Liver disease and erythropoietic protoporphyria: a concise review

Abstract

The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme. In erythropoietic protoporphyria (EPP), in the majority of cases an autosomal dominant disease, there is a mutation of the gene that encodes ferrochelatase (FECH). FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes, plasma, skin and liver. The prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 000. Clinical manifestations of EPP appear in early infancy upon first exposure to the sun. Nevertheless, approximately 5%-20% of patients with EPP develop liver manifestations. Retention of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity, such as cholelithiasis, mild parenchymal liver disease, progressive hepatocellular disease with end-stage liver disease and acute liver failure. Liver damage is the major risk in EPP patients, so surveillance and frequent clinical and biochemical liver follow-up is mandatory. The diagnostic approach consists in detecting increased levels of protoporphyrin, decreased activity of FECH and genetic analysis of the FECH gene. A variety of non-surgical therapeutic approaches have been adopted for the management of EPP associated with liver disease, but none of these has been shown to be unequivocally efficacious. Nevertheless, some may have a place in preparing patients for liver transplantation. Liver transplantation does not correct the constitutional deficiency of FECH. Consequently, there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of protoporphyrin. Some authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

Figure 1

The heme biosynthetic pathway. In erythropoietic protoporphyria there is a deficiency in the activity of ferrochelatase which catalyzes the insertion of the ferrous iron into the protoporphyrin IX ring to form heme.