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.

Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress

“…Because Fech mutation is harbored in the bone marrow and liver (as the major heme factories), PP-IX accumulation occurs in both of these tissues. The excess PP-IX from bone marrow is transported in serum by albumin and then taken up by the liver (10). Thus, based on the source of PP-IX, protoporphyria could be classified as extrahepatic (e.g.…”

“…Protoporphyria (both EPP and XLP) is associated with several liver-related complications including cholelithiasis and parenchymal liver disease (in 5-20% of cases) that may be mild or progressive, potentially becoming end-stage (3,4,10). Recently, we demonstrated that the nuclear intermediate filament protein, lamin, aggregates in response to PP-IX-mediated liver damage (11).…”

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

“…Then excessive protoporphyrin IX accumulates in erythrocytes and other tissues like liver and skin (Gouya et al, 2006). EPP is rare, with the incidence ranging from 1/200 000 to 1/75 000 worldwide (Casanova-Gonzalez et al, 2010). The main clinical manifestations include skin photosensitivity, skin burning, itching with subsequent cutaneous signs such as swelling and redness after visible light exposure, while blisters are sparse.…”

Eryhtropoietic Protoporphyria

“…12 As liver transplant does not correct the constitutional deficiency of FECH, there is a risk of recurrence of liver disease even after liver transplant due to continuing overproduction of protoporphyrin. 9 Then, bone marrow transplantation may be considered in liver allograft recipients in the future.…”

“…2,9 Excess PP with any origin is excreted by the liver into bile and enters an enterohepatic circulation. 10 Excess PP becomes insoluble in bile and exerts cholestatic effects, structural changes from mild inflammation to fibrosis and cirrhosis.…”