ArticleMolecular medicine (Cambridge, Mass.)2015
Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review.Gastroenterology · 2023Guideline
- Porphyrias: Pathophysiology and clinical management recommendations for hepatologists.Hepatology communications · 2025Review
- Porto-Sinusoidal Vascular Disease in Congenital Erythropoietic Porphyria Needing Liver Transplantation.ACG case reports journal · 2024Article
- Article
- Clinical-Pathological Conference Series from the Medical University of Graz : Case No 175: A 54-year-old man with hyponatremia and delirium after surgery for a prolapsed disc.Wiener klinische Wochenschrift · 2023Article
- Transcriptomic study in explanted liver from a patient with acute intermittent porphyria.JIMD reports · 2023Article
- Recent Insights into the Pathogenesis of Acute Porphyria Attacks and Increasing Hepatic PBGD as an Etiological Treatment.Life (Basel, Switzerland) · 2022Review
- Acute Intermittent Porphyria: Complete Phenotype in a Patient with p.Arg173Trp Variant in Thailand.The American journal of case reports · 2022Article
- Pain in acute hepatic porphyrias: Updates on pathophysiology and management.Frontiers in neurology · 2022Review
- Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for Porphyria-Mediated Hepatocytotoxicity.Toxicologic pathology · 2021Article
- Porphyrias in the Age of Targeted Therapies.Diagnostics (Basel, Switzerland) · 2021Review
- Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers.Cells · 2021Article
- mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks.Molecular therapy. Nucleic acids · 2021Article
- The acute hepatic porphyrias.Translational gastroenterology and hepatology · 2021Review
- Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP.Hematology. American Society of Hematology. Education Program · 2020Article
- Combined Liver and Kidney Transplant in Acute Intermittent Porphyria: A Case Report.The American journal of case reports · 2020Article
- Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management.Current neurology and neuroscience reports · 2020Review
- EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks.Hepatology (Baltimore, Md.) · 2020Observational
- Acute hepatic porphyrias: Current diagnosis & management.Molecular genetics and metabolism · 2019Review
- Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies.Molecular genetics and metabolism · 2019Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Acute intermittent porphyria (AIP) is an autosomal-dominant hepatic disorder caused by the half-normal activity of hydroxymethylbilane (HMB) synthase. Symptomatic individuals experience life-threatening acute neurovisceral attacks that are precipitated by factors that induce the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1), resulting in the marked accumulation of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Here, we provide the first detailed description of the biochemical and pathologic alterations in the explanted liver of an AIP patient who underwent orthotopic liver transplantation (OLT) due to untreatable and debilitating chronic attacks. After OLT, the recipient's plasma and urinary ALA and PBG rapidly normalized, and her attacks immediately stopped. In the explanted liver, (a) ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and ALA and PBG concentrations were increased ~3- and 1,760-fold, respectively; (b) uroporphyrin III concentration was elevated; (c) microsomal heme content was sufficient, and representative cytochrome P450 activities were essentially normal; (d) HMB synthase activity was approximately half-normal (~42%); (e) iron concentration was slightly elevated; and (f) heme oxygenase I mRNA was increased approximately three-fold. Notable pathologic findings included nodular regenerative hyperplasia, previously not reported in AIP livers, and minimal iron deposition, despite the large number of hemin infusions received before OLT. These findings suggest that the neurovisceral symptoms of AIP are not associated with generalized hepatic heme deficiency and support the neurotoxicity of ALA and/or PBG. Additionally, they indicate that substrate inhibition of hepatic HMB synthase activity by PBG is not a pathogenic mechanism in acute attacks.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.