Telehin D. HCV-associated hereditary hemochromatosis and Porphyria cutanea tarda in monozygotic twins.

17th European Congress of Clinical Microbiology and Infectious Diseases, – Munich, – 2007.


We had a unique opportunity to compare a course of HH and PCT in two HCV-infected monozygotic twins. We explored four generation of the twins’ family. One of twins received antiviral therapy (alfa2b-IFN+Rbvn). A persistent remission of PCT and discontinued viremia was achieved. The other one was only given pathogenetic and phlebotomy treatment. The symptoms of CHC and PCT in this case have undulat-ing course. This study showed that HCV-infection is the main trigger of HH and PCT. The management of PCT in HCV-infected patients should include antiviral therapy.

Introduction and Purpose

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of excess iron storage in target organs, such as the liver, heart, and pancreas. Porphyria cutanea tarda (PCT) is a dermatological condition resulting in bullous skin lesions with scarring, hypertrichosis, and pigmentation. It is caused by a defect in the functioning of uroporphyrinogen decarboxylase (URO-D). As the hepatic siderosis of PCT and HH appeared similar, investigators screened PCT patients for the HLA allelic markers. It was postu-lated that there may be a common genetic abnormality that could explain the iron overload in PCT patients. Phenotypic expression PCT can vary widely between siblings suggesting that environmental factors are con-tributory. An important exogenous agent able to initiate latent HH and PCT manifestation is HCV infection. On the other hand, iron overload is associated with increased hepatic fibrosis and decreased efficiency of antiviral therapy. The aim of this study is to investigate a link between inherited factors, phenotypic expression of he-reditary hemochromatosis (HH), porphyria cutanea tarda (PCT) and course of chronic hepatitis C (CHC) and to evaluate the efficiency of antiviral therapy on HCV-associated PCT compared to the course of a similar disease without antiviral treatment.


Clinical, biochemical, histologic, virologic and genetic examination of two HCV-infected monozygotic twins with HH and PCT was performed. Liver sections were stained with routine stains for his-tologic evaluation and with Perls Prussian stain for iron grading. Histologic grading and staging of chronic hepatitis were evaluated according to the score METAVIR using liver biopsy and FibroMax-test. Iron status was determined from transferrin saturation, serum iron, serum ferritin and hepatic iron. Liver metabolism was determined from liver chemistries: alanine aminotransferase, aspartate aminotransferase, total bilirubine and gamma-glutamyl transpeptidase. The degree of porphyrin metabolism disturbance was evaluated according to the concentration of uro- and coproporphyrins in the urine. HCV-RNA and its genotype were detected by a reverse-transcription polymerase chain reaction method (RT-PCR). The twins’ HLA-type was determined by lymphocyte serologic identification method. We explored four generation of the twins’ family and found HH and PCT in the family history suggestive of autosomal recessive inheritance. All patients and control subjects gave informed consent for the study.


Patients O. and A., monozygotic male twins aged 42, while still being infants were simultaneously infected with HCV during hemotransfusion conducted because of tge Rh-conflict and following hemolytic dis-ease. Manifestative forms of acute hepatitis or any other episodes of jaundice (exept hemolytic) were not found in their past history. The first symptoms of the disease appeared 35 years after the infection: marked fatigue, increased skin fragility, epithelial desquamation even in the presence of tiniest injuries, bullons lesions, hyper-trichosis and hyperpigmentation of the face, red colour of the urine. Additional investigations revealed erythro-cytosis, increased colour index, ALT=2N, coproporphyrins in the urine – 7N, uroporphyrins in the urine – 19N, AntiHCV(+), HCV-RNA(+), genotype HCV – 1b, serum iron – 16.3 mcmol/l, ferritin – 219 mcg/l. Liver biopsy: the original architecture of the liver moderately transformed, strands of fibrosis extend out from portal areas but do not interconnect, Perls stain positive – hepatocytes contained fine granular deposits of iron-con-taining pigment. HLA-typing showed HLA-A3 phenotype of twins.

The diagnosis Сhronic hepatitis C, (METAVIR score A2F4) with extrahepatic manifestations: PCT, primary hemochromatosis was established. Genealogic exploration of our probands revealed clinical minifestation of HH and PCT only in the first generation. Considering low cocnordance of monozygotic twins in relation to HH and PCT (40%), it may be assumed that it was HCV-infection, which is an environmental factor, that became the trigger of the latent forms of HH and PCT. One of the twin-brothers was given AVT. A persistent remission of PCT and discontinued viremia was achieved The other one was only given pathogenetic treatment. The symptoms of CHC and PCT in this case have undulating course.


This study may provide additional information about new factors and mechanism that po-tentiate or counteract the effect of the haemochromatosis gene. This case allows to objectively evaluate the effi-ciency of antiviral therapy of CHC in combination with HH and PCT compared to the natural course of a simi-lar disease. The current study showed that HCV-infection probably acts as a main triggering factor of HH and PCT in genetically predisposed subjects. The management of PCT in HCV-infected patients should include antiviral therapy. An association is established between HH, PCT and HLA-A3.