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Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan

Journal of Gastroenterology volume 42, pages 673–680 (2007)Cite this article

Abstract

Background

The clinical features of hepatitis C virus (HCV) carriers with persistently normal alanine aminotransferase (PNALT) levels (ALT ≤ 34 IU/l) have not been fully elucidated. We investigated clinical factors associated with ALT flare-up in PNALT individuals in a HCV hyperendemic area of Japan.

Methods

We analyzed 101 HCV carriers who had PNALT between 1993 and 2000. The first occurrence of ALT flare-up (ALT ≥ 35 IU/l) between 2001 and 2005 was evaluated by the Kaplan-Meier method. Multivariate analysis of factors predicting ALT flare-up were conducted using Cox proportional hazards models.

Results

The mean follow-up period was 2.8 years, and the 5-year cumulative incidence of ALT flare-up was estimated to be 31.8%. In multivariate analysis, an ALT level of 20–34 IU/l and a high serum ferritin level (≥90 ng/ml) in the most recently available data up to the year 2000, as well as H63D heterozygosity in the HFE gene, were independently and strongly associated with the incidence of ALT flare-up (Hazard ratios = 5.6, 3.1, and 4.8, respectively). In addition, HFE H63D heterozygosity was significantly associated with higher serum ferritin levels in subjects with PNALT (153.8 ± 73.3 ng/ml in subjects with the 63HD genotype vs. 89.4 ± 51.3 ng/ml in subjects with the 63HH genotype, P = 0.043).

Conclusions

HCV carriers with PNALT in this population were at risk for ALT flare-up. Basal ALT levels, serum ferritin levels, and HFE polymorphism are potentially important predictors of ALT flare-up.

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Affiliations

  1. Digestive Disease and Life-style related Disease, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-0056, Japan

    Hirofumi Uto, Akihiro Moriuchi, Susumu Hasegawa, Makoto Oketani & Hirohito Tsubouchi

  2. Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Kiyotake, Japan

    Joji Kurogi, Kazunori Kusumoto & Katsuhiro Hayashi

  3. Miyazaki Prefectural Industrial Support Foundation, Miyazaki, Japan

    Yuka Takahama

  4. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan

    Akio Ido & Hirohito Tsubouchi

  5. Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Michinori Kohara

  6. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Sherri O Stuver

  7. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Sherri O Stuver

Authors
  1. Hirofumi Uto
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  2. Joji Kurogi
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  3. Yuka Takahama
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  4. Kazunori Kusumoto
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  5. Katsuhiro Hayashi
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  6. Akio Ido
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  7. Michinori Kohara
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  8. Sherri O Stuver
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  9. Akihiro Moriuchi
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  10. Susumu Hasegawa
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  11. Makoto Oketani
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  12. Hirohito Tsubouchi
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Uto, H., Kurogi, J., Takahama, Y. et al. Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan. J Gastroenterol 42, 673–680 (2007). https://doi.org/10.1007/s00535-007-2078-0

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Key words

  • hepatitis C virus
  • persistent normal ALT
  • community-based population
  • ferritin
  • ALT flare-up