{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:58:48Z","timestamp":1787313528866,"version":"build-2736575974"},"reference-count":113,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1R01DK124412"],"award-info":[{"award-number":["1R01DK124412"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1055\/s-0043-1776760","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T19:47:35Z","timestamp":1700164055000},"page":"446-459","source":"Crossref","is-referenced-by-count":6,"title":["The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease"],"prefix":"10.1055","volume":"43","author":[{"given":"Oluwashanu","family":"Balogun","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Nejak-Bowen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Pittsburgh Liver Institute, University of Pittsburgh, Pittsburgh, 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liver","volume":"105","author":"M Yamamoto","year":"1982","journal-title":"Biochem Biophys Res Commun"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0006-291X(83)90993-2","article-title":"Translational inhibition by heme of the synthesis of hepatic delta-aminolevulinate synthase in a cell-free system","volume":"115","author":"M Yamamoto","year":"1983","journal-title":"Biochem Biophys Res Commun"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1073\/pnas.67.2.517","article-title":"Induction of -aminolevulinic acid synthetase in chick embryo liver cells in culture","volume":"67","author":"S Sassa","year":"1970","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1042\/BJ20040570","article-title":"Examination of mitochondrial protein targeting of haem synthetic enzymes: in vivo identification of three functional haem-responsive motifs in 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Zhang","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"06","key":"ref39","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"P D Stenson","year":"2017","journal-title":"Hum Genet"},{"issue":"07","key":"ref40","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/003655100300054891","article-title":"The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study","volume":"60","author":"C Andersson","year":"2000","journal-title":"Scand J Clin Lab Invest"},{"issue":"01","key":"ref41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1042\/BJ20082077","article-title":"Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria","volume":"420","author":"R Gill","year":"2009","journal-title":"Biochem J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1182\/asheducation.V2012.1.19.3795678","article-title":"The porphyrias: advances in diagnosis and treatment","author":"M Balwani","year":"2012","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"key":"ref43","first-page":"373","volume-title":"Inherited porphyrias","author":"R J Desnick","year":"2021"},{"issue":"19","key":"ref44","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1073\/pnas.85.19.7049","article-title":"Human uroporphyrinogen III synthase: molecular cloning, nucleotide sequence, and expression of a full-length cDNA","volume":"85","author":"S F Tsai","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"01","key":"ref45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1006\/mgme.1998.2739","article-title":"Congenital erythropoietic porphyria: prolonged high-level expression and correction of the heme biosynthetic defect by retroviral-mediated gene transfer into porphyric and erythroid cells","volume":"65","author":"R Kauppinen","year":"1998","journal-title":"Mol Genet Metab"},{"issue":"02","key":"ref46","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1111\/ijlh.12282","article-title":"Identification of mutations in the uroporphyrinogen III synthase gene in a Thai girl patient with congenital erythropoietic porphyria","volume":"37","author":"W Glomglao","year":"2015","journal-title":"Int J Lab Hematol"},{"issue":"03","key":"ref47","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00105-015-3732-8","article-title":"[Congenital erythropoietic porphyria: an update]","volume":"67","author":"C Wenner","year":"2016","journal-title":"Hautarzt"},{"issue":"03","key":"ref48","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ymgme.2018.12.008","article-title":"Congenital erythropoietic porphyria: recent advances","volume":"128","author":"A L Erwin","year":"2019","journal-title":"Mol Genet Metab"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"748","DOI":"10.2119\/molmed.2010.00258","article-title":"Congenital erythropoietic porphyria: characterization of murine models of the severe common (C73R\/C73R) and later-onset genotypes","volume":"17","author":"D F Bishop","year":"2011","journal-title":"Mol Med"},{"issue":"45","key":"ref50","doi-asserted-by":"crossref","first-page":"18238","DOI":"10.1073\/pnas.1314177110","article-title":"Therapeutic potential of proteasome inhibitors in congenital erythropoietic porphyria","volume":"110","author":"J M Blouin","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"23","key":"ref51","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1093\/emboj\/cdg606","article-title":"Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase","volume":"22","author":"J D Phillips","year":"2003","journal-title":"EMBO J"},{"issue":"12","key":"ref52","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1073\/pnas.0700547104","article-title":"A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda","volume":"104","author":"J D Phillips","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref53","first-page":"2103","volume-title":"The porphyrias","author":"A Kappas","year":"1995"},{"issue":"21","key":"ref54","doi-asserted-by":"crossref","first-page":"9825","DOI":"10.1016\/S0021-9258(18)67589-1","article-title":"Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA","volume":"261","author":"P H Rom\u00e9o","year":"1986","journal-title":"J Biol Chem"},{"issue":"05","key":"ref55","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1172\/JCI112985","article-title":"Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria","volume":"79","author":"H Fujita","year":"1987","journal-title":"J Clin Invest"},{"key":"ref56","volume-title":"Hepatoerythropoietic porphyria","author":"S Rudnick","year":"1993"},{"issue":"03","key":"ref57","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI111039","article-title":"Harderoporphyria: a variant hereditary coproporphyria","volume":"72","author":"Y Nordmann","year":"1983","journal-title":"J Clin Invest"},{"issue":"05","key":"ref58","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1086\/320118","article-title":"Characterization of mutations in the CPO gene in British patients demonstrates absence of genotype-phenotype correlation and identifies relationship between hereditary coproporphyria and harderoporphyria","volume":"68","author":"J Lamoril","year":"2001","journal-title":"Am J Hum Genet"},{"issue":"02","key":"ref59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1023\/A:1005313024076","article-title":"Hepatic porphyrias in children","volume":"20","author":"G H Elder","year":"1997","journal-title":"J Inherit Metab Dis"},{"issue":"40","key":"ref60","doi-asserted-by":"crossref","first-page":"14232","DOI":"10.1073\/pnas.0506557102","article-title":"Structural basis of hereditary coproporphyria","volume":"102","author":"D S Lee","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref61","volume-title":"Hereditary coproporphyria","author":"B Wang","year":"1993"},{"issue":"20","key":"ref62","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1093\/hmg\/ddi342","article-title":"Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria","volume":"14","author":"C Schmitt","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref63","first-page":"123","volume-title":"Conversion of coprotoporphyrinogen to protoheme in higher eukaryotes and bacteria","author":"H Dailey","year":"1990"},{"issue":"04","key":"ref64","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/BF00282829","article-title":"The inherited enzymatic defect in porphyria variegata","volume":"58","author":"J C Deybach","year":"1981","journal-title":"Hum Genet"},{"issue":"10","key":"ref65","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/sj.ejhg.5200860","article-title":"Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients","volume":"10","author":"M von und zu Fraunberg","year":"2002","journal-title":"Eur J Hum Genet"},{"key":"ref66","volume-title":"Variegate porphyria","author":"A K Singal","year":"2013"},{"issue":"7080","key":"ref67","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature04512","article-title":"Mitoferrin is essential for erythroid iron assimilation","volume":"440","author":"G C Shaw","year":"2006","journal-title":"Nature"},{"issue":"05","key":"ref68","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/BF00211026","article-title":"Localization of the human coproporphyrinogen oxidase gene to chromosome band 3q12","volume":"94","author":"V Cacheux","year":"1994","journal-title":"Hum Genet"},{"issue":"06","key":"ref69","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1182\/blood.V93.6.2105.406k28_2105_2110","article-title":"Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation","volume":"93","author":"L Gouya","year":"1999","journal-title":"Blood"},{"issue":"06","key":"ref70","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1086\/301870","article-title":"Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria","volume":"62","author":"U B R\u00fcfenacht","year":"1998","journal-title":"Am J Hum Genet"},{"issue":"06","key":"ref71","first-page":"577","article-title":"Human Gene Mutation Database (HGMD): 2003 update","volume":"21","author":"P D Stenson","year":"2003","journal-title":"Hum Mutat"},{"key":"ref72","volume-title":"Erythropoietic protoporphyria, autosomal recessive","author":"M Balwani","year":"1993"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2147\/CEG.S64283","article-title":"Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease","volume":"7","author":"D G Levitt","year":"2014","journal-title":"Clin Exp Gastroenterol"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2741\/E598","article-title":"The molecular pathogenesis of cholestasis in sepsis","volume":"5","author":"H K Bhogal","year":"2013","journal-title":"Front Biosci (Elite Ed)"},{"issue":"08","key":"ref75","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1172\/JCI42168","article-title":"Organic anion transporting polypeptide 1a\/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs","volume":"120","author":"E van de Steeg","year":"2010","journal-title":"J Clin Invest"},{"issue":"05","key":"ref76","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/j.1582-4934.2010.01098.x","article-title":"Bile acids decrease intracellular bilirubin levels in the cholestatic liver: implications for bile acid-mediated oxidative stress","volume":"15","author":"L Muchova","year":"2011","journal-title":"J Cell Mol Med"},{"key":"ref77","volume-title":"Physiology, bile secretion","author":"M Hundt","year":"2023"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.jpap.2021.100036","article-title":"5-Aminolevulinic acid: a matter of life and caveats","volume":"7","author":"E JH Bechara","year":"2021","journal-title":"J Photochem Photobiol"},{"issue":"5722","key":"ref79","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/280514a0","article-title":"\u03b4-Aminolaevulinic acid is a potent agonist for GABA autoreceptors","volume":"280","author":"M JW Brennan","year":"1979","journal-title":"Nature"},{"issue":"9410","key":"ref80","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0140-6736(04)15646-8","article-title":"Liver transplantation as a cure for acute intermittent porphyria","volume":"363","author":"Z F Soonawalla","year":"2004","journal-title":"Lancet"},{"issue":"02","key":"ref81","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/lt.22345","article-title":"Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis","volume":"18","author":"J K Dowman","year":"2012","journal-title":"Liver Transpl"},{"issue":"05","key":"ref82","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1080\/00365510902935979","article-title":"Clinical aspects of acute intermittent porphyria in northern Sweden: a population-based study","volume":"69","author":"I Bylesj\u00f6","year":"2009","journal-title":"Scand J Clin Lab Invest"},{"issue":"03","key":"ref83","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/joim.12646","article-title":"Acute hepatic porphyria and cancer risk: a nationwide cohort study","volume":"282","author":"C M Baravelli","year":"2017","journal-title":"J Intern Med"},{"issue":"12","key":"ref84","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.amjmed.2014.06.036","article-title":"Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium","volume":"127","author":"H L Bonkovsky","year":"2014","journal-title":"Am J Med"},{"issue":"04","key":"ref85","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1136\/jcp.21.4.501","article-title":"Ultrastructural study of the liver in hepatic porphyria","volume":"21","author":"G Jean","year":"1968","journal-title":"J Clin Pathol"},{"issue":"03","key":"ref86","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ymgme.2019.01.004","article-title":"Porphyria cutanea tarda: recent update","volume":"128","author":"A K Singal","year":"2019","journal-title":"Mol Genet Metab"},{"issue":"04","key":"ref87","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1046\/j.1440-0960.2000.00437.x","article-title":"Porphyria cutanea tarda","volume":"41","author":"N R Bleasel","year":"2000","journal-title":"Australas J Dermatol"},{"key":"ref88","volume-title":"Ala dehydratase deficiency porphyria","author":"G Mohan","year":"2023"},{"issue":"03","key":"ref89","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0891-5849(95)02035-7","article-title":"The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias","volume":"20","author":"M Demasi","year":"1996","journal-title":"Free Radic Biol Med"},{"issue":"04","key":"ref90","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jcmgh.2019.06.006","article-title":"Porphyrin-induced protein oxidation and aggregation as a mechanism of porphyria-associated cell injury","volume":"8","author":"D Maitra","year":"2019","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"05","key":"ref91","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.bbamcr.2011.01.008","article-title":"Control of intracellular heme levels: heme transporters and heme oxygenases","volume":"1813","author":"A A Khan","year":"2011","journal-title":"Biochim Biophys Acta"},{"issue":"06","key":"ref92","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1002\/hep.24324","article-title":"Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection\/sepsis in mice","volume":"53","author":"E H Carchman","year":"2011","journal-title":"Hepatology"},{"issue":"01","key":"ref93","doi-asserted-by":"crossref","first-page":"100778","DOI":"10.1016\/j.jbc.2021.100778","article-title":"Protein-aggregating ability of different protoporphyrin-IX nanostructures is dependent on their oxidation and protein-binding capacity","volume":"297","author":"D Maitra","year":"2021","journal-title":"J Biol Chem"},{"issue":"05","key":"ref94","doi-asserted-by":"crossref","first-page":"512","DOI":"10.2340\/00015555-0870","article-title":"Hepatocellular carcinoma in variegate porphyria: a serious complication","volume":"90","author":"X Schneider-Yin","year":"2010","journal-title":"Acta Derm Venereol"},{"issue":"06","key":"ref95","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0168-8278(00)80097-5","article-title":"Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of occurrence and related factors","volume":"32","author":"C Andant","year":"2000","journal-title":"J Hepatol"},{"issue":"04","key":"ref96","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1600-0781.1997.tb00218.x","article-title":"Porphyria cutanea tarda and hematologic malignancy \u2013 a report of 4 cases","volume":"13","author":"D B McKenna","year":"1997","journal-title":"Photodermatol Photoimmunol Photomed"},{"issue":"09","key":"ref97","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3390\/jcm12093091","article-title":"Intrahepatic cholangiocarcinoma and acute intermittent porphyria: a case report","volume":"12","author":"C C Guida","year":"2023","journal-title":"J Clin Med"},{"issue":"03","key":"ref98","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ymgme.2018.10.001","article-title":"Hepatocellular carcinoma in acute hepatic porphyrias: a Damocles sword","volume":"128","author":"K Peoc'h","year":"2019","journal-title":"Mol Genet Metab"},{"issue":"12","key":"ref99","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/cancers14122947","article-title":"Risk of hepatocellular carcinoma in patients with porphyria: a systematic review","volume":"14","author":"D Ramai","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"05","key":"ref100","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/hep.31460","article-title":"Hepatocellular carcinoma in acute hepatic porphyrias: results from the longitudinal study of the U.S. Porphyrias Consortium","volume":"73","author":"B Saberi","year":"2021","journal-title":"Hepatology"},{"issue":"06","key":"ref101","first-page":"12","article-title":"Endothelial dysfunction in acute hepatic porphyrias","volume":"12","author":"A Ricci","year":"2022","journal-title":"Diagnostics (Basel)"},{"issue":"03","key":"ref102","first-page":"e36058","article-title":"Acute intermittent porphyria's symptoms and management: a narrative review","volume":"15","author":"E Z Kizilaslan","year":"2023","journal-title":"Cureus"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/8904_2015_411","article-title":"Audit of the use of regular haem arginate infusions in patients with acute porphyria to prevent recurrent symptoms","volume":"22","author":"J T Marsden","year":"2015","journal-title":"JIMD Rep"},{"issue":"02","key":"ref104","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jhep.2019.05.003","article-title":"Current and innovative emerging therapies for porphyrias with hepatic involvement","volume":"71","author":"A Fontanellas","year":"2019","journal-title":"J Hepatol"},{"issue":"09","key":"ref105","doi-asserted-by":"crossref","first-page":"801.e19","DOI":"10.1016\/j.amjmed.2006.05.026","article-title":"Open-label study of hemin for acute porphyria: clinical practice implications","volume":"119","author":"K E Anderson","year":"2006","journal-title":"Am J Med"},{"issue":"01","key":"ref106","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/joim.12750","article-title":"Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver","volume":"284","author":"C Schmitt","year":"2018","journal-title":"J Intern 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