Liver iron deposits in hepatitis B patients: Association with severity of liver disease but not with hemochromatosis gene mutations

Martinelli, A.L.C.; Filho, Antonio Balestrim; Franco, Rendrik F.; Tavella, Marli Haydee; Ramalho, Leandra Náira Zambelli; Zucoloto, Sérgio; Rodrigues, Sandra; Zago, M. A.

doi:10.1111/j.1440-1746.2004.03410.x

Cited by 61 publications

(59 citation statements)

References 37 publications

(109 reference statements)

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“…In contrast to C282Y mutation, H63D was more common in most of studies from India [5,8,18,19]. The overall allele frequency of H63D mutation was 5.26 (4.58 in controls and 5.95 in patients) which is quite similar to the previously reported studies by Panigrahi et al and Milman et al [17,20] but lesser than the others [8,13,25].…”

Section: Discussionsupporting

confidence: 82%

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

Jain

Agarwal

Tamhankar

et al. 2011

Indian J Gastroenterol

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Section: Discussionsupporting

confidence: 82%

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

Jain

Agarwal

Tamhankar

et al. 2011

Indian J Gastroenterol

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“…For example, high levels of serum ferritin and transferrin have been reported in these patients (13,33), although the causes of the increased serum ferritin and transferrin saturation remain unclear. Our observation that LHBsAg inhibited transferrin uptake by human hepatocytes provides a clue to the cause of the disordered metabolism of iron ions.…”

Section: Discussionmentioning

confidence: 99%

Entry of Hepatitis B Virus into Immortalized Human Primary Hepatocytes by Clathrin-Dependent Endocytosis

Huang

Chen

Chang

et al. 2012

J Virol

140

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The lack of a suitable in vitro hepatitis B virus (HBV) infectivity model has limited examination of the early stages of the virus-cell interaction. In this study, we used an immortalized cell line derived from human primary hepatocytes, HuS-E/2, to study the mechanism of HBV infection. HBV infection efficiency was markedly increased after dimethyl sulfoxide (DMSO)-induced differentiation of the cells. Transmission electron microscopy demonstrated the presence of intact HBV particles in DMSO-treated HBV-infected HuS-E/2 cells, which could be infected with HBV for up to at least 50 passages. The pre-S1 domain of the large HBsAg (LHBsAg) protein specifically interacted with clathrin heavy chain (CHC) and clathrin adaptor protein AP-2. Short hairpin RNA knockdown of CHC or AP-2 in HuS-E/2 cells significantly reduced their susceptibility to HBV, indicating that both are necessary for HBV infection. Furthermore, HBV entry was inhibited by chlorpromazine, an inhibitor of clathrin-mediated endocytosis. LHBsAg also interfered with the clathrin-mediated endocytosis of transferrin by human hepatocytes. This infection system using an immortalized human primary hepatocyte cell line will facilitate investigations into HBV entry and in devising therapeutic strategies for manipulating HBV-associated liver disorders.

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“…Yonal et al reported elevated serum transferrin saturation and ferritin concentration in patients with hepatitis B virus (HBV)-related liver disease [17]. Matinelli et al found elevated transferrin saturation in 27.1% of investigated HBV patients and increased liver iron deposition in 48.7% of the same cohort [18]. Hepcidin, a liver-produced peptide, is considered as the major control of body iron status.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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Liver iron deposits in hepatitis B patients: Association with severity of liver disease but not with hemochromatosis gene mutations

Abstract: Elevated TS and liver iron deposits were frequent in non-cirrhotic HBV patients. Iron deposits were mainly mild and associated with higher activity and severity of liver disease, but not with HFE mutations.

Cited by 61 publications

References 37 publications

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population

Entry of Hepatitis B Virus into Immortalized Human Primary Hepatocytes by Clathrin-Dependent Endocytosis

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

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