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Dtsch Med Wochenschr 2006; 131(13): 691-695
DOI: 10.1055/s-2006-933718
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Hepatologie
© Georg Thieme Verlag Stuttgart · New York

Hepatitis C und Hämochromatose bei Porphyria cutanea tarda

Hepatitis C, hemochromatosis and porphyria cutanea tardaA. Teubner1 , M. Richter1 , D. Schuppan2 , E. Köstler3 , U. Stölzel1
  • 1Sächsisches Porphyriezentrum, Medizinische Klinik II (Gastroenterologie, Hepatologie, Diabetes und Stoffwechsel, Endokrinologie, Infektiologie und Reisemedizin, Onkologie und Internistische Intensivmedizin), Klinikum Chemnitz
  • 2Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
  • 3Sächsisches Porphyriezentrum, Hautklinik, Krankenhaus Dresden - Friedrichstadt
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Publication History

eingereicht: 3.8.2005

akzeptiert: 24.2.2006

Publication Date:
23 March 2006 (online)

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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.

Literatur

  • 1 Bednar B, Kordac V. Changes in the Liver in Porphyria Cutanea Tarda.  Cesk Patol. 1982;  18 219-230
    Search in Google Scholar
  • 2 Beutler E. Penetrance of Haemochromatosis.  Gut. 2003;  52 610-611
    Search in Google Scholar
  • 3 Bonkovsky H L, Banner B F, Lambrecht R W, Rubin R B. Iron in Liver Diseases Other Than Hemochromatosis.  Semin Liver Dis. 1996;  16 65-82
    Search in Google Scholar
  • 4 Bonkovsky H L, Poh-Fitzpatrick M, Pimstone N. et al . Porphyria Cutanea Tarda, Hepatitis C, and HFE Gene Mutations in North America.  Hepatology. 1998;  27 1661-1669
    Search in Google Scholar
  • 5 Brudieux E, de Ledighen V, Moran M J. et al . Hepatic Porphyrin Concentration and Uroporphyrinogen Decarboxylase Activity in Hepatitis C Virus Infection.  J Viral Hepat. 2001;  8 41-47
    Search in Google Scholar
  • 6 Chlumska A, Chlumsky J, Malina L. Liver Changes in Porphyria Cutanea Tarda Patients Treated With Chloroquine.  Br J Dermatol. 1980;  102 261-266
    Search in Google Scholar
  • 7 Clemmensen O, Thomsen K. Porphyria Cutanea Tarda and Systemic Lupus Erythematosus.  Arch Dermatol. 1982;  118 160-162
    Search in Google Scholar
  • 8 Cortes J M, Oliva H, Paradinas F J, Hernandez-Guio C. The Pathology of the Liver in Porphyria Cutanea Tarda.  Histopathology. 1980;  4 471-485
    Search in Google Scholar
  • 9 de Verneuil H, Aitken G, Nordmann Y. Familial and Sporadic Porphyria Cutanea: Two Different Diseases.  Hum Genet. 1978;  44 145-151
    Search in Google Scholar
  • 10 Di Padova C, Marchesi L, Cainelli T. et al . Effects of Phlebotomy on Urinary Porphyrin Pattern and Liver Histology in Patients With Porphyria Cutanea Tarda.  Am J Med Sci. 1983;  285 2-12
    Search in Google Scholar
  • 11 Doss M. Porphyrin Analysis From Liver Cylinders in Late Cutaneous Porphyria.  Klin Wochenschr. 1969;  47 1280-1282
    Search in Google Scholar
  • 12 Doss M. Porphyrins in Liver and Urine in Porphyria Cutanea Tarda.  Dtsch Med Wochenschr. 1970;  95 959-960
    Search in Google Scholar
  • 13 Doss M. Pathobiochemical Transition of Secondary Coproporphyrinuria to Chronic Hepatic Porphyria in Humans.  Klin Wochenschr. 1980;  58 141-148
    Search in Google Scholar
  • 14 Doss M. Hepatic porphyrias: Pathobiochemical, diagnostic, and therapeutic implications. New York. Grune and Stratton Popper, H and Schaffner F, eds. Progress in liver diseases 1982: 573-597
    Search in Google Scholar
  • 15 Doss M, Meinhof W. Differentiation of Hepatic Porphyrinurias.  Dtsch Med Wochenschr. 1971;  96 1006-1013
    Search in Google Scholar
  • 16 Drobacheff C, Derancourt C, Van Landuyt H. et al . Porphyria Cutanea Tarda Associated With Human Immunodeficiency Virus Infection.  Eur J Dermatol. 1998;  8 492-496
    Search in Google Scholar
  • 17 Elder G H. Porphyria Cutanea Tarda.  Semin Liver Dis. 1998;  18 67-75
    Search in Google Scholar
  • 18 Elder G H, Worwood M. Mutations in the Hemochromatosis Gene, Porphyria Cutanea Tarda, and Iron Overload.  Hepatology. 1998;  27 289-291
    Search in Google Scholar
  • 19 Fakan F, Chlumska A, Malina L. Needle-Like Inclusions in Liver Cells Are Specific Diagnostic Signs of Porphyria Cutanea Tarda.  Vnitr Lek. 1998;  44 418-422
    Search in Google Scholar
  • 20 Fargion S, Fracanzani A L, Romano R. et al . Genetic Hemochromatosis in Italian Patients With Porphyria Cutanea Tarda: Possible Explanation for Iron Overload.  J Hepatol. 1996;  24 564-569
    Search in Google Scholar
  • 21 Fargion S, Piperno A, Cappellini M D. et al . Hepatitis C Virus and Porphyria Cutanea Tarda: Evidence of a Strong Association.  Hepatology. 1992;  16 1322-1326
    Search in Google Scholar
  • 22 Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L. Insulin Resistance Is a Cause of Steatosis and Fibrosis Progression in Chronic Hepatitis C.  Gut. 2005;  54 1003-1008
    Search in Google Scholar
  • 23 Fernandez I, Castellano G, De Salamanca R E. et al . Porphyria Cutanea Tarda As a Predictor of Poor Response to Interferon Alfa Therapy in Chronic Hepatitis C.  Scand J Gastroenterol. 2003;  38 314-319
    Search in Google Scholar
  • 24 Ferri C, Baicchi U, la Civita L. et al . Hepatitis C Virus-Related Autoimmunity in Patients With Porphyria Cutanea Tarda.  Eur J Clin Invest. 1993;  23 851-855
    Search in Google Scholar
  • 25 Fracanzani A L, Fargion S, Stazi M A. et al . Association Between Heterozygosity for HFE Gene Mutations and Hepatitis Viruses in Hepatocellular Carcinoma.  Blood Cells Mol Dis. 2005;  35 27-32
    Search in Google Scholar
  • 26 Freesemann A, Frank M, Sieg I, Doss M O. Treatment of Porphyria Cutanea Tarda by the Effect of Chloroquine on the Liver.  Skin Pharmacol. 1995;  8 156-161
    Search in Google Scholar
  • 27 Ippen H. Treatment of Porphyria Cutanea Tarda by Phlebotomy.  Semin Hematol. 1977;  14 253-259
    Search in Google Scholar
  • 28 Kordac V, Semradova M. Treatment of Porphyria Cutanea Tarda With Chloroquine.  Br J Dermatol. 1974;  90 95-100
    Search in Google Scholar
  • 29 Kostler E, Doss M O. Porphyria Cutanea Tarda (Chronic Hepatic Porphyria).  Dtsch Med Wochenschr. 1995;  120 1405-1410
    Search in Google Scholar
  • 30 Kostler E, Gebhardt B, Seebacher C. The HLA System and Porphyria Cutanea Tarda.  Dtsch Z Verdau Stoffwechselkr. 1984;  44 95-100
    Search in Google Scholar
  • 31 Kostler E, Heinicke H J, Schneider F, Riedel H, Hensel J. Porphyria Cutanea Tarda and Lupus Erythematosus.  Z Gesamte Inn Med. 1989;  44 527-529
    Search in Google Scholar
  • 32 Kostler E, Seebacher C, Riedel H, Kemmer C. Therapeutic and Pathogenetic Aspects of Porphyria Cutanea Tarda.  Hautarzt. 1986;  37 210-216
    Search in Google Scholar
  • 33 Kushner J P, Barbuto A J, Lee G R. An Inherited Enzymatic Defect in Porphyria Cutanea Tarda: Decreased Uroporphyrinogen Decarboxylase Activity.  J Clin Invest. 1976;  58 1089-1097
    Search in Google Scholar
  • 34 Lefkowitch J H, Grossman M E. Hepatic Pathology in Porphyria Cutanea Tarda.  Liver. 1983;  3 19-29
    Search in Google Scholar
  • 35 Moran M J, Fontanellas A, Brudieux E. et al . Hepatic Uroporphyrinogen Decarboxylase Activity in Porphyria Cutanea Tarda Patients: the Influence of Virus C Infection.  Hepatology. 1998;  27 584-589
    Search in Google Scholar
  • 36 Okano J, Horie Y, Kawasaki H, Kondo M. Interferon Treatment of Porphyria Cutanea Tarda Associated With Chronic Hepatitis Type C.  Hepatogastroenterology. 1997;  44 525-528
    Search in Google Scholar
  • 37 Phillips J D, Jackson L K, Bunting M. et al . A Mouse Model of Familial Porphyria Cutanea Tarda.  Proc Natl Acad Sci U S A. 2001;  98 259-264
    Search in Google Scholar
  • 38 Pietrangelo A. Hereditary Hemochromatosis - a New Look at an Old Disease.  N Engl J Med. 2004;  350 2383-2397
    Search in Google Scholar
  • 39 Sampietro M, Fracanzani A L, Corbetta N. et al . High Prevalence of Hepatitis C Virus Type 1b in Italian Patients With Porphyria Cutanea Tarda.  Ital J Gastroenterol Hepatol. 1997;  29 543-547
    Search in Google Scholar
  • 40 Sanchez-Tapias J M. Nosocomial Transmission of Hepatitis C Virus.  J Hepatol. 1999;  31 (Suppl 1) 107-112
    Search in Google Scholar
  • 41 Schuppan D, Krebs A, Bauer M, Hahn E G. Hepatitis C and Liver Fibrosis.  Cell Death Differ. 2003;  10 (Suppl 1) S59-S67
    Search in Google Scholar
  • 42 Shan Y, Lambrecht R W, Bonkovsky H L. Association of Hepatitis C Virus Infection With Serum Iron Status: Analysis of Data From the Third National Health and Nutrition Examination Survey.  Clin Infect Dis. 2005;  40 834-841
    Search in Google Scholar
  • 43 Sheikh M Y, Wright R A, Burruss J B. Dramatic Resolution of Skin Lesions Associated With Porphyria Cutanea Tarda After Interferon-Alpha Therapy in a Case of Chronic Hepatitis C.  Dig Dis Sci. 1998;  43 529-533
    Search in Google Scholar
  • 44 Siersema P D, Rademakers L H, Cleton M I. et al . The Difference in Liver Pathology Between Sporadic and Familial Forms of Porphyria Cutanea Tarda: the Role of Iron.  J Hepatol. 1995;  23 259-267
    Search in Google Scholar
  • 45 Sinclair P R, Gorman N, Trask H W. et al . Uroporphyria Caused by Ethanol in Hfe(-/-) Mice As a Model for Porphyria Cutanea Tarda.  Hepatology. 2003;  37 351-358
    Search in Google Scholar
  • 46 Stolzel U, Kostler E, Koszka C. et al . Low Prevalence of Hepatitis C Virus Infection in Porphyria Cutanea Tarda in Germany.  Hepatology. 1995;  21 1500-1503
    Search in Google Scholar
  • 47 Stolzel U, Kostler E, Schuppan D. et al . Hemochromatosis (HFE) Gene Mutations and Response to Chloroquine in Porphyria Cutanea Tarda.  Arch Dermatol. 2003;  139 309-313
    Search in Google Scholar
  • 48 Stolzel U, Schuppan D, Tillmann H L. et al . Autoimmunity and HCV Infection in Porphyria Cutanea Tarda: a Controlled Study.  Cell Mol Biol (Noisy -le-grand). 2002;  48 43-47
    Search in Google Scholar
  • 49 Thevenot T, Bachmeyer C, Hammi R, Dumouchel P, Ducamp-Posak I, Cadranel J F. Occurrence of Porphyria Cutanea Tarda During Peginterferon/Ribavirin Therapy for Chronic Viral Hepatitis C.  J Hepatol. 2005;  42 607-608
    Search in Google Scholar
  • 50 Uthemann H, Kotitschke R, Lissner R, Goerz G. Serologic Hepatitis B Markers in Porphyria Cutanea Tarda.  Dtsch Med Wochenschr. 1980;  105 1718-1720
    Search in Google Scholar
  • 51 Valls V, Ena J, Enriquez-De-Salamanca R. Low-Dose Oral Chloroquine in Patients With Porphyria Cutanea Tarda and Low-Moderate Iron Overload.  J Dermatol Sci. 1994;  7 169-175
    Search in Google Scholar

Prof. Dr. med. Ulrich Stölzel

Sächsisches Porphyriezentrum, Medizinische Klinik II, Gastroenterologie, Hepatologie, Diabetes und Stoffwechsel, Endokrinologie, Infektiologie und Reisemedizin, Onkologie und Internistische Intensivmedizin, Klinikum Chemnitz GmbH, WHO Teaching Project, Akademisches Lehrkrankenhaus der Universitäten Leipzig und Dresden

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