Porphyria Cutanea Tarda, Hepatitis C, Uroporphyrinogen Decarboxylase and Mutations of HFE Gene

Abstract

Background: Hemochromatosis gene (HFE) mutations and the hepatitis C virus (HCV) are known risk factors for porphyria cutanea tarda (PCT), but interactions with erythrocytic uroporphyrinogen decarboxylase (UROD) have seldom been addressed. Objective: In order toexamine the links between these factors, we conducted a multicentre prospective case-control study. Methods: PCT patients with (n = 32) or without HCV (n = 28) were matched to HCV+ (n = 32) and HCV– controls (n = 28). HFE mutations (C282Y and H63D) were analyzed by PCR. Results: PCT+/HCV+ patients were younger than PCT+/HCV– patients (46.9 vs. 58.2 years, p < 0.001). UROD values were not significantly different in HCV+ and HCV– patients. Both C282Y and H63D were more frequent in PCT+ patients than in controls, but there was no difference in HFE genotype according to HCV seropositivity. Mean UROD was lower in case of HFE mutations in both PCT patients and controls. Conclusion: In French patients, HCV infection is probably the major causal factor of PCT. It is not linked with HFE mutations, although they are significantly associated with PCT. A low erythrocytic UROD might be a predisposing factor. The UROD value was lower in patients with HFE mutations, suggesting a possible interaction between HFE genotype and UROD levels.

EASL clinical practice guidelines for HFE hemochromatosis

“…The prevalence of C282Y homozygosity among patients with porphyria cutanea tarda (PCT) was found to be increased significantly compared with control populations, ranging from 9% to 17% in several studies [108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124]. No association between PCT and the C282Y polymorphism was found in Italian patients [125].…”

Porphyria cutanea tarda: an intriguing genetic disease and marker

“…HCV infections and combined HCV and human immunodeficiency virus (HIV) infection have been associated with development of PCT . HCV‐infected individuals develop PCT at an earlier age than do those without the virus . It may be because of a link between PCT and HCV involving the HFE gene mutation H63D and C282Y, which causes an increase in iron overload and leaves those with chronic hepatitis C at risk of hepatocellular injury and fibrosis.…”

Rethinking the Role of Liver Biopsy in the Era of Personalized Medicine

“…This decrease is responsible for increased iron absorption from the gut. The important role that PCT often plays in the hepatitis C virus setting has recently been emphasized [38].…”