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

Hepatology Communications 9(3):e0657, March 2025. | DOI: 10.1097/HC9.0000000000000657

Hepatic abnormalities, usually mild, are common in protoporphyrias (EPP/XLP). In a minority of cases, however, severe hepatopathy occurs. Liver disease remains a significant contributor to morbidity and mortality to individuals with EPP and XLP.

In this publication, a total of 322 individuals with EPP or XLP participating in the NIH-supported Porphyrias Consortium registry were analyzed. Clinical history, laboratory values, and liver histology were compiled and examined. 

Liver chemistry data were available for 235 participants, of which 56% exhibited mostly mild enzyme elevations. Elevated protoporphyrin levels correlated with abnormal liver tests. Eleven patients (3.4%) developed protoporphyric hepatopathy, and a small subset required liver transplantation. Ultimately, 2.5% underwent liver transplant, 1.2% underwent bone marrow transplant, 16.8% had cholecystectomy, and 2.5% died—62.5% of these deaths were directly attributable to liver disease. XLP patients had a higher incidence of liver-related complications compared to those with EPP. 

These findings underscore the need for standardized hepatic screening and long-term monitoring strategies in protoporphyria care. 

Authors

Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine McDonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan McGuire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani; Porphyrias Consortium of the Rare Diseases Clinical Research Network