HEPATIC COMPLICATIONS OF ERYTHROPOIETIC PROTOPORPHYRIA

A quarter of patients with erythropoietic protoporphyria develop mild to severe cholestatic Liver disease. The determination of early indica tors of hepatobiliary involvement are of pivotal importance to select patients for choleretic therapy. Porphyrin parameters were studied dur ing ursodeoxycholic acid treatment in eight patients with protoporphyr in-associated liver disease and eight patients with liver failure befo re and after Liver transplantation. The patients with intrahepatic cho lestasis exhibited excessive protoporphyrinemia (27 mu mol/l) compared with controls (normal <0.64 mu mol/l). Fecal protoporphyrin excretion decreased in patients with deterioration of liver function: whereas u rinary coproporphyrin increased up to 2290 nmol/24 h (normal <119 nmol /24 h). Coproporphyrin isomer I proportion increased to 71+/-10%; ((x) over bar+/-SD, n=8) in patients with terminal liver failure (normal < 31%). During therapy with ursodeoxycholic acid biochemical improvement occurred but without clinical remission in most cases.-Eight patients underwent liver transplantation between 1987 and 1997, One patient di ed of liver failure. Two transplant recipients are in a good condition since 8 and 9 years, respectively. All explanted livers revealed micr onodular cirrhosis and high protoporphyrin levels of about 25,000-fold ((x) over bar, n=3). Immediately after liver transplantation protopor phyrin in erythrocytes decreased to 46-96% of pre-operative values. Co proporphyrin remained moderately elevated due to postoperative cholest asis. A post-operative rise in fecal protoporphyrin elimination reflec ted sufficient biliary clearence of protoporphyrin by the transplant. In conclusion, moderate coproporphyrinuria with isomer I is the earlie st sign of liver complications in erythropoietic protoporphyria. Progr ession of protoporphyrin induced toxic liver injury is indicated by ex cessive protoporphyrinemia and coproporphyrinuria with an isomer I pro portion >71+/-10%, and reduction of fecal protoporphyrin excretion. Re sults suggest that therapy of intrahepatic cholestasis with ursodeoxyc holic acid is only effective in the initial stages of Liver disease in erythropoietic protoporphyria. In patients with severe cholestatic he patic failure, liver transplantation is the treatment of choice.