Hepatobiliary implications and complications in protoporphyria, a 20-year study.

Clinical and biochemical findings in 55 patients with protoporphyria are presented in a 20-year study. The patients revealed a history of photosensitivity, but in 6 cases the diagnosis was not established until a liver abnormality appeared. Protoporphyrin was elevated in erythrocytes and plasma, and also in the feces of most patients. Signs of impaired liver function were observed in 19 patients (35%), also males predominated in this group 72%. Seven subjects (13%) suffered from liver cirrhosis. A female, aged 20, and a male, aged 22, died from fatal liver disease. Erythrocyte protoporphyrin levels in protoporphyria patients with liver complications were 38 +/- 8 mumols/L (mean +/- SEM) compared to 13 +/- 2 (p less than 0.001) for those patients without obvious liver involvement. Patients with hepatobiliary involvement exhibited a pathologic coproporphyrinuria (419 +/- 21 nmol/24h; mean +/- SEM) with an increase in the proportion of isomer I ranging between 43 and 91% of the total (normal value below 31%). Protoporphyrin accumulated in hepatic tissues to various degrees depending on the stage of the disease. Our observations suggest that (a) pathologic coproporphyrinuria with an increase in isomer I serves as a sensitive parameter for recognizing subclinical and clinical hepatobiliary disease, (b) liver involvement may occur more frequently than has previously been reported, and (c) that treatment with cholic acids results in biochemical and clinical improvement. The pathogenetic course from the erythropoietic disease to include hepatic involvement develops in phases. Protoporphyria should be designated as erythrohepatic.