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CDDW Abstracts
LONG TERM SURVIVAL ANALYSIS IN C282Y HOMOZYGOTES FOR THE HEMOCHROMATOSIS GENE (HFE)
J Wojcik, M Speechley, S Chakrabarti, A Kertesz, PC Adams Departments of Medicine, Pathology and Epidemiology and Biostatistics, University of
Western Ontario, London, Ontario, Canada
093
Background/Aims: Previous studies on the long term survival of hemochromatosis have included iron loaded patients with other diseases (alcoholic siderosis, viral hepatitis) and excluded hemochromatosis patients without significant iron overload. Genetic testing for the C282Y mutation of the HFE gene has allowed for a genotypic definition of disease independent of the degree of iron overload.
Methods: All available patients that have been diagnosed with hemochromatosis at this hospital were recontacted for genetic testing and to determine health status. All iron loaded patients have had venesection therapy to maintain the serum ferritin in the low normal range. The factors affecting long term survival in hemochromatosis patients were studied using Kaplan-Meier survival analysis. Genetic test result was inferred in 12 deceased cases based on HLA identity to a tested sibling.
Results: Genetic testing was available on 226 cases and 96% were C282Y homozygotes (217 homozygotes, 143 men, 74 women, median age 51). There were 121 probands cases, 80 family members and 16 cases found through population screening. Mean follow up period was 7.7 years (range 0.1 – 39 years). Mean serum ferritin was 1,216±1,331 µg/L and transferrin saturation (TS) was 73±20%. There were 23 homozygotes with a TS < 45% and 29 homozygotes with a ferritin < 200 µg/L. Cirrhosis was present in 18%, diabetes in 18%, arthritis in 36%, and heart disease in 12%. There were 25 deaths over the follow up period (7 HCC). Actuarial survival at 10 years was 93% and at 20 years was 67%. Cirrhotic patients had a significantly decreased survival compared to non-cirrhotic patients (p = 0.002, log-rank test).
Conclusions: C282Y homozygotes have an excellent long term survival. The presence of cirrhosis is the major clinical factor affecting long term survival. Genetic testing has a high sensitivity as a diagnostic test for hemochromatosis but many homozygotes (10 – 15%) will not have significant iron overload. Patients with unexplained abnormalities in TS or ferritin should have C282Y genetic testing and venesection therapy to prevent organ damage and improve long term survival.