Porphyria cutanea tarda (PCT) is the most common human porphyria, due to hepatic deficiency of uroporphyrinogen decarboxylase (UROD), which is acquired in the presence of iron overload and various susceptibility factors, such as alcohol abuse, smoking, hepatitis C virus (HCV) infection, HIV infection, iron overload with HFE gene mutations, use of estrogens, and UROD mutation.
This could be explained if HCV infection (a): enhanced an oxidative environment in the vicinity of UROD and (b): facilitated iron accumulation through hepdicin down-regulation.
Acute intermittent porphyria causes kidney injury, whereas medical situations associated with end-stage renal disease, such as porphyrin accumulation, iron overload and hepatitis C, participate in the inhibition of uroporphyrinogen decarboxylase and predispose the individual to porphyria cutanea tarda.
This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.