Z Gastroenterol 2025; 63(01): e3-e4
DOI: 10.1055/s-0044-1800994
Abstracts │ GASL
Lecture Session III
METABOLISM (INCL. MASLD) 14/02/2025, 05.50pm – 06.35pm, Lecture Hall

Interaktion zwischen metabolischen Faktoren und Genetik am Beispiel Alpha-1-Antitrypsin-Mangel

Christina Schrader
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Malin Fromme
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Audrey Payancé
2   AP-HP, service d'hépatologie, Hôpital Beaujon, DMU Digest, Centre de référence des Maladies Vasculaires du foie, FILFOIE, Clichy, Université Paris Cité, ERN RARE LIVER, Paris, France
,
Mattias Mandorfer
3   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria
,
Katrine H. Thorhauge
4   Department of Gastroenterology and Hepatology, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark
,
Monica Pons
5   Liver Unit, Vall d’Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
,
Marc Miravitlles
6   Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), ERN LUNG, Barcelona, Spain
,
Jan Stolk
7   Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
,
Bart van Hoek
8   Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
,
Guido Stirnimann
9   University Clinic for Visceral Surgery and Medicine, University Hospital Inselspital and University of Bern, Bern, Switzerland
,
Sona Frankova
10   Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, ERN RARE LIVER, Prague, Czech Republic
,
Jan Sperl
10   Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, ERN RARE LIVER, Prague, Czech Republic
,
Andreas E Kremer
11   Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Katharina Remih
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Barbara Burbaum
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Amine Kadioglu
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Michelle Walkenhaus
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Carolin Victoria Schneider
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Fabienne Klebingat
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Lorenz Balcar
3   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria
,
Annelot D. Sark
7   Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
,
Benedikt Schaefer
12   Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
,
Joanna Chorostowska-Wynimko
13   Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
,
Elmar Aigner
14   First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
,
Sophie Gensluckner
14   First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
,
Philipp Striedl
14   First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
,
Pauline Roger
15   AP-HP, service d'hépatologie, Hôpital Beaujon, AP-HP, Clichy, France, DMU Digest, Clichy, France
,
John Ryan
16   Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
,
Suzanne Roche
16   Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
,
Marius Vögelin
11   Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
,
Aftab Ala
17   Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
,
Heike Bantel
18   Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
,
Jef Verbeek
19   Department of Gastroenterology & Hepatology, KU Leuven University Hospitals, ERN RARE LIVER, Leuven, Belgium
,
Zoe Mariño
20   Liver Unit, Hospital Clínic Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona
,
Michael Praktiknjo
21   Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, University Hospital Muenster, Muenster, Germany
,
Tom J.G. Gevers
22   Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands
,
Philipp Reuken
23   Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
,
Thomas Berg
24   Division of Hepatology, Department of Medicine, Leipzig University Medical Center, Leipzig, Germany
,
Jacob George
25   Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
,
Münevver Demir
26   Department of Hepatology and Gastroenterology, Campus Virchow-Hospital and Campus Charité Mitte, Charité – Berlin University Medicine, ERN RARE LIVER, Berlin, Germany
,
Tony Bruns
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Christian Trautwein
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Heinz Zoller
12   Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
,
Michael Trauner
3   Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria
,
Joan Genesca
5   Liver Unit, Vall d’Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
,
William J. Griffiths
27   Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
,
Virginia Clark
28   Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, United States
,
Aleksander Krag
4   Department of Gastroenterology and Hepatology, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark
,
Noel G. McElvaney
16   Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
,
Alice Turner
29   Institute of Applied Health Research, University of Birmingham, Birmingham, UK
,
Pavel Strnad
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, RWTH Aachen University Hospital, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
› Author Affiliations
 
 

    Einleitung und Ziel: Ziel dieser Studie ist es, die Einflüsse von Diabetes und Body-Mass-Index (BMI) auf den Alpha-1-Antitrypsin-Mangel (AATM)-assoziierten Leberphänotyp sowie die Entwicklung hepatischer Endpunkte zu analysieren.

    Methodik: Diese multizentrische Kohorte umfasst 1.890 Individuen mit schwerem AATM (Pi*ZZ), von denen 928 nach mind. 6 Monaten ein Follow-up erhielten. Hepatische Endpunkte wurden definiert als Lebertransplantation, leberbedingte Todesfälle und erste hepatische Dekompensation. Der Vergleich mit Individuen ohne (Pi*MM) sowie mit heterozygotem AATM (Pi*MZ) erfolgte mittels UK Biobank.

    Ergebnis: Bei Baseline waren 67 Pi*ZZ Teilnehmende Diabetiker, 621 übergewichtig (BMI 25.0-29.9 kg/m2) und 305 adipös (BMI≥30 kg/m2). Diabetiker wiesen im Vergleich zu Nicht-Diabetikern signifikant häufiger erhöhte ALT-, AST-, GGT-Werte auf (27-61% vs. 13-24%). Fortgeschrittene Fibrose war unter Diabetikern fünfmal häufiger (OR 4.7-5.4). In den normalgewichtigen Pi*ZZlern waren erhöhte Leberwerte selten (9-20%), häufiger bei übergewichtigen (16-31%; OR 1.9-2.4) und adipösen (23-37%, OR 2.4-3.0). Fortgeschrittene Leberfibrose war fast fünfmal häufiger in adipösen (12%, OR 4.3-4.8) und fast dreimal häufiger in übergewichtigen Individuen (8%, OR 2.4-3.0). Während eines medianen Follow-ups von 4 Jahren erlebten 55 Pi*ZZler einen Leberendpunkt. Diabetiker und adipöse Teilnehmende wiesen ein erhöhtes Risiko für einen Leberendpunkt auf (HR=3.8-6.2, p<0.001). In der Pi*MZ- und Pi*MM-Kohorte waren die ORs für erhöhte Leberwerte, fortgeschrittene Fibrose und Leberendpunkte bei Diabetikern kleiner und bei Übergewicht und Adipositas vergleichbar zur Pi*ZZ-Kohorte.

    Schlussfolgerung: Diabetes und Adipositas sind Genotyp-unabhängig mit erhöhten Lebersurrogatmarkern und einem erhöhten Risiko für eine Dekompensation verbunden, die prozentuale Auswirkung ist unter Pi*ZZ Individuen jedoch am prägnantesten. Diese Daten ermöglichen eine personalisierte Versorgung und Beratung.


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    Publication History

    Article published online:
    20 January 2025

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