Low Serum Hepcidin is Associated with Reduced Short‐term Survival in Adults with Acute Liver Failure

Abstract

Background and Aims

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

Method

A representative subset of 121 ALF adults (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) vs. death/transplantation (NSS). Mice were assessed prior to (controls), four and 18 hours after injection of 300 mg/kg APAP

Results

ALF patients as well as APAP‐treated mice displayed increased ferritin, 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 ALFSG index (C‐statistic 0.87 vs. 0.85) and was better than MELD 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, and is an independent predictor and might be a useful component of future prognostic scores.

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