Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

Dong Lin,Jing Ding,Jian-Ying Liu,Jian Zhou,Zhi Dai,Wei-Zhong Cheng,Xin Wang,Yi-Feng He,Cai-Zhong Chen,Fanis Missirlis

doi:10.1371/journal.pone.0065551

Abstract

PurposeExcessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.MethodsSeventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.ResultsCirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.ConclusionsDecreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.

Highlights

Patients with hepatic cirrhosis exhibit a spectrum of neurologic complications, ranging from profound neurological dysfunction to mild neuropsychiatric deficits [1,2,3]
Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients
Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBVrelated cirrhotic patients

Summary

Introduction

Patients with hepatic cirrhosis exhibit a spectrum of neurologic complications, ranging from profound neurological dysfunction to mild neuropsychiatric deficits [1,2,3]. Burkhard et al found 21.6% patients exhibited definite Parkinsonism in a one-year follow-up study [4]. Jalan et al found about 67% cirrhotic patients showed evidence of cerebral dysfunction in neuropsychological tests [5]. Decreased essential substances for normal brain function, or increased toxic metabolites in the brain may underlie the pathogenesis of neurological complications in liver dysfunction. These toxic substances included ammonia, GABA, and heavy metals [1,8]

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