Liver Iron, HFE Gene Mutations, and Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis

Background & Aims: The influence of HFE gene mutations and liver iron overload on hepatocellular carcinoma (HCC) occurrence in patients with cirrhosis is subjected to controversial results. The aim of this work was to clarify this influence in a large cohort of prospectively followed-up cirrhotic patients classified according to the cause of their liver disease. Methods: Three hundred one consecutive cirrhotic patients (162 alcoholics and 139 HCV-infected patients) were included at time of diagnosis of cirrhosis and followed-up. Liver iron overload on initial biopsy according to modified Deugnier’s score and C282Y/H63D HFE gene mutations were assessed. Results: In patients with alcoholic cirrhosis (mean iron score, 2.0 ± 3.0; mean time of follow-up, 66.1 ± 45.1 months), 40 (24.6%) developed HCC. Thirteen (8.02%) were heterozygotes for C282Y HFE gene mutation and had higher hepatic iron scores (3.6 ± 3.8 vs 1.9 ± 2.8, respectively, P = .05). In univariate analysis, liver iron overload as a continuous variable (HR, 1.23 [1.13–1.34], P < .001) or in binary coding with an optimal threshold of iron score ≥2.0 (HR, 4.1 [2.1–7.3], P < .0001) and C282Y mutation carriage (HR, 2.7 [1.2–6.3], P = .01) were risk factors for HCC. In multivariate analysis, liver iron and C282Y mutation carriage remained independent risk factors for HCC. In patients with HCV-related cirrhosis (C282Y mutation carriage, 17 [12.23%]; mean liver iron score, 0.9 ± 1.9; mean time of follow-up, 85.5 ± 42.1 months; HCC, 63 [45.32%] patients), C282Y mutation carriage and liver iron were not associated with HCC occurrence. Conclusions: Liver iron overload and C282Y mutation are associated with a higher risk of HCC in patients with alcoholic but not HCV-related cirrhosis.

Abbreviations used in this paper: AFP, α-fetoprotein, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, SVR, sustained virologic response