title: Liver pathology and hepatocarcinogenesis in a long-term mouse model of erythropoietic protoporphyria.
abstract: Erythropoietic protoporphyria (EPP) is an inherited disease of haem synthesis caused by a mutation in one of the alleles of the enzyme ferrochelatase. This mutation leads to partial deficiency of the enzyme, resulting in increased concentrations of protoporphyrin (PP) in blood, liver, and faeces. Five to ten per cent of patients with EPP develop severe liver disease characterized by the presence of PP deposits. This study used histochemistry and immunohistochemistry to investigate the histopathological features present in the livers of 44 mice with a heterozygous or homozygous point mutation in the ferrochelatase gene (fch/+ and fch/fch mice, respectively). Some fch/+ mouse livers showed mixed steatosis and large cell dysplasia. The livers of fch/fch mice showed periportal or septal fibrosis accompanied by an atypical ductular reaction. These findings suggest that the obstruction and damage of a proportion of large and small bile ducts by PP deposits cause an accumulation of PP in the parenchyma, which leads to damage and loss of hepatocytes due to the toxic effects of PP. The classical stages of hepatocarcinogenesis were observed and hepatic progenitor cells appear to be involved in this process. PP acts as the promoting agent and is probably also the initiating agent.
authors.affiliation: Department of Pathology, University Hospitals Leuven, Leuven, Belgium. Louis.Libbrecht@uz.kuleuven.ac.be
authors.forename: Louis
authors.initials: L
authors.lastname: Libbrecht
authors.forename: Leo
authors.initials: L
authors.lastname: Meerman
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Valeer
authors.initials: V
authors.lastname: Desmet
authors.forename: Peter
authors.initials: P
authors.lastname: Jansen
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005294:Ferrochelatase / Q000235:genetics; D005796:Genes; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D017121:Porphyria, Hepatoerythropoietic / Q000235:genetics / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D011524:Protoporphyrins / Q000032:analysis
chemical_list: D011524:Protoporphyrins; D005294:Ferrochelatase