Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612693
Poster Visit Session II Clinical Hepatology – Friday, January 26, 2018, 2:35pm – 3:20pm, Room 120
Georg Thieme Verlag KG Stuttgart · New York

Liver Fibrosis and Metabolic Alterations in Adults with Homozygous Alpha1-antitrypsin Deficiency (PiZZ Genotype)

K Hamesch
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
2   Coordinating center for alpha1-antitrypsin deficiency-related liver disease of the European Reference Network (ERN) “Rare Liver” and the European Association for the Study of the Liver (EASL) registry group “Alpha1-Liver”, Aachen
,
C Heimes
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
,
M Mandorfer
3   Medical University Vienna, Clinic for Gastroenterology und Hepatology, Vienna
,
L Moeller
4   Odense University Hospital, Department of Gastroenterology and Hepatology, Odense
,
V Pereira
5   Centro Hospitalar do Funchal, Cirurgia Geral, Funchal, Madeira
,
M Pons
6   Barcelona Hospital, Departmamento de Medicina, Barcelona
,
M Reichert
7   Saarland University Medical Center, Department of Internal Medicine II, Homburg
,
V Woditsch
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
,
J Voß
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
,
T Bretag
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
,
I Spivak
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
,
A Arslanow
7   Saarland University Medical Center, Department of Internal Medicine II, Homburg
,
M Krawczyk
6   Barcelona Hospital, Departmamento de Medicina, Barcelona
,
M Wetzel
8   Charité Berlin, Center for Internal Medicine, Berlin
,
B Siegmund
3   Medical University Vienna, Clinic for Gastroenterology und Hepatology, Vienna
,
E Aigner
3   Medical University Vienna, Clinic for Gastroenterology und Hepatology, Vienna
9   Salzburg University Hospital, Department of Internal Medicine, Salzburg
,
B Schaefer
9   Salzburg University Hospital, Department of Internal Medicine, Salzburg
,
H Zoller
9   Salzburg University Hospital, Department of Internal Medicine, Salzburg
,
T Reiberger
3   Medical University Vienna, Clinic for Gastroenterology und Hepatology, Vienna
,
E Yagmur
10   Medical Care Centre, Dr Stein and Colleagues, Moenchengladbach
,
W Gleiber
11   Department 1, University Hospital Frankfurt, Frankfurt
,
R Bals
12   Saarland University Medical Center, Department of Internal Medicine V, Homburg
,
A Koczulla
13   University Medical Center Gießen and Marburg Philipps-University, Department of Medicine, Pulmonary and Critical Care Medicine, Marburg
,
M Miravittles
14   University Hospital Vall d'Hebron, Pneumology Department, Barcelona
,
S Janciauskiene
15   Medical University Hannover, Clinic for Pneumology, Hannover
,
D Bzdok
16   University RWTH Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen
,
J Genesca
14   University Hospital Vall d'Hebron, Pneumology Department, Barcelona
,
F Lammert
12   Saarland University Medical Center, Department of Internal Medicine V, Homburg
,
M Trauner
3   Medical University Vienna, Clinic for Gastroenterology und Hepatology, Vienna
,
A Krag
4   Odense University Hospital, Department of Gastroenterology and Hepatology, Odense
,
C Trautwein
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
2   Coordinating center for alpha1-antitrypsin deficiency-related liver disease of the European Reference Network (ERN) “Rare Liver” and the European Association for the Study of the Liver (EASL) registry group “Alpha1-Liver”, Aachen
,
P Strnad
1   University Hospital RWTH Aachen, Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, Aachen
2   Coordinating center for alpha1-antitrypsin deficiency-related liver disease of the European Reference Network (ERN) “Rare Liver” and the European Association for the Study of the Liver (EASL) registry group “Alpha1-Liver”, Aachen
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

Also available at
 
 

    Background:

    Alpha1-antitrypsin deficiency (AATD) predisposes to lung and liver disease. It is among the most common genetic disorders but the liver phenotype in adults is still poorly characterized. Therefore, we assessed the liver disease burden in a European cohort of AATD adults with the classical homozygous Z mutation termed “PiZZ”.

    Methods:

    In cooperation with patient organizations and specialized pneumologists, we recruited 411 adults with the PiZZ genotype from Germany, Austria, Denmark, Portugal, Spain, Belgium and the Netherlands (mean age 54 years, 45% female, mean BMI 24.8 kg/m2) as well as 243 non-carriers (NC) without AAT mutation. Participants underwent a thorough clinical and laboratory workup to exclude hepatic comorbidity and to assess pulmonary symptoms. FibroScan determined liver fibrosis via liver stiffness measurement (LSM) and liver steatosis via controlled attenuation parameter (CAP). Data were adjusted for age, sex, BMI, diabetes mellitus and alcohol consumption where appropriate.

    Results:

    Despite ongoing lung care, ˜80% of PiZZ adults did not receive regular liver check-ups. In PiZZ subjects, serum liver enzymes were only rarely elevated above the sex-specific upper limit of normal (ALT 19%, AST 13% and GGT 24%), but their mean levels were higher than in NC (all: p<.0001). Mean LSM was higher in PiZZ carriers than NC (6.7 ± 5.8 vs. 4.6 ± 1.7 kPa, p<.0001). LSM ≥7.1 kPa, indicating significant liver fibrosis, was detected in 24% of PiZZ patients and in 7% of NC (OR = 5.7 [3.0 – 10.9]). Among PiZZ subjects, the following parameters conferred higher odds ratios (OR) for LSM ≥7.1 kPa: Elevated AST (OR = 5.7 [2.8 – 11.9]) or GGT (OR = 4.0 [2.27 – 7.1]) as well as BMI ≥30 kg/m2 (OR = 3.4 [1.7 – 6.9]). CAp ≥280 dB/m, indicating severe liver steatosis, was observed in 39% of PiZZ patients and in 31% of NC (OR = 2.1 [1.4 – 3.3]). In line with human data, PiZ-overexpressing mice displayed mild steatosis. As likely contributing mechanism, PiZZ patients showed lower serum triglyceride, VLDL and LDL cholesterol levels than NC (all p<.01). Importantly, the presence of liver fibrosis or steatosis was not associated with the severity of lung disease (COPD assessment test or need for oxygen therapy), intravenous AAT substitution or age. Finally, a score consisting of gender, BMI, GGT and platelets predicted the presence of significant liver fibrosis with a 85% accuracy.

    Conclusion:

    Using a large, multi-national cohort, we uncovered metabolic alterations and defined the liver phenotype of PiZZ individuals. Together with the identified predictors, our findings depict a novel, non-invasive approach to assess liver affection in PiZZ adults.


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