Hepatitis C und Hämochromatose bei Porphyria cutanea tarda

Zusammenfassung

Die Porphyria cutanea tarda (PCT) ist durch eine verminderte Aktivität des Enzyms Uroporphyrin-Decarboxylase (URO-D) mit konsekutiver toxischer Akkumulation von Uro- und Heptaporphyrinen in der Leber charakterisiert. Neben Alkohol und verschiedenen Arzneistoffen ist die PCT in steigender Prävalenz von Nord- (8 - 10 %) nach Südeuropa (71 - 91 %) mit Antikörpern gegen das Hepatitis-C-Virus (HCV) assoziiert. Die chronische HCV-Infektion wird deshalb als auslösender Faktor der PCT und die PCT als wichtige extrahepatische Manifestation der HCV-Infektion in prädisponierten Individuen angesehen. Bei der PCT findet sich darüber hinaus häufig eine Eisenüberladung, die mit einer Hemmung des Enzyms Uro-D in den Hepatozyten in Zusammenhang gebracht wird. Eisendepletion via Phlebotomie führt zur Remission der Erkrankung. Etwa zwei Drittel der Patienten mit PCT in Sachsen sind Träger der klassischen Hämochromatose (HFE)-Mutationen (C282Y und/oder H63D). Während einfach oder compound-Heterozygotie für eine HFE-Mutation das therapeutische Ansprechen auf Chlorquin bei PTC nicht beeinflussen, sprechen Patienten mit homozygoter Mutation (C282Y/C282Y) bzw. manifester Hämochromatose und PCT schlecht auf eine Chloroquin-Therapie an. Letztere sollten prinzipiell mit Aderlass behandelt werden, um toxisches Eisen zu entfernen.

Summary

Porphyria cutanea tarda (PCT) is characterized by decreased activity of the enzyme uroporphyrinogen decarboxylase (URO-D) and the accumulation of uro- and heptaporphyrins in the liver. Apart from increased alcohol exposure and certain drugs, PCT is associated with antibodies to the hepatitis C virus (HCV), with its prevalence increasing from Northern (8-10%) to Southern Europe (71 to 91%). Chronic HCV-infection is thus considered to be a major trigger for PCT and PCT is said to be an important extrahepatic manifestation of HCV-infection in predisposed individuals. Iron overload is common in PCT. Iron is an inhibitory co-factor of URO-D activity in hepatocytes. Accordingly, in support of the critical role of iron, the clinical efficacy of iron removal is coupled to an improvement of hepatic URO-D activities. Up to two thirds of Saxon patients with PCT carry the classical hemochromatosis (HFE) mutations (C282Y and/or H63D). HFE genotyping can help to further classify patients with PCT and associated hemochromatosis. Simple or compound heterozygosity of HFE mutations does not affect the therapeutic response to chloroquine in PCT. Since Patients carrying homzygous mutations (C282Y/C282Y) with hemochromatosis and PCT do not respond to chloroquine, phlebotomy should be first-line treatment to remove toxic iron.

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