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

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 disease. Changes in bile canalicular ultrastructure 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.

Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

“…Accumulation ofprotoporphyrin has been detected as brown pigments in hepatocytes, Kupffer cells and biliary canaliculae. A recent study (29) concluded that ultrastructural changes in the hepatic parenchymal cells are present in early stages ofthe disease. Moreover, biliary canalicular abnormalities responsible for cholestasis were observed, similar to that described in rat livers perfused with protoporphyrin (30).…”

Cloning of murine ferrochelatase.

“…Protoporphyria is an autosomal dominant disease that is characterized biochemically by elevated protoporphyrin levels and clinically by photosensitivity and hepatobiliary disease (18). A rare but severe clinical sequela of protoporphyria is liver failure, leading to orthotopic liver transplantation or death (19)(20)(21).…”

Paralytic Ileus and Liver Failure—An Unusual Presentation of Advanced Erythropoietic Protoporphyria

“…The first was choledocholithiasis, which is a well-known complication of EPP [7,25,31,32]. However, in our patient, the gallbladder had been previously removed.…”