SESSION I: UPDATE OF CLINICAL AND
duration of iron overload and, if cirrhosis is present, is not
PATHOLOGICAL FEATURES OF HHC
prevented by depletion of hepatic iron stores by venesection therapy. Over the last decade, the typical clinical presentation of C. Niederau 1 found a marked difference in presentation, hereditary homozygous HLA (human leukocyte antigen)survival, and causes of death among patients from Du ¨sseldorf linked hemochromatosis (HHC) has changed from a sympcomparing data from two different periods. While HCC was tomatic constellation, often including arthropathy, weakness, the most common cause of death, cirrhosis, cardiomyopathy, lethargy, and cardiac symptoms, to an asymptomatic patient and diabetes were more frequent causes of death than might found on routine screening to have abnormal liver chemisbe expected in a general population. Early diagnosis and tries, an increased transferrin saturation, or hyperglycemia. treatment prevent the complications of HHC and result in a significant improvement in life expectancy.
A. Piperno 3 presented data for prognostic factors in the development of HCC as a complication of HHC. Twenty-eight Abbreviations: HHC, hereditary homozygous (HLA-linked) hemochromatosis; HLA, human leukocyte antigen; HCC, hepatocellular carcinoma; HII, hepatic iron index; Fe, ferrous; of 97 patients with cirrhosis developed HHC, compared with TGFb1, transforming growth factorb1; mRNA, messenger RNA; HIC, hepatic iron concentranone of the 55 patients without cirrhosis at the time of diagtion; IFN, interferon; NF-E2, erythroid nuclear transcription factor 2; Tf, transferrin; NTBI, nosis. A multivariate analysis showed that age (ú55 years), nontransferrin bound iron; SA, sideroblastic anemia; ALA, 5-aminolevulinate; DFO, deferthe presence of hepatitis B surface antigen, and alcohol abuse oxamine; RE, reticulo-endothelial; IRP, iron regulatory protein; TfR, transferrin receptor; IRE, iron responsive element; cM, centimorgan; YAC, yeast artificial chromosome. were the only factors predictive of HCC development. Pa-From The Departments of 1 Medicine, 2 Biochemistry and Molecular Biology, and 3 The tients with all three factors had a 150-fold increase in relative Center for Study of Disorders of Iron and Porphyrin Metabolism, University of Massachurisk for liver cancer, compared with a matched normal popusetts School of Medicine, Worcester, MA; the Department of 4 Physiology and 5 Medicine,