Early involvement of hepatic parenchymal cells in erythrohepatic protoporphyria? An ultrastructural study of patients with and without overt liver disease and the effect of chenodeoxycholic acid treatement

Authors

  • Louk H. P. M. Raedemakers,

    Corresponding author
    1. Department of Histochemistry and Electron Microscopy and Department of Pathology, University of Utrecht and University Hospital Utrecht, 3501 GH Utrecht, The Netherlands
    • University Hospital, Department of Pathology, P.O. Box 85500, 3501 GH Utrecht, The Netherlands
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  • Maud I. Cleton,

    1. Department of Histochemistry and Electron Microscopy and Department of Pathology, University of Utrecht and University Hospital Utrecht, 3501 GH Utrecht, The Netherlands
    Current affiliation:
    1. Department of Chemical Pathology, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
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  • Carole Kooliman,

    1. Department of Histochemistry and Electron Microscopy and Department of Pathology, University of Utrecht and University Hospital Utrecht, 3501 GH Utrecht, The Netherlands
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  • Harold Baart de La Fajlle,

    1. Department of Dermatology, University of Utrecht and University Hospital Utrecht, 3501 GH Utrecht, The Netherlands
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  • Jan van Hattum

    1. Department of Gastroenterology, University of Utrecht and University Hospital Utrecht, 3501 GH Utrecht, The Netherlands
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Abstract

Liver biopsy specimens obtained from two groups of erythrohepatic protoporphyria patients were studied histopathologically and ultrastructurally. Group 1 comprised seven erythrohepatic protoporphyria patients with a normal liver histology; from two patients liver biopsy specimens were available before and after 1 yr of chenodeoxycholic acid treatment. Group 2 consisted of four patients with a history of liver disease and liver histopathology; three patients were observed before and after 1 yr of chenodeoxycholic acid treatment. Liver specimens of nine kidney transplant donors served as controls.

Unlike the morphology at the light microscopic level, the ultrastructure of hepatic parenchymal cells was affected in both groups of erythrohepatic protoporphyria patients. In both groups the nuclei, endoplasmic reticulum, lateral plasma membranes and bile canaliculi were altered. Collagen fibers were frequently present. In addition, in group 2 bile thrombi and intracytoplasmic protoporphyrin crystals were observed. After chenodeoxycholic acid administration, the latter feature had diminished.

It is concluded that (a) in erythrohepatic protoporphyria ultrastructural changes are present in the hepatic parenchymal cells even in early stages of the discase. Changes in bile canalicular ultrstructure suggest a defective hepatic excretory function, probably caused by the toxic effect of protoporphyrin. (b) Chenodeoxycholic acid administration causes no distinct improvement of the ultrastructure of organelles in the hepatic parenchymal cell or the bile canalicular system but may decrease crystalline protoporphyrin deposition in the liver.(HEPATOLOGY 1990;11:449–457.)

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