The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of AAT, called Z-AAT. Z-AAT builds up in liver cells and also leads to low blood levels of AAT (called Alpha-1 Antitrypsin Deficiency or AATD). Over time, this build up leads to different stages of liver problems, if not treated. This is called natural history of AATD.
The main aim of this study is to learn about liver problems caused by AATD in adults when not treated over 4 to 8 years. Other aims are to learn what can predict the AATD-liver condition starting and getting better or worse, describe how this condition is currently being diagnosed and watched in normal care, and describe how the AATD also affects an adult's lung function.
Data in this study will be collected to include medical history of a participant, including the date AATD was first identified and/or the date on which the first AATD-related liver or lung problems were diagnosed. At study start and then every year until study end, participants will be asked to complete questionnaires (called patient-reported outcomes or PROs).
Willing to provide written informed consent to participate in the study.
>=18 years of age at enrollment in this study.
Cohort 1 (AATD-Pi*ZZ genotype/phenotype).
Cohort 2 (AATD-Pi*SZ genotype/phenotype with liver disease manifestation).
Documented AATD genotype/phenotype other than Pi*ZZ or Pi*SZ.
History of liver transplant.
No results for either biopsies, magnetic resonance elastography (MRE), FibroScan (vibration controlled transient elastography [VCTE]), or Aspartate aminotransferase to platelet ratio index (APRI) in the 24 months prior to the index/enrollment date and has none of these tests ordered during the index period (i.e., index date +90 days).
A minimum washout period of 6 months has elapsed since the last dose of the investigational product.