Hemochromatose: De rol van aderlating (of bloeddonatie) in de behandeling en opvolging

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1 Hereditary haemochromatosis Hemochromatose: De rol van aderlating (of bloeddonatie) in de behandeling en opvolging David Cassiman

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3 Tf/TIBC Fe 30% Normaal Ferriprivie Chronische inflammatie Hemochromatose

4 IJzerstapeling: genetisch Type I: HFE (C282Y, H63D, S65C) = 95% Type II: juvenile (<30yrs; heart/endocrine) IIa: hemojuvelin (HJV) IIb: hepcidin (HAMP) Type III: transferrin 2 receptor Type IV: ferroportin (AD) IVa: RE cells IVb: hepatocytes (gain-of-function) Aceruloplasminemia

5 Feder JN et al, 1996; Niederau C et al, 1996 Hereditaire Haemochromatose 5 Autosomaal recessief In Europa: 1/200 1/400 Dragerschap 1/10

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7 Hereditaire Haemochromatose Presenterende symptomen: Vermoeidheid Gewrichtspijnen Complicaties Fibrose à cirrhose à hepatocellulair carcinoma Diabetes mellitus Cardiomyopathie Hypothyroidie Absorptie 2-4mg/d (nl. 1-2mg/d) èaccumulatie 1g/jaar Symptomatisch > 20 g (~40-50jr) Later bij vrouwen

8 Hereditaire Haemochromatose Relevantie? Meest prevalente genetische ziekte Asymptomatisch tot levensbedreigend Chronische ziekte Geen gestandardiseerde behandelings en followup strategieën QoL? Health care cost?

9 Low penetrance! Lage penetrantie (5-25%?) Groei, menses, zwangerschap, dieet, bloedverlies, PPI (?) Ethyl, obesitas/nash, virale hepatitis Genetic modifiers (variant in Transferrin)

10 Therapie: aderlatingen 500 ml per week (=250 mg Fe) Tot ferritine µg/l (transferrine saturatie < 45%) Omkeerbaar: gestoorde levertests, pigmentatie, insuline resistentie Niet-omkeerbaar: cirrose, impotentie, gewrichtslijden Daarna onderhoud 2-12 aderlatingen per jaar

11 Hereditaire Haemochromatose Aderlatingen in UZ Leuven: 1500/jr (30/wk) België 11miljoen, 1/200 = HH 50% hyperferritinemie 5 aderlatingen/jr = zakken bloed per jaar 11

12 Nieuwe behandelingsopties Erythrocytapherese 1 vs flebotomie: Verwijderen RBC via aferese = 2.4x meer Fe Kost meer MAAR: minder werkverlet à Netto gelijke kost 1 Rombout-Senstrienkova E et al. Transfusion 2012;52:

13 Drug treatment options Iron chelators deferoxamine and deferasirox Not first line treatment: side effects, reimbursement issues Proton Pump Inhibitors?

14 Treatment option PPI? 2007: Hutchinson et al. 1 Observational study in 15 C282Y patients Conclusion: significant reduction in number of phlebotomies 1 Hutchinson et al. Gut 2007;56:

15 PPI (2) 2016: van Aerts et al. 1 Retrospective study in 57 C282Y homozygous patients Conclusion: Significant decrease in phlebotomies and SF levels below 100 µg/l with long-term PPI treatment Drawback: Retrospective studies NEED FOR RCT 1 van Aerts RMM, van Deursen CThBM, Koek GH. Clin Gastroenterol Hepatol 2016 Jan;14:147-52

16 Proton pump inhibitors decrease phlebotomy need in HFE related haemochromatosis A double -blind randomized controlled trial He-PPI trial Annick Vanclooster 1, Cees van Deursen 2, Reggy Jaspers 2,3,4, David Cassiman 1, Ger Koek 4 1 University Hospital Leuven. Belgium; 2 Zuyderland Medical Center Heerlen. the Netherlands; 3 Laurentius Hospital Roermond (present), the Netherlands; 4 Maastricht UMC+. the Netherlands

17 PPI RCT: HE-PPI trial Start September 2013 HH patients intervention group (Pantomed 40mg) control group (Placebo) Inclusion C282Y/C282Y, maintenance therapy at least 12 months, 3 phlebotomies per year Ferritin level at start: µg/l Age: years, weight > 50kg

18 Results 31 patients included: 22 men, 8 women Placebo (n=15) PPI (n=15) P-value Age (years as mean with SD) Male Female Age at diagnosis (± 10.5) (± 10.60) (± 12.17) (± 11.04) (± 6.15) (± 7.20) (± 3.70) (± 8.86) Sex Male Female 12 (80%) 3 (20%) 10 (67%) 5 (33%) BMI Male Female (± 3.26) (± 3.51) (± 4.14) (± 6.20)

19 Results HE-PPI trial Placebo (n=15) PPI (n=15) P-value Ferritin level (U/L) 0 months (baseline) 6 months 12 months (end of study) (± 10.02) (± 19.25) (± 37.06) (± 27.55) (± 24.54) (± 46.18) Phlebotomies Year before study During study time 4.87 (± 1.60) 2.60 (± 1.55) 5.33 (± 1.63) 1.27 (± 1.03)

20 Summary and conclusion PPIs significantly decrease the phlebotomy need in p.c282y homozygous patients No serious side effects à PPI should be considered as add-on to standard phlebotomy therapy

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22 Behandeling/opvolging van HH? 3 EB-guidelines AASLD, EASL, Dutch ê 41 recommendations ê Scoring by 15 experts ê Consensus meeting ê 15 key interventions identified

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24 Conclusies Veel bloed belandt in de vuilbak Guidelines voor behandeling en opvolging? à Nood aan consensus Langetermijns resultaten van behandeling van HH? PPI behandeling als goedkope aanvulling