Hepatitis C und Hämochromatose bei Porphyria cutanea tarda

Abstract

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 homozygous mutations (C282Y/C282Y) with hemochromatosis and PCT do not respond to chloroquine, phlebotomy should be first-line treatment to remove toxic iron.

Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients

“…1,39 In this study, positive anti-HCV was 41.7% and the majority (84%) presented association with alcoholism. Most of our patients (60%) were diagnosed for HCV infection after the emergence of PCT, hence the need to investigate HCV in these patients.…”

“…1 Clinically it is characterized by skin fragility, hyperpigmentation and blistering affecting photo exposed areas, facial hypertrichosis and laboratory exams indicating iron overload and increased levels of liver enzymes. 2 Diagnosis is based upon clinical manifestations, dosage of 24-hour urinary porphyrins (URO/COPRO > 3:1) and increased fecal levels of isocoproporphyrins (ISOCOPRO) or increase in plasma porphyrins in anuric patients.…”

Sun, iron, alcohol and intrinsic liver disease: a recipe for failure

“…One study suggests that up to two-thirds of patients with PCT have mutations in the HFE gene 19. Accordingly, genetic testing for HFE gene mutations is reasonable for all patients with PCT.…”

Labordiagnostik und Therapie der Porphyrien

“…Alternativ zur Behandlung mit Chloroquin kann auch eine Aderlasstherapie (Phlebotomie) durchgeführt werden, insbesondere bei hohen Eisen-und Ferritin-Spiegeln und Homozygotie für Mutation C282Y im Hämochro-matose-Gen HFE [2,9]. Kürzlich veröffent-lichte Untersuchungsergebnisse weisen darauf hin, dass eine Chloroquinbehandlung bei klinisch manifester PCT und Vorliegen von Mutation C282Y auf beiden Allelen des HFE-Gens unwirksam ist und daher bei diesen Patienten eine Aderlasstherapie zur Reduktion toxischen Eisens bevorzugt zum Einsatz kommen sollte [13,14]. In einzelnen Fällen kann auch eine Kombination der niedrig dosierten Chloroquintherapie mit der Phlebotomie sinnvoll sein.…”