The New England Journal of Medicine -- July 23, 1998 -- Volume 339, Number 4
Hemochromatosis Presenting as Acute Liver Failure after Iron Supplementation
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; (gamma)-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 1), 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 hemochromatosis (3) 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 Perez Roldan, M.D.
Ana Amigo Echenagusia, M.D.
Pedro Gonzalez Carro, M.D.
Hospital General La Mancha-Centro
13600 Alcazar de San Juan, Spain
1. Conte D, Piperno A, Mandelli C, et al. Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases. Liver 1986;6:310-5.
2. The UK Haemochromatosis Consortium. A simple genetic test identifies 90% of UK patients with haemochromatosis. Gut 1997;41:841-4.
3. Muiesan P, Rela M, Kane P, et al. Liver transplantation for neonatal haemochromatosis. Arch Dis Child Fetal Neonatal Ed 1995;73:F178-F180.
4. Simon TP, Rajakulendran S, Yeung HT. Acute hepatic failure precipitated in a patient with subclinical liver disease by vibrionic and clostridial septicemia. Pathology 1988;20:188-90.
Copyright © 1998 by the Massachusetts Medical Society. All rights reserved.