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• W3145909690 abstract "We read with interest the article by Agopian et al. entitled: “Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction”.[1]Agopian V.G. Markovic D. Klintmalm G.B. Saracino G. Chapman W.C. Vachharajani N. et al.Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.J Hepatol. 2021; 74: 881-892Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Because early liver allograft dysfunction is difficult to assess, L-GrAFT emerges as a promising tool to detect such dysfunction. We look forward to using this kinetic approach to assess early allograft function in future research but encountered discrepancies in the publications. The formula for L-GrAFT10 is provided as follows[1]Agopian V.G. Markovic D. Klintmalm G.B. Saracino G. Chapman W.C. Vachharajani N. et al.Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.J Hepatol. 2021; 74: 881-892Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar: Risk Score = 9.77 - 0.429 ∗ (AUC log AST) + 0.005 ∗ (AUC log AST squared) + 4.607 ∗ (early slope log AST) + 4.413 ∗ (early slope log AST squared) + 0.890 ∗ (log max INR) - 0.049 ∗ (AUC log TBIL) + 0.004 ∗ (AUC log TBIL squared) + 5.336 ∗ (slope log TBIL) - 0.046∗ (AUC log PLT) -5.249 ∗ (slope log PLT) + 13.086 ∗ (slope log PLT squared). We found this formula to provide drastically different risk estimates than the calculator provided in the article’s supplement. The error arises from the calculator using all 14 decimals of the odds ratios’ natural logarithms, while these coefficients (bolded) are rounded down to 3 decimals in the formula given in the article. The underlying problem is the uniform rounding of coefficients to 3 decimals when these are used to multiply variables that have quantities of different orders of magnitude. For instance, rounding to the third decimal the coefficient for a variable with values <1 (e.g. log max INR) leads to an error <0.001, whereas the same rounding for a variable with values >1,000 makes an order 1 error. We presume that unrounded coefficients were used in creating L-GrAFT10. However, using uniformly rounded factors in the formula can yield very different risk estimates; risk scores can vary from -2.39 to -1.17, which translates to a difference in individual risk estimates from 8.4% to 23.7% just from the effect of erroneous rounding of coefficients (Table 1). There might also exist an error in the calculator, since L-GrAFT7 is calculated using rounded coefficients in the article’s supplemental calculator.Table 1An example of the impact of rounding of coefficients on risk estimates using the unrounded (L-GrAFT10 calculator provided in the supplement of the Agopian et al. study[1]Agopian V.G. Markovic D. Klintmalm G.B. Saracino G. Chapman W.C. Vachharajani N. et al.Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.J Hepatol. 2021; 74: 881-892Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar) and rounded coefficients.PredictorLog ORORVariable valueLog OR roundedIntercept9.77AUC log AST-0.4294591770.65086151.73551342-0.429AUC log AST, squared0.0046213051.0046322676.5633480.005Slope log AST (early)4.607190144100.2022-0.2054680624.607Slope log AST (early), squared4.41290034982.508420.0422171254.413Log max INR0.8897397542.4344960.4054651080.890AUC log TBIL-0.048521140.952637222.36992196-0.049AUC log TBIL, squared0.003625421.003632500.41340840.004Slope log TBIL5.336266599207.7357-0.0100947965.336AUC log PLT-0.0462053130.954845944.91034035-0.046Slope log PLT-5.2489749740.00525290.171097045-5.249Slope log PLT squared13.08633488482306.40.02927419913.086L-GrAFT10-2.39With rounded factors:-1.17Odds ->0.090.31Individualized risk8.36%23.68%AST, aspartate aminotransferase; AUC, area under curve calculated as 10-day mean ∗ 10; early slope, slope of linear regression of values in first 7 days post-transplant; INR, international normalized ratio; OR, odds ratio; PLT, platelets; TBIL, total bilirubin. Open table in a new tab AST, aspartate aminotransferase; AUC, area under curve calculated as 10-day mean ∗ 10; early slope, slope of linear regression of values in first 7 days post-transplant; INR, international normalized ratio; OR, odds ratio; PLT, platelets; TBIL, total bilirubin. In addition, we found no explanation for changing the constant term in the formula from 11.27 in the original publication[2]Agopian V.G. Harlander-Locke M.P. Markovic D. Dumronggittigule W. Xia V. Kaldas F.M. et al.Evaluation of early allograft function using the liver graft assessment following transplantation risk score model.JAMA Surg. 2018 May 1; 153: 436-444Crossref PubMed Scopus (52) Google Scholar to 9.77 in the validation study.[1]Agopian V.G. Markovic D. Klintmalm G.B. Saracino G. Chapman W.C. Vachharajani N. et al.Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.J Hepatol. 2021; 74: 881-892Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Unfortunately, the website lgraft.com mentioned in the article is not yet in operation. As definitions of early liver allograft dysfunction are increasingly important for both clinical practice and research, an unequivocal formula to calculate L-GrAFT is needed in order to avoid severe misinterpretations. The authors received no financial support to produce this manuscript. All authors contributed to the design and writing of this paper. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following is the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1 Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunctionJournal of HepatologyVol. 74Issue 4PreviewEarly allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT7) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF. Full-Text PDF Reply to: correspondence regarding “Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction”Journal of HepatologyVol. 75Issue 3PreviewWe greatly appreciate the comments of Professor Avolio and colleagues1 and Professor Eerola and colleagues2 in response to our international, multicenter validation of the L-GrAFT score3 as a measure of early allograft dysfunction following LT. Eerola and colleagues have raised the extremely important issue of having an unequivocal formula for the calculation of L-GrAFT, as rounding of the coefficients to 3 decimal points, particularly for the squared terms, may dramatically alter the calculated risk score. Full-Text PDF" @default.
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• W3145909690 title "An unequivocal formula to calculate L-GrAFT score is needed" @default.
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