Value of Hepatic Iron Measurements in Early Hemochromatosis and Determination of the Critical Iron Level Associated With Fibrosis

Abstract

The role of the measurement of hepatic iron in the diagnosis of genetic hemochromatosis was studied, with particular reference to the differentiation of early hemochromatosis from alcoholic siderosis and the critical hepatic iron concentration associated with fibrosis in hemochromatosis. Hepatic iron was measured in 30 homozygous relatives of 17 hemochromatosis probands, 8 heterozygous relatives, 51 patients with alcoholic liver disease and 40 control subjects. Hepatic iron concentrations were greatly increased in the majority of homozygous hemochromatosis subjects, and there was little overlap with the other groups. In the absence of alcoholism, fibrosis or cirrhosis in hemochromatosis was present only with hepatic iron concentrations above a threshold of approximately 400 mumoles per gm (22.3 mg per gm) dry weight. In some heterozygous hemochromatosis subjects and in some alcoholic patients, hepatic iron concentrations were in the range seen in young homozygous subjects. However, an age-related rise in hepatic iron was seen only in hemochromatosis homozygotes, and calculation of an hepatic iron index (hepatic iron/age) resulted in a clear distinction between homozygotes and the other three groups. It is concluded: that chemical measurement of hepatic iron concentration, when corrected for the age of the subject, reliably distinguishes early hemochromatosis from alcoholic siderosis, and, that there appears to be a threshold level of hepatic iron above which there is a high risk of fibrosis.

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

“…These results suggest that hepatic iron loading below the hemochromatosis range (less than 2 times the upper limit of normal, normal range 3‐33 mmol/kg29) may actually be beneficial in terms of insulin sensitivity. In contrast, the association between excess hepatic iron seen in hemochromatosis and insulin resistance and diabetes is well established 6.…”

Iron overload syndromes and the liver

“…38 Its value has diminished in the era of genetic testing but iron quantitation can still play a diagnostic and prognostic role in some instances. Tissue iron analysis must be performed in a highly qualified laboratory where rigorous control of processing and analytical procedures are followed to assure accurate results.…”

“…In uncomplicated HH, most patients with iron concentrations of 22 000 mg Fe/g dry weight liver likely will have developed fibrosis as well. 38 The concept of the hepatic iron index (HII) was introduced by Bassett et al 38 in 1986, and it has proven useful, especially in the interpretation of mild to moderate degrees of hepatic iron overload. The HII was developed to account for the progressive iron accumulation that occurs over time in HH-a given amount of iron at age 25 indicates a more rapid accumulation of iron than the same amount of iron in a 50-year-old individual ( Figure 7).…”

the screening, diagnosis and optimal management of haemochromatosis

“…Increasing age 47 and serum ferritin levels 20 are also associated with cirrhosis but no reliable threshold level for either of these factors has yet been found. A threshold level of hepatic iron concentration above which cirrhosis occurs has been found in some studies, 45,49 but not others, 20,47 but of course liver biopsy is still required to determine this. Liver biopsy should therefore continue to be used in the management of haemochromatosis until a reliable serum marker or other non-invasive test for cirrhosis is identi®ed.…”

“…44 At present, liver biopsy with a histological assessment of the degree and distribution of iron stores, together with a biochemical quanti®cation of the hepatic iron stores, is the gold standard in diagnosing an index case of haemochromatosis. 45,46 The subsequent diagnosis of iron overload in an HLA-identical sibling clinches the diagnosis. Liver biopsy is also the only reliable way to determine the presence or absence of cirrhosis, the most important prognostic factor in haemochromatosis.…”