Clinical Manifestation of Hereditary Hemochromatosis and Prevalence of Hepatocellular Carcinoma in the Swiss Hemochromatosis Cohort

Hereditary hemochromatosis (HH) is the most common identified genetic disease in Europe, occurring with a prevalence of roughly one in 200 individuals (1-4). Through the advances in diagnosis and the deeper insight into the genetic background, the clinical manifestation of HH has shifted to a milder picture over the last decades (5-8). However, HH still carries an increased risk of hepatocellular carcinoma (HCC) (9-12). Our study aims to provide current data on the clinical manifestation of HH among patients with clinically documented iron overload. By presenting a more accurate picture of HH, we support the early diagnosis of the disease to prevent life-threatening complications. We analyzed the prevalence of HCC in our cohort. Additionally, we tried to identify risk factors for HCC with the goal of effective screening measures in mind. From an established database of HH patients, patient charts were analyzed for the clinical presentation at the time of diagnosis of HH. Information on current health status and liver imaging was gathered to determine the prevalence of HCC. Univariate comparison and multiple logistic regression were used to asses risk factors associated with the development of HCC. In our cohort, 29% of all patients presented without signs or symptoms of secondary organ damage at the time of diagnosis of HH. The most frequent clinical abnormalities were arthropathy of the metacarpophalangeal joints (MCP joints) and elevated liver enzymes. The overall prevalence of HCC in our cohort was 9%. Factors associated with the development of HCC among patients with high iron overload (serum ferritin >1000μg/l) on univariate analysis were age at diagnosis of HH, body mass index, serum ferritin levels and liver fibrosis. On multiple logistic regression, only age at diagnosis of HH showed a significant association with HCC. In conclusion, three main findings result from our study: (1) Arthropathy of the MCP joints and elevated liver enzymes are the most frequent and relatively early signs of HH. Their presence should prompt further investigation. (2) HCC is still an important complication of HH. (3) Besides liver cirrhosis and the degree of iron overload, two well established risk factors for the development of HCC (10,13), age at diagnosis of HH seems to be an important risk factor, especially among patients with high iron overload