Title: Occurrence of porphyria cutanea tarda during peginterferon/ribavirin therapy for chronic viral hepatitis C
Abstract: Porphyria cutanea tarda (PCT) is a metabolic disorder characterized by a reduced hepatic activity of uroporphynogen decarboxylase (URO-D), an enzyme of the heme synthesis. The clinical features of PCT may be brought into light by hepatic injury induced by hepatitis C virus (HCV). A significant association between HCV and PCT is well recognized, although the role of HCV in the appearance of PCT is still debated because confounding factors often coexist, such as alcohol, other viruses, drugs or iron overload ([1]Gisbert J.P. Garcia-Buey L. Pajares J.M. Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis.J Hepatol. 2003; 39: 620-627Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). HCV therapy may improve PCT although PCT was rarely reported as a de novo occurrence during an interferon/ribavirin therapy (Jessner et al. Hepatology 2002;36:1301–1302); here, we describe two such other cases. Porphyria cutanea tarda (PCT) is a metabolic disorder characterized by a reduced hepatic activity of uroporphynogen decarboxylase (URO-D), an enzyme of the heme synthesis. The clinical features of PCT may be brought into light by hepatic injury induced by hepatitis C virus (HCV). A significant association between HCV and PCT is well recognized, although the role of HCV in the appearance of PCT is still debated because confounding factors often coexist, such as alcohol, other viruses, drugs or iron overload ([1]Gisbert J.P. Garcia-Buey L. Pajares J.M. Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis.J Hepatol. 2003; 39: 620-627Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). HCV therapy may improve PCT although PCT was rarely reported as a de novo occurrence during an interferon/ribavirin therapy (Jessner et al. Hepatology 2002;36:1301–1302); here, we describe two such other cases. First case. Chronic hepatitis C (genotype 1a) was diagnosed in a 34-year-old man with a past history of alcoholism and drug addiction. Family history was noncontributory and he had no past medical history of cutaneous disease. He was treated with sertraline in combination to buprenorphine. Liver biopsy examination showed active chronic hepatitis (METAVIR score A2F2). Laboratory data revealed elevated transaminase levels (AST 82 IU/l and ALT 104 IU/l), ferritin 2408 ng/ml (ULN 150). Tests for hemochromatosis (C282Y and H63D), hepatitis B and HIV were negative. Treatment by peginterferon-α2b (1.5 μg/kg/wk) plus ribavirin (1000 mg/day) was administered between July 2003 and July 2004 with a viral clearance at the end of treatment. In August 2003, he presented vesicles and erosions on the hands consistent with PCT (skin biopsy) and confirmed by the elevated urinary uroporphyrin level (343 g/day; N<25). A blood alcohol level dosed at this moment was negative. PCT was treated with chloroquine 200 mg twice weekly, allowing progressive regression of skin lesions. Second case. A 47-year-old man harbored a chronic hepatitis C (genotype 1b, METAVIR score A2F3 with a mild iron deposition in Kupffer cells). He consumed more than 40 g alcohol daily from 1985 to 2001. His family history was negative and he had no past medical history of cutaneous disease. His body weight was 100 kg and his height 187 cm. At presentation, ALT and AST were between 2 and 3 ULN and ferritin was 800 ng/ml (ULN 150). Other assays excluded hemochromatosis (C282Y and H63D) and autoimmune liver diseases. Peginterferon-α2b (1.5 μg/kg/wk) plus ribavirin (1200 mg/day) was unsuccessfully administered between September 2003 and January 2004 and a typical clinical PCT was diagnosed on elevated urinary uroporphyrin level (2728 nmol/l; N<50) in November 2003. A complete clinical response of PCT was achieved with repeated phlebotomy. The mechanism whereby HCV trigger PCT remains unclear. In several studies, no alterations in porphyrin metabolism was demonstrated in HCV-positive patients without PCT [[3]O'Reilly F.M. Darby C. Fogarty J. et al.Porphyrin metabolism in hepatitis C infection.Photodermatol Photoimmunol Photomed. 1996; 12: 31-33Crossref PubMed Scopus (31) Google Scholar], suggesting a triggering effect of HCV infection in genetically predisposed patients. In contrast, other studies demonstrated that HCV infection induces a decreased concentration of URO-D, even in patients without PCT. Improvement of PCT during HCV therapy was well recognized [[4]Sheikh M.Y. Wright R.A. Burruss J.B. Dramatic resolution of skin lesions associated with porphyria cutanea tarda after interferon-alfa therapy in a case of chronic hepatitis C.Dig Dis Sci. 1998; 43: 529-533Crossref PubMed Scopus (60) Google Scholar], but recently, Jessner et al. described an acute flare of PCT on such therapy [[2]Jessner W. Der-Petrossian M. Christiansen L. Maier H. Steindl-Munda P. Gangl A. et al.Porphyria cutanea tarda during interferon/ribavirin therapy for chronic hepatitis C.Hepatology. 2002; 36: 1301-1302Crossref PubMed Scopus (20) Google Scholar]. Our cases confirmed that all situations could be encountered. The striking geographical variation in the association between HCV and PCT suggests that PCT seems to be a multifactor disease caused by an hypothetical interaction between environmental and genetic factors such as genes of iron metabolism and UROD [[5]Fargion S. Fracanzani A.L. Prevalence of hepatitis C virus infection in porphyria cutanea tarda.Hepatology. 2003; 39: 635-638Abstract Full Text Full Text PDF Scopus (20) Google Scholar]. Mild to moderate iron overload is common in patients with chronic hepatitis C and an interaction between iron metabolism genes and HCV was recently suggested [[6]Tung B.Y. Emond M.J. Bronner M.P. Raaka S.D. Cotler S.J. Kowdley K.V. Hepatitis C, iron status, and disease severity: relationship with HFE mutations.Gastroenterology. 2003; 124: 318-326Abstract Full Text PDF PubMed Scopus (139) Google Scholar], because HCV could produce an iron-dependent oxidative process which inactivated the UROD [[5]Fargion S. Fracanzani A.L. Prevalence of hepatitis C virus infection in porphyria cutanea tarda.Hepatology. 2003; 39: 635-638Abstract Full Text Full Text PDF Scopus (20) Google Scholar]. The clinical resolution of PCT after venesection and its relapse with administration of iron demonstrated that hepatic iron plays a key role in the pathogenesis of PCT [[7]Bonkowsky H.L. Poh-Fitzpatrick M. Pimstone N. Obando J. Di Bisceglie A. Tattrie C. et al.Porphyria cutanea tarda, hepatitis C and HFE-1 gene mutations in North America.Hepatology. 1998; 27: 1661-1669Crossref PubMed Scopus (227) Google Scholar]. Ribavirin, which increases the hepatic iron storage owing to haemolysis, could precipitate PCT. This well-known haemolytic side effect of ribavirin has never been emphasized in such circumstances and would deserve probably more attention. Venesection should be performed before initiation of interferon/ribavirin therapy in patients with a past history of PCT and all the potential triggering factor should be excluded to minimize the risk of relapse of PCT.
Publication Year: 2004
Publication Date: 2004-12-15
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 17
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