Brian Schmitt, MD, MPH; Robert M. Golub, MD; Richard Green, MD
Grant Support: The paper was written under contract with the American College of Physicians.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Brian Schmitt, MD, MPH, Medicine and Neurology Service Line (111), Hines Veterans Affairs Hospital, Hines, IL 60141; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Schmitt: Medicine and Neurology Service Line (111), Hines Veterans Affairs Hospital, 5th Avenue and Roosevelt, Hines, IL 60141.
Dr. Golub: Northwestern University, 676 North St. Clair, Suite 200, Chicago, IL 60611.
Dr. Green: Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611.
Therapeutic phlebotomy for hereditary hemochromatosis is relatively safe and presumably efficacious when offered before cirrhosis develops, so screening primary care patients is of substantial interest.
To conduct a systematic review of the evidence on 1) the prevalence of the disease in primary care, 2) the risk for morbid or fatal complications for untreated patients, 3) the diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease, 4) the efficacy of early treatment, and 5) whether the benefits of screening outweigh the risks.
MEDLINE search from 1966 through April 2004, complemented by reference review of identified original studies and review articles published in English.
PubMed Clinical Queries filters search of prognosis, diagnosis, etiology, or treatment were used depending on the question. Two authors reviewed all titles and abstracts.
Two investigators independently reviewed extracted data.
The prevalence of hereditary hemochromatosis was 1 in 169 patients to 1 in 556 patients (n = 3 studies). Uncontrolled, prospective studies of genetic homozygous patients did not consistently identify a link to overt hereditary hemochromatosis. A serum ferritin level less than 1000 µg/L was predictive of absence of cirrhosis. Six studies demonstrated reduced survival in patients with cirrhosis. Diagnostic studies varied with respect to case definition. No blinded, independent comparisons of screening tests with the gold standard (biopsy or results of quantitative phlebotomy) or randomized, controlled trials of phlebotomy were identified. Cost-effectiveness analysis was limited by lack of prospective data on the natural history of the disease.
Varied case definition and lack of prospective cohort studies or randomized trials.
The available evidence does not demonstrate that benefits outweigh the risks and costs of screening for hemochromatosis.
Table 1. Prevalence of Hereditary Hemochromatosis in Primary Care Settings
Table 2. Prevalence of Hereditary Hemochromatosis in Various General Population Settings
The selection and exclusion of articles to address subquestion 1 about the prevalence of hereditary hemochromatosis.
The selection and exclusion of articles to address subquestion 2 about the magnitude of complications with primary iron overload (biochemical measures).
Table 3. Longitudinal Studies of Primary Iron Overload and Overt Hemochromatosis or Complications
Table 4. Relationship between Primary Iron Overload Defined by Transferrin Saturation and Serum Ferritin Level and Diabetes Mellitus
Table 5. Relationship between Primary Iron Overload Defined by Transferrin Saturation or Serum Ferritin Level and Cirrhosis
Table 6. Relationship between Primary Iron Overload Defined by Transferrin Saturation or Serum Ferritin Level and Cardiomyopathy or Mortality
The selection and exclusion of articles to address subquestion 2 about the magnitude of complications with primary iron overloading (iron deposition).
Table 7. Relationship between Primary Iron Overload Defined by Tissue Iron Deposition and Complications
The selection and exclusion of articles to address subquestion 3 about the diagnostic usefulness of transferrin saturation and serum ferritin level.
The selection and exclusion of articles to address subquestion 4 about the treatment of hereditary hemochromatosis.
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May 18, 2006
Targeted testing for hemochromatosis
The review and guidelines for hemochromatosis screening published in the Annals identified several gaps in our knowledge of the disease. However, one particular scenario was not addressed: the patient with incidentally noted hepatic dysfunction and abnormal iron indices. This type of patient is often encountered in the course of routine clinical practice, but has not been the focus of any study. Would these supposed high-risk patients warrant genetic testing, as suggested in the previous AASLD guidelines from 2001?
Schmitt B, Golub RM, Green R. Screening Primary Care Patients for Hereditary Hemochromatosis with Transferrin Saturation and Serum Ferritin Level: Systematic Review for the American College of Physicians. Ann Intern Med. 2005;143:522–536. doi: https://doi.org/10.7326/0003-4819-143-7-200510040-00011
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Published: Ann Intern Med. 2005;143(7):522-536.
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