title: Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series.
abstract: Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis due to a mutation in the porphobilinogen deaminase gene. The mutation causes a deficiency in the porphobilinogen deaminase enzyme, thereby causing an accumulation of heme precursors (δ-aminolevulinic acid and porphobilinogen). These neurotoxic heme precursors elicit acute neurovisceral attacks, which can be treated with heme-arginate infusions. Some patients require heme-arginate infusions on a regular basis for many years, which ultimately leads to an iron accumulation (increased serum ferritin and iron accumulation in the liver, spleen, and bone marrow on MRI). We report three AIP patients, who developed iron accumulation (with serum ferritin up to 7,850 microgram/liter) due to multiple heme-arginate infusions. We report for the first time that the iron accumulation in these patients was associated with fibrosis on liver histology.
  
  
  CONCLUSIONS
  Regular heme-arginate treatment in AIP does not only lead to increased serum ferritin but may also induce liver fibrosis. This should be taken into account, when weighing the risks and benefits of repeated heme-arginate treatment against the risk and benefits of treating refractory AIP by liver transplantation.
authors.affiliation: Department of Hepatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Willandt
authors.affiliation: Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Nederlands Porphyria Center, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.affiliation: Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Meersseman
authors.affiliation: Department of Gastroenterology, AZ Groeninge, Kortrijk, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: D'Heygere
authors.affiliation: Department of Gastroenterology, AZ Groeninge, Kortrijk, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: George
authors.affiliation: Department of Hepatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.affiliation: Abdominal Transplantation Unit, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Diethard
authors.initials: D
authors.lastname: Monbaliu
authors.affiliation: Department of Hepatology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. david.cassiman@uzleuven.be.|Metabolic Center, University Hospitals Leuven, Leuven, Belgium. david.cassiman@uzleuven.be.
authors.forename: David
authors.initials: D
authors.lastname: Cassiman