Hepatitis C, porphyria cutanea tarda and liver iron: an update

Authors

  • F. Ryan Caballes,

    1. The Liver-Biliary-Pancreatic Center of Carolinas Medical Center, Charlotte, NC, USA
    2. Department of Medicine, CMC, Charlotte, NC, USA
    Search for more papers by this author
  • Hossein Sendi,

    1. The Liver-Biliary-Pancreatic Center of Carolinas Medical Center, Charlotte, NC, USA
    Search for more papers by this author
  • Herbert L. Bonkovsky

    Corresponding author
    1. Department of Medicine, CMC, Charlotte, NC, USA
    2. Department of Medicine, Universities of CT and NC, Charlotte, NC, USA
    • The Liver-Biliary-Pancreatic Center of Carolinas Medical Center, Charlotte, NC, USA
    Search for more papers by this author

Correspondence

Herbert L. Bonkovsky, Suite 201, Cannon Research Center, 1542 Garden Terrace, Charlotte, NC 28203, USA

Tel: +704 355 3959

Fax: +704 355 7648

e-mail: herbert.bonkovsky@carolinas.org

Abstract

Porphyria cutanea tarda (PCT) is the most common form of porphyria across the world. Unlike other forms of porphyria, which are inborn errors of metabolism, PCT is usually an acquired liver disease caused by exogenous factors, chief among which are excess alcohol intake, iron overload, chronic hepatitis C, oestrogen therapy and cigarette smoking. The pathogenesis of PCT is complex and varied, but hereditary or acquired factors that lead to hepatic iron loading and increased oxidative stress are of central importance. Iron loading is usually only mild or moderate in degree [less than that associated with full-blown haemochromatosis (HFE)] and is usually acquired and/or mutations in HFE. Among acquired factors are excessive alcohol intake and chronic hepatitis C infection, which, like mutations in HFE, decrease hepcidin production by hepatocytes. The decrease in hepcidin leads to increased iron absorption from the gut. In the liver, iron loading and increased oxidative stress leads to the formation of non-porphyrin inhibitor(s) of uroporphyrinogen decarboxylase and to oxidation of porphyrinogens to porphyrins. The treatment of choice of active PCT is iron reduction by phlebotomy and maintenance of a mildly iron-reduced state without anaemia. Low-dose antimalarials (cinchona alkaloids) are also useful as additional therapy or as alternative therapy for active PCT in those without haemochromatosis or chronic hepatitis C. In this review, we provide an update of PCT with special emphasis upon the important role often played by the hepatitis C virus.

Ancillary