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ABSTRACT: Extrahepatic manifestations associated with chronic hepatitis C virus (HCV) infection are increasingly recognized and often complicate HCV therapy. Porphyria cutanea tarda (PCT), an uncommon phenotypic expression of a defect in the uroporphyrinogen decarboxylase enzyme, is 12 times more likely to occur in those with HCV compared with the general population in the United States. It is hypothesized that increased free intrahepatic iron levels and chronic HCV infection can accelerate the pathogenesis of liver injury in patients with phenotypic expression of PCT. Symptomatic treatment of PCT has traditionally revolved around phlebotomy to control total body iron levels. However, phlebotomy for PCT management poses a challenge to concomitant treatment of HCV with combination therapy, ribavirin, and interferon. This article highlights the pathogenesis of PCT and discusses its impact on the management of HCV in individuals with this uncommon extrahepatic disease.Current Hepatitis Reports 04/2012; 4(3):104-111.