TY - JOUR
T1 - Low Serum Hepcidin Is Associated With Reduced Short-Term Survival in Adults With Acute Liver Failure
AU - for the Acute Liver Failure Study Group (ALFSG)
AU - Spivak, Igor
AU - Arora, Jyoti
AU - Meinzer, Caitlyn
AU - Durkalski-Mauldin, Valerie
AU - Lee, William M.
AU - Trautwein, Christian
AU - Fontana, Robert J.
AU - Strnad, Pavel
N1 - Funding Information:
Received May 28, 2018; accepted December 10, 2018. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.30486/suppinfo. Supported by the German Research Foundation grant STR 1095/4-1, IZKF research group funding, Else Kröner Exzellenzstipendium (to P.S.), SFB/TRR57 (to P.S. and C.T.), and NIH/NIDDK U-01 58369 to ALFSG. © 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30486 Potential conflict of interest: Dr. Lee consults for Sanofi, Novartis, Genentech, and Karuna. He received grants from Merck, Gilead, Conatus, Bristol-Myers Squibb, and Synlogic. Dr. Fontana consults for Alnylam and received grants from Bristol-Myers Squibb, Gilead, and AbbVie.
Publisher Copyright:
© 2018 by the American Association for the Study of Liver Diseases.
PY - 2019/5
Y1 - 2019/5
N2 - The liver has an important role in iron homeostasis through the synthesis of the serum transporter transferrin and the iron hormone hepcidin. The aim of this study was to analyze parameters of iron metabolism in a multicenter cohort of adult patients with acute liver failure (ALF) and in an acetaminophen (APAP)-induced ALF mouse model. A representative subset of 121 adults with ALF (including 66 APAP-related patients) had baseline serum samples tested for ferritin, transferrin, iron, and hepcidin. Outcomes at 3 weeks after enrollment were categorized as spontaneous survivor (SS) versus death/transplantation (NSS). Mice were assessed before (controls) and 4 and 18 hours after injection of 300 mg/kg APAP. Patients with ALF as well as APAP-treated mice displayed increased ferritin and diminished serum hepcidin and hepcidin/ferritin ratio. SS had lower iron (29.1% vs. 34.5 µmol/L; P < 0.05) and transferrin saturation (60.9% vs. 79.1%; P < 0.01), but higher hepcidin levels (8.2 vs. 2.7 ng/mL; P < 0.001) and hepcidin/ferritin ratio (0.0047 vs. 0.0009; P < 0.001) than NSS. In a multivariate analysis, a log-transformed hepcidin-containing model displayed similar prognostic power as the established Acute Liver Failure Study Group index (C-statistic 0.87 vs. 0.85) and was better than Model for End-Stage Liver Disease score (C-statistic 0.76). In mice, hepcidin levels inversely correlated with the surrogate of liver injury. Conclusion: Our findings demonstrate that several serum iron parameters significantly associate with 3-week outcomes in adults with ALF. Among them, hepcidin decreases early during experimental APAP-induced ALF, is an independent predictor and might be a useful component of future prognostic scores.
AB - The liver has an important role in iron homeostasis through the synthesis of the serum transporter transferrin and the iron hormone hepcidin. The aim of this study was to analyze parameters of iron metabolism in a multicenter cohort of adult patients with acute liver failure (ALF) and in an acetaminophen (APAP)-induced ALF mouse model. A representative subset of 121 adults with ALF (including 66 APAP-related patients) had baseline serum samples tested for ferritin, transferrin, iron, and hepcidin. Outcomes at 3 weeks after enrollment were categorized as spontaneous survivor (SS) versus death/transplantation (NSS). Mice were assessed before (controls) and 4 and 18 hours after injection of 300 mg/kg APAP. Patients with ALF as well as APAP-treated mice displayed increased ferritin and diminished serum hepcidin and hepcidin/ferritin ratio. SS had lower iron (29.1% vs. 34.5 µmol/L; P < 0.05) and transferrin saturation (60.9% vs. 79.1%; P < 0.01), but higher hepcidin levels (8.2 vs. 2.7 ng/mL; P < 0.001) and hepcidin/ferritin ratio (0.0047 vs. 0.0009; P < 0.001) than NSS. In a multivariate analysis, a log-transformed hepcidin-containing model displayed similar prognostic power as the established Acute Liver Failure Study Group index (C-statistic 0.87 vs. 0.85) and was better than Model for End-Stage Liver Disease score (C-statistic 0.76). In mice, hepcidin levels inversely correlated with the surrogate of liver injury. Conclusion: Our findings demonstrate that several serum iron parameters significantly associate with 3-week outcomes in adults with ALF. Among them, hepcidin decreases early during experimental APAP-induced ALF, is an independent predictor and might be a useful component of future prognostic scores.
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U2 - 10.1002/hep.30486
DO - 10.1002/hep.30486
M3 - Article
C2 - 30582749
AN - SCOPUS:85062966055
VL - 69
SP - 2136
EP - 2149
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 5
ER -