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 hydroxymethylbil...
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https://www.riss.kr/link?id=O119696788
C. Schmitt ; H. Lenglet ; A. Yu ; C. Delaby ; A. Benecke ; T. Lefebvre ; P. Letteron ; V. Paradis ; S. Wahlin ; S. Sandberg ; P. Harper ; E. Sardh ; A. K. Sandvik ; J. R. Hov ; A. K. Aarsand ; L. Chiche ; C. Bazille ; J.‐Y. Scoazec ; J. To-Figueras ; M. Carrascal ; J. Abian ; A. Mirmiran ; Z. Karim ; J.‐C. Deybach ; H. Puy ; K. Peoc'h ; H. Manceau ; L. Gouya
2018년
-
0954-6820
1365-2796
SCI;SCIE;SCOPUS
학술저널
78-91 [※수록면이 p5 이하이면, Review, Columns, Editor's Note, Abstract 등일 경우가 있습니다.]
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
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 hydroxymethylbil...
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.
The aim of this study was to determine whether chronic hemin administration contributes to the recurrence of acute attacks.
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.
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.
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.
Benefits and risks of intensive blood-pressure lowering in advanced chronic kidney disease