Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion

Fujita, Naoki; Sugimoto, Ryosuke; Motonishi, Satoshi; Tomosugi, Naohisa; Tanaka, Hideaki; Takasu, Masaki; Iwasa, Motoh; Kobayashi, Yoshinao; Hayashi, Hisao; Kaito, Masahiko; Takei, Yoshiyuki

doi:10.1016/j.jhep.2008.05.014

Cited by 82 publications

(84 citation statements)

References 27 publications

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“…Serum hepcidin-25 levels in our Japanese patients were relatively high at 30.7 ± 14.5 ng/mL compared to those in Italian HFE-hemochromatosis patients. Our findings, including the reduced hepcidin/ferritin ratio and correlation between hepcidin and ferritin concentrations fit well with reports showing that hepcidin induction was relatively impaired in CHC patients, but also that its regulation by iron stores was maintained (13,14). These findings are also in agreement with recent studies in animal and cellular models suggesting that HCV suppresses hepcidin production and may contribute to the development of iron overload in CHC (19,20).…”

Section: Discussionsupporting

confidence: 93%

“…The results of the current study did not differ from those in the literature. It is also important that the amount of body iron in CHC patients is considered a nontoxic level in healthy subjects because sensitivity to iron hepatotoxicity disappeared in complete responders to IFN without iron removal (13). However, the combination of even a slightly increased iron level with HCV-related insult may act synergistically to increase iron hepatotoxicity and the risk of progressive liver damage so that iron removal can be beneficial in this setting (3,4).…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of hepcidin regulation has been limited due to the lack of reliable methods. Recently serum hepcidin levels of CHC patients were measured in 2 studies using different methods (13,14). Both studies indicated that hepcidin regulation by iron stores is maintained in CHC and suggested that HCV infection can impair hepcidin production, which may be an important factor in hepatic iron accumulation.…”

Section: Introductionmentioning

confidence: 99%

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Patients with Chronic Hepatitis C May be More Sensitive to Iron Hepatotoxicity than Patients with HFE-Hemochromatosis

et al. 2010

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Aim In chronic hepatitis C, iron might play an important role as a hepatotoxic co-factor. Therefore, venesection, a standard treatment for hemochromatosis, has been proposed as an alternative for patients who respond poorly to anti-viral therapy. To improve our understanding of iron-induced hepatotoxicity, we compared the responses to venesection between patients with chronic hepatitis C and those with HFEhemochromatosis. Methods Fourteen Japanese patients with chronic hepatitis C and eight Italian patients with HFEhemochromatosis underwent repeated venesection with a serum ferritin endpoint of 20 and 50 ng/mL, respectively. Serum iron indices and liver function tests were measured in pre-and post treatment blood samples from each patient. Body iron stores were calculated using the removed blood volume. Results In both patients with hepatitis and hemochromatosis, serum ferritin, aminotransferase and hepcidin 25 were reduced after venesection. The serum aminotransferase activity, but not the serum ferritin level, was predictive of effective iron removal treatment. Hepcidin regulation was set at an inappropriately low level in hemochromatosis patients (11.1 ± 9.2 ng/mL), but not so in hepatitis patients (30.7 ± 14.5 ng/mL). Inversely, the estimated body iron stores of hemochromatosis patients were 5,960 ± 2,750 mg, while those of hepatitis patients were 730 ± 560 mg. Judging from the liver enzyme reduction ratio, patients with hepatitis seemed to be more sensitive to iron hepatotoxicity than hemochromatosis patients. Conclusion Even though the threshold of iron hepatotoxicity and benefit of its removal differ between patients with chronic hepatitis C and those with HFE-hemochromatosis, venesection is a valid choice of treatment to reduce liver disease activity in both diseases.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Patients with Chronic Hepatitis C May be More Sensitive to Iron Hepatotoxicity than Patients with HFE-Hemochromatosis

et al. 2010

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“…15,17,45,46 Three of our patients coinfected with HCV had a hepcidin-resistant iron overload syndrome without the evidence of a genetic basis for the latter.…”

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confidence: 86%

“…2,13,14 Evidence suggests that functional disruption of the hepcidin system might be a molecular basis for hemochromatosis, but few reports on the active form of serum hepcidin-25 have been published to date owing to the lack of reliable methods for quantitative determination. 15,16,17 Aceruloplasminemia is a neurological disorder characterized by heavy iron overload in the liver and brain with clinical manifestations of ataxia, involuntary movement, retinal degeneration, and dementia around the age of 50. 18 It results from a mutation in the ceruloplasmin gene (CP).…”

Section: Introductionmentioning

confidence: 99%

Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders

et al. 2010

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Background. Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes.Methods. We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography-tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE-hemochromatosis. Results.One patient with HJV-hemochromatosis, 2 with TFR2-hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes. Conclusion.Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis. (231 words)

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Microbial Disease Biomarkers Using ProteinChip Arrays

Hamilton

Levin

Kroll

et al. 2010

Mass Spectrometry for Microbial Proteomics

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Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion

Cited by 82 publications

References 27 publications

Patients with Chronic Hepatitis C May be More Sensitive to Iron Hepatotoxicity than Patients with HFE-Hemochromatosis

Patients with Chronic Hepatitis C May be More Sensitive to Iron Hepatotoxicity than Patients with HFE-Hemochromatosis

Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders

Microbial Disease Biomarkers Using ProteinChip Arrays

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