis | 4 (0.29) | 1 (0.10) | 3 (0.89) | 0.048 c | |
Unknown pathogen | 680 (49.56) | 476 (45.99) | 204 (60.53) | 128.199 b | <0.001 |
Major comorbidities (n, %) | |||||
Bacterial infection | 492 (35.86) | 402 (38.84) | 90 (26.71) | 16.275 b | <0.001 |
Chronic viral hepatitis B (normal liver biochemistry) | 91 (6.63) | 73 (7.05) | 18 (5.34) | 1.203 b | 0.273 |
Decompensated cirrhosis (normal liver biochemistry) | 60 (4.37) | 42 (4.06) | 18 (5.34) | 1.101 b | 0.317 |
Chronic renal failure | 213 (15.52) | 166 (16.04) | 47 (13.95) | 0.848 b | 0.357 |
Abnormal renal function | 41 (2.99) | 30 (2.90) | 11 (3.26) | 0.117 b | 0.732 |
Cancer | 246 (17.93) | 211 (20.39) | 35 (10.39) | 17.279 b | <0.001 |
Renal transplantation | 138 (10.06) | 120 (11.59) | 18 (5.34) | 10.988 b | 0.001 |
Stem cell transplantation | 75 (5.47) | 62 (5.99) | 13 (3.86) | 2.238 b | 0.135 |
Lung transplantation | 29 (2.11) | 23 (2.22) | 6 (1.78) | 0.240 b | 0.624 |
Liver transplantation | 5 (0.36) | 4 (0.39) | 1 (0.30) | 0.400 c | 1.000 |
Autoimmune disease | 93 (6.78) | 67 (6.47) | 26 (7.72) | 0.620 d | 0.431 |
Diabetes | 314 (22.89) | 227 (21.93) | 87 (25.82) | 2.173 b | 0.140 |
Chronic obstructive pulmonary disease | 51 (3.72) | 49 (4.73) | 2 (0.59) | 12.179 b | <0.001 |
Asthma | 22 (1.60) | 12 (1.16) | 10 (2.97) | 5.267 b | 0.022 |
Hypertension | 487 (35.50) | 337 (32.56) | 110 (32.64) | 0.001 b | 0.978 |
Heart disease | 166 (12.10) | 122 (11.79) | 44 (13.06) | 0.385 b | 0.535 |
Hyperlipidemia | 40 (2.92) | 28 (2.71) | 12 (3.56) | 0.657 b | 0.417 |
Anemia | 327 (23.83) | 226 (21.84) | 101 (29.97) | 9.267 b | 0.002 |
Hypoproteinemia | 340 (24.78) | 192 (18.55) | 148 (43.92) | 87.756 b | <0.001 |
Voriconazole dose (mg/kg) | 3.31 ± 0.51 | 3.34 ± 0.48 | 3.22 ± 0.58 | 3.573 a | <0.001 |
Voriconazole trough concentration (mg/L) | |||||
Cmin, M (P25, P75) | 2.66 (1.20,5.00) | 2.62 (1.25,5.16) | 2.62 (1.10,4.54) | 2.472 e | 0.013 |
Cmin < 1.0 mg/L (n, %) | 279 (20.34) | 227 (21.93) | 52 (15.43) | 6.634 b | 0.010 |
Cmin [1.0, 5.5] mg/L (n, %) | 797 (58.09) | 596 (57.58) | 201 (59.64) | 0.725 b | 0.394 |
Cmin > 5.5mg/L (n, %) | 296 (21.57) | 212 (20.48) | 84 (24.93) | 2.966 b | 0.085 |
Liver biochemical indicator | |||||
ALT [M(P25,P75), IU/L] | 22 (12,39) | 22 (12,39) | 23 (12,39) | 0.947 e | 0.344 |
AST [M(P25,P75), IU/L] | 24 (17,40) | 24 (17,40) | 24 (18,40) | 2.832 e | 0.005 |
TBil [M(P25,P75), μmol/L] | 7.7 (5.3,11.8) | 7.9 (5.4,12.1) | 7.4 (5.2,11.2) | 4.047 e | <0.001 |
DBil [M(P25,P75), μmol/L] | 3.5 (2.3,6.2) | 3.5 (2.3,6.3) | 3.4 (2.1,5.6) | 4.442 e | <0.001 |
ALP [M(P25,P75), IU/L] | 99 (72,144) | 99 (72,146) | 101 (72,138) | 5.553 e | <0.001 |
Group | n | Disposal Cost (Chinese Yuan) | ||
---|---|---|---|---|
Range | Mean | Median (P25, P75) | ||
non VCZ-LI | 1155 | 0.00~4823.43 | 58.19 | 0.00 (0.00, 0.00) |
VCZ-LI | 217 | 0.00~8372.65 | 599.23 | 101.90 (0.00, 786.48) |
General VCZ-LI | 175 | 0.00~4540.50 | 483.23 | 0.00 (0.00, 410.48) |
Severe VCZ-LI | 42 | 0.00~8372.65 | 1082.58 | 993.59 (361.70, 1451.76) |
Group | Discount Rate of 0% | Discount Rate of 8% | ||
---|---|---|---|---|
Mean | Median (P25, P75) | Mean | Median (P25, P75) | |
non VCZ-LI (n = 1155) | 46.06 | 0.00 (0.00, 0.00) | 66.64 | 0.00 (0.00, 0.00) |
VCZ-LI (n = 217) | 466.29 | 79.84 (0.00, 617.40) | 693.05 | 117.31 (0.00, 900.29) |
General VCZ-LI (n = 175) | 373.48 | 0.00 (0.00, 321.62) | 561.04 | 0.00 (0.00, 472.57) |
Severe VCZ-LI (n = 42) | 853.02 | 770.00 (294.08, 1124.14) | 1243.09 | 1128.31 (409.63, 1689.02) |
Variables | VCZ-LI Group (n = 152) | Non VCZ-LI Group (n = 883) | Statistical Value | p |
---|---|---|---|---|
Basic information | ||||
Age (y) | 49.55 ± 15.90 | 47.96 ± 17.64 | 1.117 a | 0.265 |
Male (n, %) | 99 (65.13) | 616 (69.76) | 1.302 b | 0.254 |
Height (㎝) | 164.25 ± 7.18 | 165.04 ± 7.14 | −1.255 a | 0.210 |
Weight (kg) | 58.54 ± 9.56 | 58.95 ± 10.48 | −0.445 a | 0.657 |
BMI (kg/m2) | 17.74 ± 3.43 | 17.96 ± 3.64 | −0.679 a | 0.497 |
Fungal disease (n, %) | ||||
Aspergillosis | 67 (44.08) | 376 (42.58) | 0.119 b | 0.730 |
Cryptococcosis | 4 (2.63) | 76 (8.61) | 6.492 b | 0.011 |
Candidiasis | 5 (3.29) | 30 (3.40) | 0.005 b | 0.946 |
Unknown pathogen | 76 (50.00) | 400 (45.30) | 1.153 b | 0.283 |
Major comorbidities (n, %) | ||||
Bacterial infection | 62 (40.79) | 340 (38.51) | 0.285 b | 0.594 |
Chronic viral hepatitis B (normal liver biochemistry) | 6 (3.95) | 67 (7.59) | 2.621 b | 0.105 |
Decompensated cirrhosis (normal liver biochemistry) | 10 (6.58) | 32 (3.62) | 2.908 b | 0.088 |
Chronic renal failure | 21 (13.82) | 145 (16.42) | 0.654 b | 0.419 |
Abnormal renal function | 4 (2.63) | 26 (2.94) | 0.045 b | 0.832 |
Cancer | 38 (25.00) | 173 (19.59) | 2.336 b | 0.126 |
Transplantation | 19 (12.50) | 190 (21.52) | 6.543 b | 0.011 |
Autoimmune disease | 12 (7.89) | 55 (6.23) | 0.594 b | 0.441 |
Diabetes | 32 (21.05) | 195 (22.08) | 0.081 b | 0.777 |
Chronic obstructive pulmonary disease or Asthma | 10 (6.58) | 51 (5.78) | 0.151 b | 0.698 |
Hypertension | 47 (30.92) | 330 (37.37) | 2.331 b | 0.127 |
Heart disease | 26 (17.11) | 96 (10.87) | 4.846 b | 0.028 |
Hyperlipidemia | 4 (2.63) | 24 (2.72) | 0.004 b | 0.952 |
Anemia | 41 (26.97) | 185 (20.95) | 2.756 b | 0.097 |
Hypoproteinemia | 47 (30.92) | 145 (16.42) | 18.044 b | <0.001 |
Voriconazole dose (mg/kg) | 3.36 ± 0.46 | 3.34 ± 0.48 | 0.448 a | 0.654 |
Cmin, [M (P25, P75), mg/L] | 4.96 (2.78, 7.46) | 2.33 (1.01, 4.34) | −8.317 c | <0.001 |
Predictors | β | S.E | Wald χ2 | p | OR | 95%CI |
---|---|---|---|---|---|---|
Cmin (mg/L) | 0.094 | 0.019 | 23.940 | <0.001 | 1.099 | (1.058, 1.140) |
hypoproteinemia | 0.544 | 0.217 | 6.275 | 0.012 | 1.723 | (1.126, 2.636) |
transplantation | −0.589 | 0.273 | 4.645 | 0.031 | 0.555 | (0.325, 0.948) |
Constant | −2.219 | 0.160 | 192.567 | <0.001 |
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Xiao, G.; Liu, Y.; Chen, Y.; He, Z.; Wen, Y.; Hu, M. The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China. J. Clin. Med. 2023, 12, 4254. https://doi.org/10.3390/jcm12134254
Xiao G, Liu Y, Chen Y, He Z, Wen Y, Hu M. The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China. Journal of Clinical Medicine. 2023; 12(13):4254. https://doi.org/10.3390/jcm12134254
Chicago/Turabian StyleXiao, Guirong, Yiyao Liu, Yanhua Chen, Zhiyao He, Yan Wen, and Ming Hu. 2023. "The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China" Journal of Clinical Medicine 12, no. 13: 4254. https://doi.org/10.3390/jcm12134254
APA StyleXiao, G., Liu, Y., Chen, Y., He, Z., Wen, Y., & Hu, M. (2023). The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China. Journal of Clinical Medicine, 12(13), 4254. https://doi.org/10.3390/jcm12134254