Erythropoietic protoporphyria. An overview with emphasis on the liver.

BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis, causing excess of protoporphyrin in blood, skin, liver and other organs. Protoporphyrin accumulation causes rapidly progressive liver failure in a minority of patients. Many questions concerning liver disease in EPP patients remain to be solved.
METHODS: Review and update of the literature on EPP, protoporphyrin and hepatic involvement.
RESULTS: The protoporphyrin molecule can be excited by absorbing light energy. This causes generation of free radicals and thereby photosensitivity of all tissues exposed to light. In the dark, several other toxic mechanisms have been described: deposition of protoporphyrin crystals in hepatocytes and bile canaliculi, interference with redox systems and, recently, formation of cytotoxic bile. Clinical manifestations of EPP are photosensitivity, insignificant hematological abnormalities and liver disease. The hepatic manifestations of the disease are diverse: mildly disturbed liver enzymes in 20% to fatal hepatic failure in less than 5%. End-stage protoporphyric liver failure and liver transplantation are complicated by severe photosensitivity, hemolysis, abdominal pains and neurological dysfunction. To make liver transplantation a safe procedure, special requirements have been proposed. Long-term survival after liver transplantation for EPP has been documented, but does not cure the disease.