Role of HFE gene mutations in liver diseases other than hereditary hemochromatosis

Bonkovsky, Herbert L.; Obando, Jorge

doi:10.1007/s11894-999-0084-5

Cited by 23 publications

(10 citation statements)

References 52 publications

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“…In this group, 45% of patients showed levels of ferritin greater than 750 ng/ml. These results support the synergistic role or a pre‐disposing factor of the H63D genotype in these diseases, as found by different authors in NASH, PCT, and chronic hepatitis C (7, 8, 45, 46). However, Chiaverini et al (47) did not find that the H63D mutation was a PCT associated factor.…”

Section: Discussionsupporting

confidence: 89%

Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity

et al. 2006

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The frequencies of C282Y and H63D mutations of the HFE gene vary between different populations. A previous study showed an unexpectedly high H63D frequency in Chuetas (a population of Jewish descent). The present study addressed the question of the distribution of these mutations in Jewish populations from different origins and studied the possible causes of the high H63D frequency in Chuetas. Moreover, to improve the understanding of the controversial relationship between H63D homozygosity and iron overload, a group of patients with altered iron metabolism were studied. The high frequency of H63D mutation in Chuetas is not due to a high prevalence of this mutation in Sephardic Jews. Jewish populations have low C282Y and moderate H63D frequencies, suggesting slight gene flow from their surrounding populations. In accordance with historical and demographic data, genetic drift is the most probable cause for the singular H63D frequency in Chuetas. Clinically, this study of H63D homozygotes supports the conclusion that this genotype must be taken into account, because it confers an increased risk of iron overload and therefore genetic susceptibility to developing hereditary hemochromatosis or to aggravating other diseases.

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Section: Discussionsupporting

confidence: 89%

Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity

et al. 2006

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“…However, “inappropriately” low levels of hepcidin relative to the degree of hepatic or total body iron burden) are a hallmark of certain diseases, such as hereditary hemochromatosis [30, 31] and liver diseases often associated with iron overload, such as chronic hepatitis C [32-34] or alcoholic liver disease [35]. In addition, the increasingly frequent non-alcoholic fatty liver disease (NAFLD) is often associated with elevated levels of serum ferritin and sometimes with increased stainable iron in the liver [35], suggesting that levels of hepcidin may be inappropriately low.…”

Section: Resultsmentioning

confidence: 99%

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

Hwang¹,

Lee²,

Park³

et al. 2011

Clinica Chimica Acta

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BACKGROUND The measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity. METHODS In order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease. RESULTS The linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r2 = 0.9512 ± 0.0202 (n=5) for urine and r2 = 0.9709 ± 0.0291 (n=5) for serum [r2= mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2-4 h and 4-8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points. CONCLUSIONS We have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.

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“…In some settings, coexistence of more than one process may be significant in disease progression. Some examples include hepatitis C and B (8 -10), hepatitis C and alcoholic liver disease (11,12), hemochromatosis, and/or HFE mutations in patients with several other forms of viral and metabolic liver disease (13)(14)(15)(16). Although some of the histologic lesions found in various entities of differing etiologies may be similar, or may be considered "nonspecific" necroinflammatory findings, careful microscopic examination may allow for discrimination of lesions for an accurate diagnosis (7).…”

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confidence: 99%

Concurrence of Histologic Features of Steatohepatitis with Other Forms of Chronic Liver Disease

et al. 2003

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Steatohepatitis, of either alcoholic or nonalcoholic etiologies, is ultimately diagnosed by clinicalpathologic correlation and is characterized histologically by lesions that differ from the portal-based chronic inflammation and fibrosis of most other forms of chronic liver disease. With the increasing prevalence of steatohepatitis in our society, it is likely that some patients will have coexistent clinical and/or histopathologic findings of steatohepatitis concurrently with another form of liver disease. The aim of this study was to document clinical and histologic findings in biopsies in an academic referral center. Ninety-three non-allograft liver biopsies with lesions of both steatohepatitis and another liver disease were retrospectively identified in 85 patients. The finding of coexisting disease represented 5.5% of all hepatitis C biopsies and 4.0% of other forms of chronic liver disease in the 34 month time period. Clinical chart review of patients with concurrent disease showed the following: Group 1, patients with hepatitis C (n ‫؍‬ 54); Group 2, patients with hepatitis C and prior or current history of more than 80 g/d alcohol consumption (n ‫؍‬ 20); Group 3, patients with other forms of chronic liver disease (n ‫؍‬ 11). Groups 1 and 3 had <10 g/d alcohol use. Obesity (body mass index >30) was noted in 75%, 60%, and 33% respectively, while 94%, 87% and 100% of patients were considered overweight (body mass index > 25). Diabetes was reported in 35%, 25%, and 9%. The concurrence of clinical and histologic features of steatohepatitis with another chronic liver disease may be a reflection of the frequency of steatohepatitis in the population at large.

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Role of HFE gene mutations in liver diseases other than hereditary hemochromatosis

Cited by 23 publications

References 52 publications

Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity

Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications of H63D homozygosity

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

Concurrence of Histologic Features of Steatohepatitis with Other Forms of Chronic Liver Disease

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