Hemochromatosis in Italy in the Last 30 Years: Role of Genetic and Acquired Factors

Abstract

The clinical presentation of hereditary hemochromatosis has changed markedly in recent years. The aim of this study was to analyze a large series of consecutive Italian patients with hemochromatosis diagnosed between 1976 and 2007 to determine whether the genetic background and the presence of acquired risk factors influenced the severity of iron overload and the natural history of the disease. A cohort of 452 Italian patients with iron overload-338 HFE-related (C282Y homozygotes or compound C82Y/H63D heterozygotes) and 114 non-HFE-related-were followed prospectively for a median of 112 months. Alcohol intake, smoking habits, and iron removed to depletion were similar in patients with and without HFE-related iron overload. Hepatitis B virus (4% and 9%; P ‫؍‬ 0.04) and hepatitis C virus (6% and 19%; P ‫؍‬ 0.002) infections were more frequent in patients with non-HFErelated iron overload. Seventy-three percent of patients with HFE and 61% of patients with non-HFE-related disease had no acquired risk factor. Cirrhosis was significantly more frequent in non-HFE patients independent of the presence of acquired risk factors (P ‫؍‬ 0.02). Sex, alcohol intake, prevalence of smoking, hepatitis C virus infection, glucose, lipids, iron-related parameters, and prevalence of C282Y/H63D differed significantly over the years. At enrollment, cirrhosis was present in 145 cases and was significantly more frequent in the first decade (80%, 47%, and 13%; P ‫؍‬ 0.001). Survival did not differ across the decades in cirrhotic patients; hepatocellular carcinoma occurred similarly in HFE and non-HFE patients.

Hepatic iron overload and hepatocellular carcinoma

“…A relative risk of tumor formation in the iron-loaded liver of between 20 and 200 has been calculated [11][12][13][14]. The incidence of HCC in patients with HH is approximately 8-10% in most surveys, but figures as low as 1.7% have been recorded [14][15][16][17][18][19][20]. Long-term survival in patients with HH and cirrhosis is significantly shorter than that in matched controls, a phenomenon attributed mainly to the development of HCC.…”

“…Long-term survival in patients with HH and cirrhosis is significantly shorter than that in matched controls, a phenomenon attributed mainly to the development of HCC. Cirrhosis is present in almost all patients who develop HCC, but whether or not the risks of developing HCC are greater in patients with cirrhosis complicating HH than in those with other causes of cirrhosis remains uncertain [14,20]. Also uncertain is whether patients with HH are at increased risk of developing cancers in organs other than the liver [14,20].…”

Recent advances in hemochromatosis: a 2015 update

“…Types I-III are linked to altered or reduced expression of hepcidin [11,25,27], whereas type IV results from reduced iron export [1,28]. Mutations in HFE, HJV, HAMP, TFR2 and SLC40A1 have been linked to the various types of hemochromatosis [11,25,29], each displaying different onsets, severities and prevalences [2,4,9,25,27,[29][30][31][32][33] (Table 1).…”

“…This implicates other genetic and non-genetic factors in the disease [31]. To this end an Italian study Non-heme iron is taken up through the divalent metal transporter (DMT1) protein as Fe 2?…”

Cryptogenic Chronic Hepatitis and Its Changing Guise in Adults

“…The task of exclusion is complicated by the varying phenotype of hereditary hemochromatosis and the common occurrence of abnormal iron studies and HFE (high iron FE) mutations in patients with other chronic liver diseases [139][140][141] (Table 1). Hereditary hemochromatosis has had a changing clinical phenotype as the pathogenic roles and the genetic determinants of the diverse proteins associated with the disease have been clarified [26,142].…”