Higher age at diagnosis of hemochromatosis is the strongest predictor of the occurrence of hepatocellular carcinoma in the Swiss hemochromatosis cohort: A prospective longitudinal observational study

Abstract

Hereditary hemochromatosis (HH) is the most common genetic disease in Caucasians which is characterized by an increased intestinal iron absorption, resulting into a progressive accumulation of iron in organs including liver, heart, and pancreas, leading to their progressive dysfunction. Hepatocellular carcinoma (HCC) is a long-term complication of HH, which contributes to increased mortality.We evaluated the risk factors of HCC in a prospective cohort of Swiss hemochromatosis patients with a long-term follow-up.We included 147 patients with the mean age at diagnosis of 48 years, in whom 70% were men. Overall, 9% of the patients developed HCC during the mean follow-up time of 14 years (range 1-40 years). Patients with HCC had higher age at diagnosis (61 ± 11 vs 47 ± 13 years, P = .003), more frequently liver cirrhosis on biopsy (90% vs 37.5%, P = .004), and higher serum ferritin levels [3704 (Q1:2025, Q3:4463) vs 1338 (Q1:691, Q3:2468) μg/L, P < .001], they needed more iron removed by phlebotomy until its depletion [8.9 (Q1:7.2, Q3:10.1) vs 3.8 (Q1:1.6, Q3:8.9) g, P = .029], compared to non-HCC patients. After adjustment for possible confounders, only higher age at diagnosis remained significantly associated with HCC development (odds ratio 1.19, 95% CI 0.056-0.397, P = .001, per year).Higher age at diagnosis showed the strongest association with the occurrence of HCC in Swiss hemochromatosis patients. Patients who were diagnosed at a higher age and with a high iron overload (serum ferritin levels >1000 μg/L) require regular screening even if they have no liver cirrhosis.