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Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596–0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

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Abbreviations

NASH:

Nonalcoholic steatohepatitis

NAFLD:

Nonalcoholic fatty liver disease

IR:

Insulin resistance

PCR:

Polymerase chain reaction

VFA:

Visceral fat area

BMI:

Body mass index

SFA:

Subcutaneous fat area

HOMA-IR:

Homeostasis model assessment for insulin resistance

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Acknowledgments

We thank Miss Machiko Hiraga for her technical support. This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan to A.N., a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KIBAN-B) to A.N., and a grant from the National Institute of Biomedical Innovation to A.N.

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Authors and Affiliations

  1. Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Yokohama, Kanazawa-ku, 236-0004, Japan

    Masato Yoneda, Yuichi Nozaki, Hiroki Endo, Hironori Mawatari, Hiroshi Iida, Koji Fujita, Kyoko Yoneda, Hirokazu Takahashi, Hiroyuki Kirikoshi, Masahiko Inamori, Noritoshi Kobayashi, Kensuke Kubota, Satoru Saito & Atsushi Nakajima

  2. Kitakashiwa Rehabilitation Hospital, 265 Kashiwashita, Kashiwa, Japan

    Shiro Maeyama

  3. Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro, Yokohama, Tsurumi-ku, Japan

    Kikuko Hotta

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  1. Masato Yoneda
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Correspondence to Atsushi Nakajima.

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Masato Yoneda and Yuichi Nozaki contributed equally to this work.

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Yoneda, M., Nozaki, Y., Endo, H. et al. Serum Ferritin Is a Clinical Biomarker in Japanese Patients with Nonalcoholic Steatohepatitis (NASH) Independent of HFE Gene Mutation. Dig Dis Sci 55, 808–814 (2010). https://doi.org/10.1007/s10620-009-0771-y

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