Porphyria cutanea tarda (PCT) arises from a deficiency of uroporphyrinogen decarboxylase (UROD) in the liver. Several exogenous risk factors are associated with the acquired form of the disease. In Southern Europe, PCT is strongly linked to hepatitis C virus (HCV) infection to the point that a high prevalence of viral infection in some geographic areas generated an increase of PCT cases as a complication. In spite of the association, PCT is a rare complication of HCV infection, thus suggesting the existence of susceptibility factors operating in only some patients. Investigation of liver specimens of PCT patients showed iron accumulation, which albeit moderate, was higher in comparison with HCV-infected patients without PCT. Measurements of hepcidin in serum of HCV-infected patients with and without PCT and calculation of hepcidin/ferritin ratio were compatible with the hypothesis that HCV induced inadequate response of hepcidin to iron accumulation. Administration of direct-acting antivirals (DAA) to HCV-infected patients with active PCT showed that eradication of the virus was followed by resolution of PCT and rapid disappearance of urinary porphyrins. This suggests a direct participation of the virus in the oxidative mechanism leading to UROD inhibition. If clinical evolution of HCV- PCT-patients is placed within a time-frame, rapid PCT resolution by DAA is in striking contrast with a long-delay (in most cases of decades) between viral infection and appearance of overt porphyria. 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. Thus, only when iron accumulation reached a threshold, inhibition of UROD attained a critical level. However, the enigma is why only a minority of HCV-infected patients develop PCT. If additional risk factors (i.e. alcohol abuse) are not concurring, it should be concluded that modifier genes or epigenetic mechanisms related to iron homeostasis, facilitate iron progressive accumulation in only a minority susceptible patients.

中文翻译：

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丙型肝炎病毒和皮肤卟啉卟啉菌之间的关联。

皮肤卟啉卟啉菌（PCT）起因于肝脏中尿卟啉原脱羧酶（UROD）的缺乏。几种外源性危险因素与该疾病的获得性形式有关。在南欧，PCT与丙型肝炎病毒（HCV）感染密切相关，以致在某些地理区域病毒感染的高发导致PCT病例增加。尽管存在这种联系，但PCT是HCV感染的罕见并发症，因此表明仅在某些患者中存在易感因素。对PCT患者肝脏标本的调查显示，铁的蓄积虽然不多，但与HCV感染的无PCT的患者相比是较高的。在有和没有PCT的HCV感染患者中，血清中hepcidin的测定以及hepcidin / ferritin比率的计算均与HCV诱导hepcidin对铁蓄积的反应不足的假设相吻合。对具有活性PCT的HCV感染患者施用直接作用抗病毒药物（DAA）表明，根除该病毒后，PCT消退，尿卟啉迅速消失。这表明病毒直接参与了导致UROD抑制的氧化机制。如果将HCV-PCT患者的临床进展放在某个时间范围内，则DAA迅速解决PCT与病毒感染和明显的卟啉症出现之间的长时延（在大多数情况下是数十年）形成了鲜明的对比。如果HCV感染（a）可以解释：增强了UROD附近的氧化环境；（b）：通过肝素下调促进了铁的积累。因此，仅当铁积累达到阈值时，对UROD的抑制才达到临界水平。但是，这就是为什么只有少数HCV感染患者会出现PCT的原因。如果没有其他危险因素（即酗酒），则应得出结论，与铁稳态相关的修饰基因或表观遗传机制仅促进少数易感患者铁逐渐积累。