Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers
| Autor: | Mattias Mandorfer, Nadine T. Gaisa, Christian Trautwein, Jef Verbeek, Helmut Denk, Daniel Neureiter, Elmar Aigner, Julia Kümpers, Heinz Zoller, Barbara Burbaum, LS Moeller, Heike Bantel, Olivier Govaere, Federica Benini, Joanna Chorostowska-Wynimko, Aleksander Krag, Frank Lammert, Jacob George, Katharina Wöran, Thomas Reiberger, Georg Lurje, Marla Gutberlet, Felix Stickel, Lisa Bewersdorf, Michael Trauner, Mohammed Eslam, V Woditsch, Sabina Janciauskiene, Tania Roskams, V Pereira, Johannes Haybaeck, J. Voss, Karim Hamesch, C Lindhauer, Annika Gross, Andreas Geier, Mònica Pons, Malin Fromme, Alexander Teumer, Quentin M. Anstee, Joan Genescà, Matthias C. Reichert, Biaohuan Zhou, Pawel Kuca, Marcin Krawczyk, Carolin V. Schneider, Pavel Strnad, Timm Dirrichs, Christian Datz, Joana Carvão, Robert Bals, Frederik Nevens, Benedikt Schäfer |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Adult
Counseling Liver Cirrhosis Male 0301 basic medicine Heterozygote medicine.medical_specialty Cirrhosis ALT Gastroenterology 03 medical and health sciences Liver disease 0302 clinical medicine Liver Function Tests alpha 1-Antitrypsin Deficiency Internal medicine Genotype medicine Humans Longitudinal Studies Prospective Studies Risk factor Aged Alpha 1-antitrypsin deficiency Hepatology business.industry Homozygote Odds ratio Middle Aged medicine.disease United Kingdom GGT Cross-Sectional Studies Phenotype Fibroscan 030104 developmental biology Liver alpha 1-Antitrypsin Cohort Elasticity Imaging Techniques Female SERPINA1 030211 gastroenterology & hepatology Transient elastography business |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Schneider, C V, Hamesch, K, Gross, A, Mandorfer, M, Moeller, L S, Pereira, V, Pons, M, Kuca, P, Reichert, M C, Benini, F, Burbaum, B, Voss, J, Gutberlet, M, Woditsch, V, Lindhauer, C, Fromme, M, Kümpers, J, Bewersdorf, L, Schäfer, B, Eslam, M, Bals, R, Janciauskiene, S, Carvão, J, Neureiter, D, Zhou, B, Wöran, K, Bantel, H, Geier, A, Dirrichs, T, Stickel, F, Teumer, A, Verbeek, J, Nevens, F, Govaere, O, Krawczyk, M, Roskams, T, Haybaeck, J, Lurje, G, Chorostowska-Wynimko, J, Genesca, J, Reiberger, T, Zoller, H, Lammert, F, Krag, A, George, J, Anstee, Q M, Trauner, M, Datz, C, Gaisa, N T, Denk, H & European Alpha-1 Liver Study Group 2020, ' Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers ', Gastroenterology, vol. 159, no. 2, pp. 534-548.e11 . https://doi.org/10.1053/j.gastro.2020.04.058 |
| DOI: | 10.22028/d291-36790 |
| Popis: | BACKGROUND & AIMS: Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease. METHODS: We analyzed data from the European Alpha-1 Liver Cohort, from 419 adults with the Pi∗MZ genotype, 309 adults with the Pi∗ZZ genotype, and 284 individuals without the variant (noncarriers). All underwent a comprehensive evaluation; liver stiffness measurements (LSMs) were made by transient elastography. Liver biopsies were analyzed to define histologic and biochemical features associated with the Pi∗Z variant. Levels of serum transaminases were retrieved from 444,642 participants, available in the United Kingdom biobank. RESULTS: In the UK biobank database, levels of serum transaminases were increased in subjects with the Pi∗MZ genotype compared with noncarriers. In the Alpha-1 Liver Cohort, adults with Pi∗MZ had lower levels of gamma-glutamyl transferase in serum and lower LSMs than adults with the Pi∗ZZ variant, but these were higher than in noncarriers. Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0-11.8). Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype. AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages. Subjects with the Pi∗MZ genotype did not have increased hepatic levels of AAT, whereas levels of insoluble AAT varied among individuals. CONCLUSIONS: Adults with the Pi∗MZ genotype have lower levels of serum transaminases, fewer AAT inclusions in liver, and lower liver stiffness than adults with the Pi∗ZZ genotype, but higher than adults without the Pi∗Z variant. These findings should help determine risk of subjects with the Pi∗MZ genotype and aid in counseling. ispartof: GASTROENTEROLOGY vol:159 issue:2 pages:534-+ ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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