Correspondence

Hemochromatosis Presenting as Acute Liver Failure after Iron Supplementation

N Engl J Med 1998; 339:269-270July 23, 1998

Article

To the Editor:

Hemochromatosis is an autosomal recessive disorder of iron overload caused by a mutation of the HFE gene on the short arm of chromosome 6. The principal clinical features are diabetes mellitus, cirrhosis, hypogonadism, and cardiac failure,1,2 and the age at clinical presentation is usually 40 years or older.1 We report a case of acute liver failure after iron supplementation in the setting of unrecognized hemochromatosis.

A 29-year-old woman was admitted to the hospital because of a two-day history of jaundice, asthenia, hypercholuria, and hypocholia. The patient had been well until two months before admission, when she began to take an oral iron supplement (800 mg of ferrous sulfate, equivalent to 40 mg of elemental iron) for mild anemia with a low serum iron concentration. The physical examination was normal. Hematologic findings included a hematocrit of 35.6 percent, a hemoglobin concentration of 12.1 g per deciliter, a mean corpuscular volume of 103.1 μm³, and a mean corpuscular hemoglobin value of 35.1 pg. The prothrombin activity was 84 percent, the partial-thromboplastin time was 38.6 seconds (control value, 25 to 40), and the fibrinogen concentration was 237 mg per deciliter. Blood tests revealed the following results: total bilirubin, 30 mg per deciliter (conjugated bilirubin, 24.7); aspartate aminotransferase, 325 U per liter; alanine aminotransferase, 183 U per liter; γ-glutamyltransferase, 180 U per liter; alkaline phosphatase, 400 U per liter; serum ferritin, 1177 ng per deciliter (normal, 18 to 300); serum transferrin saturation, 97 percent; and serum iron, 66 μg per liter (normal, 40 to 150). Tests for hepatitis A, B, and C viruses were negative, including a test for hepatitis C virus RNA. Abdominal ultrasonography revealed no abnormalities. Wilson's disease, alpha₁-antitrypsin deficiency, porphyria, exposure to hepatotoxic drugs, drug abuse, and autoimmune hepatitis were ruled out.

A liver biopsy was performed. Histologic examination showed deposits of hemosiderin in the hepatocytes, especially in periportal areas (Figure 1Figure 1Liver-Biopsy Specimen Showing Deposits of Hemosiderin (Blue Staining) in the Hepatocytes (Perls' Stain, ×200).), and mild intracanalicular cholestasis. These findings were suggestive of hemochromatosis. The hepatic iron concentration was 268.9 μmol per gram of liver, dry weight (normal, <39), and the storage iron index was 9.27 μmol per gram of liver per year (normal, <0.8). After the patient stopped taking the iron supplement, the prothrombin activity and total bilirubin and aminotransferase concentrations gradually returned to normal. The patient is now regularly undergoing phlebotomy.

Hemochromatosis rarely presents as acute liver failure.1,2 Acute liver failure has been described in cases of neonatal hemochromatosis3 and subclinical hemochromatosis with superimposed sepsis.4 In our patient, the liver failure seems to have been caused by supplemental iron intake in the presence of unrecognized hemochromatosis. The finding of anemia with a low serum iron concentration led to the prescription of iron in a patient with iron overload. The serum ferritin concentration was not measured. The disease mechanism appears to be direct iron-induced toxicity in hepatocytes through the rapid accumulation of hemosiderin in lysosomes, leading to lipid peroxidation by iron-catalyzed free-radical reactions. As expected, soon after the iron was discontinued, the patient's liver function improved.

Francisco Pérez Roldán, M.D.
Ana Amigo Echenagusia, M.D.
Pedro González Carro, M.D.
Hospital General La Mancha-Centro, 13600 Alcázar de San Juan, Spain

4 References

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Citing Articles (4)

Citing Articles

1. 1

   MF Aslam, K Vemareddy, ZO Merhi, H Minkoff. (2010) Unusual case of postpartum hepatitis due to hereditary haemochromatosis. BJOG: An International Journal of Obstetrics & Gynaecology 117:5, 620-622
   CrossRef

2. 2

   Palle Pedersen, Nils Milman. (2009) Extrinsic factors modifying expressivity of the HFE variant C282Y, H63D, S65C phenotypes in 1,294 Danish men. Annals of Hematology 88:10, 957-965
   CrossRef

3. 3

   Faisal S Dar, Walid Faraj, Muhammad B Zaman, Adam Bartlett, Adrian Bomford, Adrian O’Sullivan, John O’Grady, Michael Heneghan, Mohamed Rela, Nigel D Heaton. (2009) Outcome of liver transplantation in hereditary hemochromatosis. Transplant International 22:7, 717-724
   CrossRef

4. 4

   &NA;. (1998) Ferrous sulfate. Reactions Weekly &amp;NA;:712, 8-9
   CrossRef