title: Liver fibrosis in type I Gaucher disease: magnetic resonance imaging, transient elastography and parameters of iron storage.
abstract: Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal storage disorder, include fibrosis and an increased incidence of hepatocellular carcinoma. Splenectomy has been implicated as a risk factor for the development of liver pathology in GD. High ferritin concentrations are a feature of GD and iron storage in Gaucher cells has been described, but iron storage in the liver in relation to liver fibrosis has not been studied. Alternatively, iron storage in GD may be the result of iron supplementation therapy or regular blood transfusions in patients with severe cytopenia. In this pilot study, comprising 14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy controls, we demonstrate that liver stiffness values, measured by Transient Elastography and MR-Elastography, are significantly higher in splenectomized GD patients when compared with non-splenectomized GD patients (p = 0.03 and p = 0.01, respectively). Liver iron concentration was elevated (>60±30 µmol/g) in 4 GD patients of whom 3 were splenectomized. No relationship was found between liver stiffness and liver iron concentration. HFE gene mutations were more frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p = 0.10). Liver disease appeared more advanced in splenectomized than in non-splenectomized patients. We hypothesize a relationship with excessive hepatic iron accumulation in splenectomized patients. We recommend that all splenectomized patients, especially those with evidence of substantial liver fibrosis undergo regular screening for HCC, according to current guidelines.
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anneloes E
authors.initials: AE
authors.lastname: Bohte
authors.forename: Laura
authors.initials: L
authors.lastname: van Dussen
authors.forename: Erik M
authors.initials: EM
authors.lastname: Akkerman
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.forename: Ralph
authors.initials: R
authors.lastname: Sinkus
authors.forename: Peter L M
authors.initials: PL
authors.lastname: Jansen
authors.forename: Jaap
authors.initials: J
authors.lastname: Stoker
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D054459:Elasticity Imaging Techniques; D005260:Female; D005776:Gaucher Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D006801:Humans; D015994:Incidence; D007501:Iron / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011859:Radiography; D013156:Splenectomy
chemical_list: D007501:Iron
references.citation: Clin Gastroenterol Hepatol. 2007 Oct;5(10):1207-1213.e2
references.pmid: 17916548
references.citation: Ann N Y Acad Sci. 2005;1054:379-85
references.pmid: 16339686
references.citation: Blood. 1998 Apr 15;91(8):3085-7
references.pmid: 9531624
references.citation: Br Med J (Clin Res Ed). 1983 Jun 11;286(6381):1864
references.pmid: 6407607
references.citation: Gastroenterology. 2012 May;142(6):1293-1302.e4
references.pmid: 22537436
references.citation: Hepatology. 2012 Jul;56(1):239-47
references.pmid: 22278368
references.citation: Gastroenterology. 2008 Jul;135(1):32-40
references.pmid: 18471441
references.citation: Lancet. 2000 Apr 29;355(9214):1481-5
references.pmid: 10801168
references.citation: Blood. 1997 Jul 1;90(1):43-8
references.pmid: 9207436
references.citation: Hepatology. 2009 Apr;49(4):1083-9
references.pmid: 19140221
references.citation: Pediatrics. 2002 Jun;109(6):1170-3
references.pmid: 12042560
references.citation: Blood Cells Mol Dis. 2005 May-Jun;34(3):197-200
references.pmid: 15885601
references.citation: Am J Med. 1967 Jun;42(6):891-8
references.pmid: 6067457
references.citation: Dis Markers. 2011;31(3):147-54
references.pmid: 22045400
references.citation: Br J Haematol. 2007 Sep;138(6):676-86
references.pmid: 17655728
references.citation: Ann Intern Med. 1995 Jan 1;122(1):33-9
references.pmid: 7985893
references.citation: Am J Hematol. 2009 Apr;84(4):208-14
references.pmid: 19260119
references.citation: J Hepatol. 2010 Jul;53(1):3-22
references.pmid: 20471131
references.citation: Leber Magen Darm. 1991 May;21(3):126, 129-30
references.pmid: 1651436
references.citation: Lancet. 2004 Jan 31;363(9406):357-62
references.pmid: 15070565
references.citation: J Hepatol. 2011 Apr;54(4):650-9
references.pmid: 21146892
references.citation: Magn Reson Med. 2007 Dec;58(6):1135-44
references.pmid: 17969009
references.citation: Br J Haematol. 2004 Mar;124(6):696
references.pmid: 15009056
references.citation: N Engl J Med. 1974 Nov 7;291(19):989-93
references.pmid: 4415565
references.citation: Semin Liver Dis. 2005;25(2):226-9
references.pmid: 15918150
references.citation: Hepatology. 2011 Jul;54(1):328-43
references.pmid: 21452290
references.citation: Haematologica. 2008 Jul;93(7):1119-20
references.pmid: 18519519
references.citation: Am J Hematol. 1985 Apr;18(4):381-4
references.pmid: 3872064
references.citation: Br J Haematol. 2012 Aug;158(4):528-38
references.pmid: 22640238
references.citation: Mt Sinai J Med. 1970 Jul-Aug;37(4):404-17
references.pmid: 4194895
references.citation: J Biol Chem. 1998 Oct 2;273(40):25680-5
references.pmid: 9748235
references.citation: J Hepatol. 2012 Apr;56(4):908-43
references.pmid: 22424438
references.citation: QJM. 2000 Apr;93(4):237-44
references.pmid: 10787452
references.citation: Hepatology. 2013 Mar;57(3):1182-91
references.pmid: 22899556
references.citation: Hum Genet. 1999 Jul-Aug;105(1-2):151-6
references.pmid: 10480370
references.citation: Blood. 2005 Jan 15;105(2):855-61
references.pmid: 15256427
references.citation: Hepatology. 2010 Mar;51(3):828-35
references.pmid: 20063276
references.citation: Blood. 2005 Aug 15;106(4):1460-5
references.pmid: 15860670
references.citation: J Inherit Metab Dis. 2008 Jun;31(3):319-36
references.pmid: 18509745
references.citation: Arch Pathol Lab Med. 1982 Aug;106(8):388-91
references.pmid: 7049116
references.citation: Ann Oncol. 1999 Feb;10(2):243
references.pmid: 10093697
references.citation: Clin Chim Acta. 2007 Jun;381(2):136-9
references.pmid: 17408605
references.citation: J Biol Chem. 2003 Oct 17;278(42):40911-6
references.pmid: 12890686
references.citation: Medicine (Baltimore). 2011 Jan;90(1):52-60
references.pmid: 21200186
references.citation: Clin Orthop Relat Res. 1999 May;(362):201-7
references.pmid: 10335299
references.citation: Liver Int. 2012 Feb;32 Suppl 1:2-8
references.pmid: 22212565
references.citation: Acta Haematol. 1967;37(4):189-97
references.pmid: 4961851
references.citation: Blood Cells Mol Dis. 2006 Jan-Feb;36(1):53-8
references.pmid: 16246599
references.citation: Ultrasound Med Biol. 2003 Dec;29(12):1705-13
references.pmid: 14698338
references.citation: Hepatology. 1986 Jan-Feb;6(1):24-9
references.pmid: 3943787
references.citation: Prog Clin Biol Res. 1982;95:177-217
references.pmid: 7122634
references.citation: Gastroenterology. 1998 Oct;115(4):929-36
references.pmid: 9753496
references.citation: Gastroenterology. 2005 Feb;128(2):343-50
references.pmid: 15685546
references.citation: Ann Intern Med. 1960 Aug;53:293-305
references.pmid: 14418257