Management of patients with hereditary hemochromatosis
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Bruce R Bacon, MD
Bruce R Bacon, MD
- Professor of Internal Medicine
- Saint Louis University School of Medicine
Hereditary hemochromatosis (HH, genetic hemochromatosis) is an inherited disorder in which mutations in the HFE gene or, less commonly, hemojuvelin, hepcidin, ferroportin, or ceruloplasmin genes (table 1), result in increased intestinal iron absorption, iron overload, and, in advanced disease, tissue damage. The treatment of HH will be discussed here. The genetics, pathophysiology, clinical manifestations, diagnosis, and issues related to screening for HH are discussed separately. (See "Genetics of hereditary hemochromatosis" and "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Approach to the patient with suspected iron overload" and "Screening for hereditary hemochromatosis".)
RATIONALE FOR TREATMENT
Symptomatic patients — Although there have been no randomized, controlled studies of phlebotomy versus observation in patients with HH, the following observations provide strong support for the early treatment of symptomatic HH using this modality.
Effect on survival — The major causes of death in symptomatic HH are decompensated cirrhosis, hepatocellular carcinoma (HCC), diabetes mellitus, and cardiomyopathy [1-3], with HCC being responsible for approximately 45 percent of deaths in the patients with HH who develop HCC . A number of observational studies have indicated that these complications can be minimized, or even avoided, when adequate treatment (ie, phlebotomy) is initiated when this disorder is promptly diagnosed and treated. As an example, with few exceptions, those with HH and HCC do so in the presence of cirrhosis, consistent with observations that treatment of HH prior to the development of cirrhosis has a major impact on overall survival in this disorder. (See 'Prognosis' below.)
●An early study, reported in 1976, in 85 patients with HH treated with phlebotomy as compared with a historical group of 26 untreated patients, indicated significantly longer five-year (66 versus 18 percent) and 10-year (32 versus 6 percent) overall survivals for the treated group . Of interest, 10 of the 85 treated patients, all of whom had cirrhosis at the time of diagnosis, died of HCC 3 to 15 years later, despite having received treatment with phlebotomy.
●In an observational study of 163 patients with HH, survival was similar to that of a normal population in the 51 patients in whom treatment (eg, phlebotomy) was initiated before the development of cirrhosis or diabetes [1,2]. Further, overall survival was markedly reduced in those patients who could not be depleted of iron during the first 18 months of phlebotomy therapy, as compared with those who could be depleted during this time interval.
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- RATIONALE FOR TREATMENT
- Symptomatic patients
- - Effect on survival
- - Effect on disease complications
- Asymptomatic patients
- - Family screening
- - Population screening
- MANAGEMENT OF HH
- Patients without iron overload
- Patients with iron overload
- - Schedule
- - Endpoints
- - Maintenance
- Iron chelation
- Dietary limitations
- - Dietary iron intake
- - Agents for reducing iron absorption
- - Avoidance of excessive ethanol
- - Avoidance of ascorbic acid (vitamin C) supplements
- - Avoidance of uncooked seafood
- Screening for hepatocellular carcinoma
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS