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  • Title: Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis?
    Author: Adams PC.
    Journal: Am J Gastroenterol; 2001 Feb; 96(2):567-9. PubMed ID: 11232708.
    Abstract:
    OBJECTIVE: The relationship between the degree of iron overload and the presence of cirrhosis has not been clearly established in hemochromatosis. Severe iron overload occurs without cirrhosis and moderate iron overload can occur with cirrhosis. Previous estimates may have overestimated the problem because of the overdiagnosis of hemochromatosis in patients with alcoholic liver disease and chronic viral hepatitis. The objective of this study was to determine if a threshold for hepatic iron concentration leads to the development of cirrhosis in C282Y hemochromatosis. METHODS: This study included only hemochromatosis patients who were homozygotes for the C282Y mutation of the HFE gene and had undergone liver biopsy with hepatic iron concentration. Analysis of the thresholds for cirrhosis were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Data were available on 100 C282Y homozygotes (62 men, 38 women; mean age 51, range 18-74 yr). ROC curve analysis showed an area under the curve for hepatic iron concentration versus cirrhosis of 0.85 (95% CI = 0.75-0.96). The threshold for the prediction of cirrhosis was 283 micromol/g. At that threshold, the sensitivity was 85% and specificity 84%. CONCLUSIONS: From this analysis, it appears that a hepatic iron concentration >283 micromol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.
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