dc.date.accessioned | 2019-04-08T10:52:01Z | |
dc.date.available | 2019-04-08T10:52:01Z | |
dc.date.created | 2018-07-13T13:12:42Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Schmitt, Caroline Lenglet, Hugo Yu, Angèle Delaby, Constance Benecke, Arndt Lefebvre, Thibaud Lettéron, Philippe Paradis, Valérie Wahlin, Staffan Sandberg, Sverre Harper, Pauline Sardh, Eliane Sandvik, Arne Kristian Hov, Johannes Espolin Roksund Aarsand, Aasne Karine Chiche, Laurence Bazille, Céline Scoazec, Jean-Yves To-Figueras, Jordi Carrascal, Montserrat Abian, Joaquim Mirmiran, Arienne Karim, Zoubida Deybach, Jean-Charles Puy, Herve Peoc'h, Katell Manceau, Hana Gouya, Laurent . Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. Journal of Internal Medicine. 2018, 284(1), 78-91 | |
dc.identifier.uri | http://hdl.handle.net/10852/67594 | |
dc.description.abstract | Background: Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life‐threatening acute neurovisceral attacks due to the induction of hepatic δ‐aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency. So far, the treatment of choice is hemin which represses ALAS1. The main issue in the medical care of AIP patients is the occurrence of debilitating recurrent attacks.
Objective: The aim of this study was to determine whether chronic hemin administration contributes to the recurrence of acute attacks.
Methods: A follow-up study was conducted between 1974 and 2015 and included 602 French AIP patients, of whom 46 had recurrent AIP. Moreover, we studied the hepatic transcriptome, serum proteome, liver macrophage polarization and oxidative and inflammatory profiles of Hmbs−/− mice chronically treated by hemin and extended the investigations to five explanted livers from recurrent AIP patients.
Results: The introduction of hemin into the pharmacopeia has coincided with a 4.4‐fold increase in the prevalence of chronic patients. Moreover, we showed that both in animal model and in human liver, frequent hemin infusions generate a chronic inflammatory hepatic disease which induces HO1 remotely to hemin treatment and maintains a high ALAS1 level responsible for recurrence.
Conclusion: Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti‐inflammatory therapies should be considered in patients with recurrent AIP. | en_US |
dc.language | EN | |
dc.publisher | Blackwell Science Ltd. | |
dc.title | Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Schmitt, Caroline | |
dc.creator.author | Lenglet, Hugo | |
dc.creator.author | Yu, Angèle | |
dc.creator.author | Delaby, Constance | |
dc.creator.author | Benecke, Arndt | |
dc.creator.author | Lefebvre, Thibaud | |
dc.creator.author | Lettéron, Philippe | |
dc.creator.author | Paradis, Valérie | |
dc.creator.author | Wahlin, Staffan | |
dc.creator.author | Sandberg, Sverre | |
dc.creator.author | Harper, Pauline | |
dc.creator.author | Sardh, Eliane | |
dc.creator.author | Sandvik, Arne Kristian | |
dc.creator.author | Hov, Johannes Espolin Roksund | |
dc.creator.author | Aarsand, Aasne Karine | |
dc.creator.author | Chiche, Laurence | |
dc.creator.author | Bazille, Céline | |
dc.creator.author | Scoazec, Jean-Yves | |
dc.creator.author | To-Figueras, Jordi | |
dc.creator.author | Carrascal, Montserrat | |
dc.creator.author | Abian, Joaquim | |
dc.creator.author | Mirmiran, Arienne | |
dc.creator.author | Karim, Zoubida | |
dc.creator.author | Deybach, Jean-Charles | |
dc.creator.author | Puy, Herve | |
dc.creator.author | Peoc'h, Katell | |
dc.creator.author | Manceau, Hana | |
dc.creator.author | Gouya, Laurent | |
cristin.unitcode | 185,53,48,12 | |
cristin.unitname | Avdeling for transplantasjonsmedisin | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1597130 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Internal Medicine&rft.volume=284&rft.spage=78&rft.date=2018 | |
dc.identifier.jtitle | Journal of Internal Medicine | |
dc.identifier.volume | 284 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | 78 | |
dc.identifier.endpage | 91 | |
dc.identifier.doi | http://dx.doi.org/10.1111/joim.12750 | |
dc.identifier.urn | URN:NBN:no-70774 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0954-6820 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/67594/3/Recurrent%2Battacks%2Bof%2Bacute%2Bhepatic%2Bporphyria.pdf | |
dc.type.version | AcceptedVersion | |