TY - JOUR
T1 - Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis
AU - Atkinson, Stephen R.
AU - Hamesch, Karim
AU - Spivak, Igor
AU - Guldiken, Nurdan
AU - Cabezas, Joaquín
AU - Argemi, Josepmaria
AU - Theurl, Igor
AU - Zoller, Heinz
AU - Cao, Sheng
AU - Mathurin, Philippe
AU - Shah, Vijay H.
AU - Trautwein, Christian
AU - Bataller, Ramon
AU - Thursz, Mark R.
AU - Strnad, Pavel
N1 - Funding Information:
Guarantor of the article: Pavel Strnad, MD. Specific author contributions: Stephen R. Atkinson, MD, Karim Hamesch, MD, Mark R. Thursz, MD, and Pavel Strnad, MD contributed equally to this work. Study concept and design: S.R.A., K.H., M.R.T., and P.S. Acquisition of data: S.R.A., K.H., I.S., N.G., J.C., J.A., I.T., H.Z., S.C., P.M., V.H.S. C.T., R.B., M.R.T., and P.S. Analysis and interpretation of data: S.R.A., K.H., J.A., and P.S. Drafting of the manuscript: S.R.A., K.H., and P.S. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: S.R.A. and K.H. Figures and tables: S.R.A., K.H., and P.S. Obtained funding: S.R.A., K.H., R.B., M.R.T., and P.S. Study supervision: S.R.A., K.H., M.R.T., and P.S. All authors had full access to all of the data and approved the final version of this manuscript. All authors can take responsibility for the integrity of the data and the accuracy of the data analysis. Financial support: This work was supported by the Interdisciplinary Center for Clinical Research (IZKF) within the faculty of Medicine at the RWTH Aachen University (to P.S.), by the Deutsche Forschungsgemeinschaft (DFG) SFB/TRR57 (to P.S. and C.T.), the Else Kröner Excellence Fellowship (to P.S.), the German Liver Foundation (to K.H.), the START program within the medical faculty at RWTH Aachen University (to K.H.), the Medical Research Council (to S.R.A. and M.R.T.), and the National Institute for Health Research (to M.R.T.). S.R.A. and M.R.T. acknowledge the support of the NIHR Imperial Biomedical Research Centre. R.B. is supported by NIH/NIAAA grants AA026972, AA026978 and AA026264, and by NIH/NIDDK grant P30DK120531. J.C. received the Juan Rodés Scholarship 2015 supported by AEEH (Asociación Española para el Estudio del Hígado—Spanish Association for the Study of Liver Diseases). Potential competing interests: All authors declare no support from any organization other than the below mentioned ones for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work. Hence, all authors declare themselves to be independent from funders with respect to this manuscript. Further remarks: We attest that we did not use any copyright protected material in our manuscript. No writing assistance was provided.
Publisher Copyright:
© 2020 Wolters Kluwer Health. All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - OBJECTIVES:Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH.METHODS:Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628).RESULTS:Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively).DISCUSSION:In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.
AB - OBJECTIVES:Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH.METHODS:Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628).RESULTS:Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively).DISCUSSION:In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.
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U2 - 10.14309/ajg.0000000000000492
DO - 10.14309/ajg.0000000000000492
M3 - Article
C2 - 31985531
AN - SCOPUS:85081945368
SN - 0002-9270
VL - 115
SP - 398
EP - 405
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 3
ER -