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Serum Ferritin Level Predicts Advanced Hepatic Fibrosis among U.S. Patients with Phenotypic Hemochromatosis

Elizabeth D. Morrison, MD; David J. Brandhagen, MD; Pradyumna D. Phatak, MD; James C. Barton, MD; Edward L. Krawitt, MD; Hashem B. El-Serag, MD, MPH; Stuart C. Gordon, MD; Mark V. Galan, MD; Bruce Y. Tung, MD; George N. Ioannou, MD, MS; and Kris V. Kowdley, MD
[+] Article and Author Information

From University of Washington, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; Rochester General Hospital and University of Rochester, Rochester, New York; Southern Iron Disorders Center, Birmingham, Alabama; University of Vermont, Burlington, Vermont; Houston Veterans Administration Medical Center, Baylor College of Medicine, Houston, Texas; Health Services Research and Development Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and William Beaumont Hospital, Royal Oak, Michigan.


*The odds ratio form of Bayes' theorem states that the post-test odds = pretest odds × likelihood ratio. The likelihood ratio is the frequency of a finding in patients with a disease divided by its frequency in patients who don't have the disease.

Grant Support: In part by grants DK02957 and DK 38215 from the National Institutes of Health. Dr. Ioannou is a Fellow at the Health Services Research and Development program of the Veterans Affairs Puget Sound Health Care system.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Kris V. Kowdley, MD, Division of Gastroenterology/Hepatology, University of Washington, 1959 NE Pacific Street, Box 356174, Seattle, WA 98195; e-mail, kkowdley@u.washington.edu.

Current Author Addresses: Drs. Morrison, Tung, Ioannou, and Kowdley: Division of Gastroenterology/Hepatology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195.

Dr. Brandhagen: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

Dr. Phatak: Department of Medicine, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621.

Dr. Barton: G-105, 2022 Brookwood Medical Center Drive, Birmingham, AL 35209.

Dr. Krawitt: Department of Medicine, University of Vermont College of Medicine, Given Building, Burlington, VT 05405.

Dr. El-Serag: Houston Veterans Administration Medical Center (152), 2002 Holcombe Boulevard, Houston, TX 77030.

Drs. Gordon and Galan: William Beaumont Hospital, Division of Gastroenterology and Hepatology, 3601 West 13 Mile Road Royal Oak, MI 48073.

Author Contributions: Conception and design: E.D. Morrison, D.J. Brandhagen, P.D. Phatak, E.L. Krawitt, K.V. Kowdley.

Analysis and interpretation of the data: E.D. Morrison, D.J. Brandhagen, H.B. El-Serag, B.Y. Tung, G.N. Ioannou, K.V. Kowdley.

Drafting of the article: E.D. Morrison, E.L. Krawitt, H.B. El-Serag, K.V. Kowdley.

Critical revision of the article for important intellectual content: E.D. Morrison, D.J. Brandhagen, P.D. Phatak, J.C. Barton, H.B. El-Serag, S.C. Gordon, M.V. Galan, G.N. Ioannou, K.V. Kowdley.

Final approval of the article: D.J. Brandhagen, J.C. Barton, H.B. El-Serag, S.C. Gordon, B.Y. Tung, K.V. Kowdley.

Provision of study materials or patients: E.D. Morrison, D.J. Brandhagen, P.D. Phatak, J.C. Barton, E.L. Krawitt, S.C. Gordon, B.Y. Tung, K.V. Kowdley.

Statistical expertise: J.C. Barton, H.B. El-Serag, G.N. Ioannou.

Obtaining of funding: K.V. Kowdley.

Administrative, technical, or logistic support: K.V. Kowdley.

Collection and assembly of data: E.D. Morrison, D.J. Brandhagen, P.D. Phatak, M.V. Galan, K.V. Kowdley.


Ann Intern Med. 2003;138(8):627-633. doi:10.7326/0003-4819-138-8-200304150-00008
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Of 284 patients referred to the study, 45 patients were excluded because of lack of liver biopsy; an additional 57 (20%) patients were excluded because of the following reasons: incomplete phenotypic expression (that is, patients did not meet any of three phenotypic criteria [hepatic iron concentration < 4000 µg/g dry weight, hepatic iron index < 1.9, or < 4 g of iron removed by quantitative phlebotomy]) (n = 24), another obvious cause of liver disease (nonalcoholic steatohepatitis, hepatitis C, or other) (n = 14), or average alcohol intake greater than 20 g/d (n = 19). Of 239 eligible patients, 182 (65%) met all inclusion and exclusion criteria (Figure 1).

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Figure 1.
The use of serum ferritin in predicting presence or absence of advanced hepatic fibrosis among 182 patients with the hemochromatosis phenotype.

Overall numbers of patients evaluated for participation, patients excluded from participation (and reasons for exclusion), as well as patients with elevated serum ferritin levels and patients with and without advanced fibrosis are shown.

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Figure 2.
The receiver-operating characteristic curve of serum ferritin levels as a diagnostic test for advanced hepatic fibrosis among patients with hemochromatosis.

Point A indicates the calculated values for a serum ferritin level cutoff value of 1500 µg/L, point B for 1000 µg/L, and point C for 500 µg/L.

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Summary for Patients

Low Serum Ferritin Level Rules Out Advanced Liver Disease in Hemochromatosis

The summary below is from the full report titled “Serum Ferritin Level Predicts Advanced Hepatic Fibrosis among U.S. Patients with Phenotypic Hemochromatosis.” It is in the 15 April 2003 issue of Annals of Internal Medicine (volume 138, pages 627-633). The authors are E.D. Morrison, D.J. Brandhagen, P.D. Phatak, J.C. Barton, E.L. Krawitt, H.B. El-Serag, S.C. Gordon, M.V. Galan, B.Y. Tung, G.N. Ioannou, and K.V. Kowdley.

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