Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 11;4(4):381-390.
doi: 10.3138/canlivj-2021-0016. eCollection 2021 Fall.

Survival and development of health conditions after iron depletion therapy in C282Y-linked hemochromatosis patients

Paul C Adams  1 , Lucie Richard  2 , Matthew Weir  1   2 , Mark Speechley  3
Affiliations

Survival and development of health conditions after iron depletion therapy in C282Y-linked hemochromatosis patients

Paul C Adams et al. Can Liver J. .

Abstract

Background: We report long-term survival and development of selected health conditions in Ontario-based referred and screened C282Y homozygotes for hemochromatosis treated by phlebotomy compared with an untreated control group known to be without HFE mutations.

Methods: Patient characteristics and outcomes (all-cause mortality, liver cancer, diabetes, cirrhosis, hip or knee joint replacement, and osteoarthritis) were ascertained using a linked health administrative database held at ICES. Outcomes were assessed between groups without the outcome at baseline using Cox proportional hazards regression adjusted for age and sex. All C282Y homozygotes with elevated serum ferritin were treated by phlebotomy to reach serum ferritin of 50 µg/L. Our cohort included 527 C282Y homozygotes (311 men, 216 women, mean age 48 years) and 12,879 control participants (5,667 men and 7,212 women).

Results: C282Y homozygotes had an increased risk of all-cause mortality (aHR 1.44 [1.19-1.75], p <0.001); hepatocellular carcinoma (aHR 8.30 [3.97-17.34], p <0.001); hip or knee joint replacement (aHR 3.06 [2.46-3.81], p <0.001); osteoarthritis (aHR 1.72 [1.47-2.01], p <0.001); and cirrhosis (aHR 3.87 [3.05-4.92], p <0.001). C282Y homozygotes did not have an increased risk for diagnosis of diabetes) (aHR 0.84 [0.67-1.07], p = 0.16) during follow-up (median 17.7 y).

Conclusions: C282Y homozygotes experience higher death and complication rates than individuals without HFE mutations, despite treatment by phlebotomy. Diabetes did not increase after phlebotomy therapy.

Keywords: hemochromatosis; iron; iron overload; phlebotomy.

PubMed Disclaimer

Conflict of interest statement

The authors have nothing to disclose.

Figures

Figure 1:
Figure 1:
Cohort creation HEIRS = Hemochromatosis and iron overload study
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005;352(17):1769–78. 10.1056/NEJMoa041534. Medline: - DOI - PubMed
    1. McDonell S, Preston B, Jewell S, et al. A survey of phlebotomy among persons with hemochromatosis. Transfusion. 1999;39(6):651–6. 10.1046/j.1537-2995.1999.39060651.x. Medline: - DOI - PubMed
    1. Adams PC, Deugnier Y, Moirand R, Brissot P. The relationship between iron overload, clinical symptoms and age in 410 hemochromatosis patients. Hepatology. 1997; 25(1):162–6. 10.1002/hep.510250130. Medline: - DOI - PubMed
    1. Lim DR, Vidyasankar G, Phua C, Borgaonkar M. Clinical penetrance of hereditary hemochromatosis-related endo-organ damage of C282Y homozygosity, a Newfoundland experience. Clin Transl Gastroenterol. 2020; 11(11):e00258. 10.14309/ctg.0000000000000258. Medline: - DOI - PMC - PubMed
    1. Benchimol E, Smeeth L, Guttmann A, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Med. 2015;12(10):e1001885. 10.1371/journal.pmed.1001885. Medline: - DOI - PMC - PubMed

LinkOut - more resources