Liver involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria

Abstract

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at enrollment was 33.3 years. Liver chemistries were available for 235 patients, and 132 (56.2%) had abnormalities, mostly mild. Abnormal liver enzymes were associated with higher erythrocyte protoporphyrin levels. Eleven patients had advanced protoporphyric hepatopathy. In total, 54 (16.8%) underwent cholecystectomy, 8 (2.5%) had a liver transplant, 4 (1.2%) had a bone marrow transplant, and 8 (2.5%) died. At least 4 deaths were caused by liver failure due to protoporphyric hepatopathy, 2 were complications of bone marrow transplant, and 1 from HCC, which developed in a patient with EPP without cirrhosis. Patients with XLP were more likely to develop liver-related complications compared to EPP.

Conclusions: Liver abnormalities are common in patients with EPP and XLP. In this national registry, only 3.4% had protoporphyric hepatopathy, with most requiring a transplant. Of the deaths, 62.5% were attributable to liver disease. Further observations are needed for guiding hepatic evaluation and management of patients with protoporphyria with or without initial hepatic abnormalities.