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Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype)
M. Fromme, A. Payancé, M. Mandorfer, KH. Thorhauge, M. Pons, M. Miravitlles, J. Stolk, B. van Hoek, G. Stirnimann, S. Frankova, J. Sperl, AE. Kremer, B. Burbaum, C. Schrader, A. Kadioglu, M. Walkenhaus, CV. Schneider, F. Klebingat, L. Balcar, NN....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, multicentrická studie
Perzistentní odkaz
https://www.medvik.cz/link/bmc25010118
- MeSH
- alfa-1-antitrypsin * genetika krev MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- deficit alfa1-antitrypsinu * genetika diagnóza komplikace MeSH
- dospělí MeSH
- elastografie MeSH
- genotyp MeSH
- homozygot MeSH
- jaterní cirhóza * genetika diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- mutace MeSH
- plíce patofyziologie patologie diagnostické zobrazování MeSH
- plicní nemoci genetika etiologie diagnóza MeSH
- progrese nemoci * MeSH
- rizikové faktory MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.
1st Department of Medicine Paracelsus Medical University Salzburg Salzburg Austria
AP HP service d'hépatologie Hôpital Beaujon AP HP Clichy France DMU Digest Clichy France
Department of Gastroenterology and Hepatology Odense University Hospital Odense C Denmark
Department of Internal Medicine 1 Medical University Innsbruck Innsbruck Austria
Department of Pulmonology Leiden University Medical Center Leiden The Netherlands
Division of Gastroenterology Hepatology and Nutrition University of Florida Gainesville Florida
Division of Hepatology Department of Medicine Leipzig University Medical Center Leipzig Germany
Institute of Applied Health Research University of Birmingham Birmingham United Kingdom
Institute of Liver Studies King's College Hospital NHS Foundation Trust London United Kingdom
Citace poskytuje Crossref.org
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- $a Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype) / $c M. Fromme, A. Payancé, M. Mandorfer, KH. Thorhauge, M. Pons, M. Miravitlles, J. Stolk, B. van Hoek, G. Stirnimann, S. Frankova, J. Sperl, AE. Kremer, B. Burbaum, C. Schrader, A. Kadioglu, M. Walkenhaus, CV. Schneider, F. Klebingat, L. Balcar, NN. Kappe, B. Schaefer, J. Chorostowska-Wynimko, E. Aigner, S. Gensluckner, P. Striedl, P. Roger, J. Ryan, S. Roche, M. Vögelin, A. Ala, H. Bantel, J. Verbeek, Z. Mariño, M. Praktiknjo, TJG. Gevers, PA. Reuken, T. Berg, J. George, M. Demir, T. Bruns, C. Trautwein, H. Zoller, M. Trauner, J. Genesca, WJ. Griffiths, V. Clark, A. Krag, AM. Turner, NG. McElvaney, P. Strnad
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- $a BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.
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