Screening for Hereditary Hemochromatosis in Siblings and Children of Affected Patients: A Cost-Effectiveness Analysis

15 February 2000 | Volume 132 Issue 4 | Pages 261-269

Background: Screening for hereditary hemochromatosis is traditionally done by using serum iron studies. However, mutation analysis of the hemochromatosis-associated HFE gene has recently become available.

Objective: To compare the cost-effectiveness of no screening with four screening strategies that incorporate HFE gene testing or serum iron studies.

Design: Cost-effectiveness analysis.

Data Sources: Published literature.

Target Population: Siblings and children of an affected proband.

Time Horizon: Lifetime from 10 years of age (children) or 45 years of age (siblings).

Perspective: Societal.

Intervention: 1] Serum iron studies. 2) Gene testing of the proband. If the proband is homozygous (C282Y+/+), the spouse undergoes gene testing; if he or she is heterozygous [C282Y+/–], the children undergo gene testing. 3) Gene testing of the proband; if he or she is homozygous, relatives undergo gene testing. 4) Direct gene testing of relatives.

Outcome Measures: Cost per life-year saved and incremental cost-effectiveness ratio.

Results of Base-Case Analysis: In children, HFE gene testing of the proband was the most cost-effective strategy for screening one child (incremental cost-effectiveness ratio, $508 per life-year saved). HFE gene testing of the proband followed by testing of the spouse was the most cost-effective strategy for screening two or more children (incremental cost-effectiveness ratio, $3665 per life-year saved). In siblings, all screening strategies were dominant compared with no screening. Strategies using HFE gene testing were less costly than serum iron studies.

Results of Sensitivity Analysis: Despite varying the prevalence of mutations and regardless of the cost of the genetic test in one- and two-way sensitivity analyses, HFE gene testing remained cost-effective.

Conclusions: HFE gene testing for the C282Y mutation is a cost-effective method of screening relatives of patients with hereditary hemochromatosis.

Author and Article Information

From Houston Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Ann Arbor Veterans Affairs Medical Center and University of Michigan Medical Center, Ann Arbor, Michigan; and University of Washington, Seattle, Washington.

Acknowledgment: The authors thank Professor Denis M. McCarthy for his overall support and Amnon Sonnenberg, MD, MSc, for advice on mathematical issues.

Grant Support: In part by a Glaxo Wellcome Foundation for Digestive Health Award for Outcomes Research (Dr. El-Serag) and by the Veterans Affairs HSR&D Houston Center of Excellence.

Requests for Single Reprints: John M. Inadomi, MD, Divisions of Gastroenterology and Health Services Research, Ann Arbor Veterans Affairs Medical Center, 2215 Fuller Road (111-D), Ann Arbor, MI 48105; e-mail, jinadomi{at}umich.edu.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

Current Author Addresses: Dr. El-Serag: Health Services Research Section (152), Houston Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX 77030.

Dr. Inadomi: Divisions of Gastroenterology and Health Services Research, Ann Arbor Veterans Affairs Medical Center, 2215 Fuller Road (111-D), Ann Arbor, MI 48105; e-mail, jinadomi{at}umich.edu.

Dr. Kowdley: Division of Gastroenterology/Hepatology, University of Washington Medical Center, Box 356154, Seattle, WA 98195.

Author Contributions: Conception and design: H.B. El-Serag, J.M. Inadomi, K.V. Kowdley.

Analysis and interpretation of the data: H.B. El-Serag, J.M. Inadomi, K.V. Kowdley.

Drafting of the article: H.B. El-Serag, J.M. Inadomi, K.V. Kowdley.

Critical revision of the article for important intellectual content: H.B. El-Serag, J.M. Inadomi, K.V. Kowdley.

Final approval of the article: H.B. El-Serag, J.M. Inadomi, K.V. Kowdley.

Statistical expertise: H.B. El-Serag, J.M. Inadomi.

Administrative, technical, or logistic support: H.B. El-Serag.