Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection

Kawamura, Yusuke; Akuta, Norio; Sezaki, Hitomi; Hosaka, Tetsuya; Someya, Takashi; Kobayashi, Masahiro; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

doi:10.1007/s00535-005-1636-6

Cited by 28 publications

(21 citation statements)

References 24 publications

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“…Therefore, the present study is in accordance with the literature as it also shows a positive correlation between iron status and liver function markers. Moreover, there are reports which show that in patients with CHC iron depletion by phlebotomy was associated with clinical improvement assessed by significant reduction in liver function markers and iron status prior to [28] and after [29] treatment with interferon a.…”

Section: Discussionmentioning

confidence: 96%

Increased Oxidative Stress, Decreased Total Antioxidant Capacity, and Iron Overload in Untreated Patients with Chronic Hepatitis C

et al. 2009

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The aim of this study was to determine oxidative stress in patients with untreated chronic hepatitis C (CHC), relating the obtained results with iron status and disease activity markers. Two groups (CHC patients and controls) were studied. CHC patients presented significantly higher values than the control group in some parameters: ALT, AST, GGT, iron, ferritin, and transferrin saturation, and also in tert-butyl hydroperoxide initiate chemiluminescence and thiobarbituric acid-reactive substances (TBARS) as well as lower values in total radical-trapping antioxidant parameter (TRAP). TBARS showed a significant correlation with serum AST and with transferrin saturation, whereas TRAP correlated inversely with serum albumin. Serum ferritin correlated with ALT and GGT, whereas serum iron did so with GGT. In conclusion, lower antioxidant capacity, higher levels of pro-oxidants activity, and iron overload occur in untreated patients with CHC. This greater oxidative activity could play an important role in pathogenesis and evolution of hepatitis C and thus further investigations.

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Section: Discussionmentioning

confidence: 96%

Increased Oxidative Stress, Decreased Total Antioxidant Capacity, and Iron Overload in Untreated Patients with Chronic Hepatitis C

et al. 2009

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“…Hepatic iron concentration has been inversely associated with the response to antiviral therapy [11,12]. Iron removal by phlebotomy improves liver function tests [13,14] and histology [15], increases the probability of sustained HCV eradication with antiviral therapy [16–18], and decreases HCC development in CHC patients [19]. Moreover, HCV transgenic mice that are overloaded with iron are prone to develop HCC [20].…”

Section: Introductionmentioning

confidence: 99%

Reduced serum hepcidin levels in patients with chronic hepatitis C

Girelli

Pasino

Goodnough

et al. 2009

Journal of Hepatology

156

125

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Background/Aims-Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin).Methods-Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score.Results-S-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5-52.9 vs. 90.9, 76.1-108.4 ng/mL, respectively; p < 0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p < 0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p < 0.001).Conclusions-These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of

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“…The role of iron overload and the response to antiviral therapy in patients with chronic HCV infection has been debated. A few studies suggest that the removal of iron by phlebotomy may have a beneficial effect on markers of cytolysis, oxidative stress, and fibrogenesis [28][29][30]. Several studies have shown an association between iron overload and lower response rates to interferon-alpha monotherapy, which contribute to chronic HCV disease progression [9].…”

Section: Viral Hepatitismentioning

confidence: 99%

Iron chelation beyond transfusion iron overload

Pietrangelo

2007

Am. J. Hematol.

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The effects of systemic iron overload in hereditary (e.g., classic HFE hemochromatosis) or acquired disorders (e.g., transfusion-dependent iron overload) are well known. Several other iron overload diseases, with an observed mild-to-moderate increase in iron in selected organs (e.g., the liver or the brain), or with ``misdistribution{''} of iron within cells (e.g., reticuloendothelial cells) or subcellular organelles (e.g., mitochondria), have been recognized more recently. The deleterious impact of any excess iron may be high as active redox iron may directly contribute to cell damage or affect signaling pathways involved in cell necrosis-apoptosis or organ fibrosis and cancer. This article discusses the potential use of iron chelation therapy to treat iron overload from causes other than transfusion overload.

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Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection

Abstract: Although the sample number was relatively small, the results of our study suggest that phlebotomy is effective therapy for HCV patients who are nonobese, show little or no steatosis on liver histology, and have a baseline serum ALT level of less than 100 IU/l.

Cited by 28 publications

References 24 publications

Increased Oxidative Stress, Decreased Total Antioxidant Capacity, and Iron Overload in Untreated Patients with Chronic Hepatitis C

Increased Oxidative Stress, Decreased Total Antioxidant Capacity, and Iron Overload in Untreated Patients with Chronic Hepatitis C

Reduced serum hepcidin levels in patients with chronic hepatitis C

Iron chelation beyond transfusion iron overload

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