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Semin Liver Dis 2023; 43(04): 446-459
DOI: 10.1055/s-0043-1776760
Review Article

The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease

Oluwashanu Balogun
1   Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Kari Nejak-Bowen
1   Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
2   Pittsburgh Liver Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
› Author Affiliations Funding This study was funded by the U.S. Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Diseases, NIH grant no. 1R01DK124412 to Kari Nejak-Bowen.
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Abstract

The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight enzymes involved in heme biosynthesis. We also discuss the pathophysiology of the hepatic porphyrias in detail, covering epidemiology, histopathology, diagnosis, and complications. Cellular consequences of porphyrin accumulation are discussed, with an emphasis on oxidative stress, protein aggregation, hepatocellular cancer, and endothelial dysfunction. Finally, we review current therapies to treat and manage symptoms of hepatic porphyria.

Keywords

porphyria - heme - δ-aminolevulinic acid - acute intermittent porphyria - neurovisceral


Publication History

Article published online:
16 November 2023

© 2023. Thieme. All rights reserved.

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