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.
Participants who have already been diagnosed with AATD of genotype/phenotype Pi\*ZZ, with or without liver disease manifestation (F0-F4dc), or with genotype/phenotype of Pi\*SZ with moderate-advanced or severe liver disease manifestation (F2-F4dc).
Cohort
Prospective
No Intervention
Other interventionThis is an observational study.
Number of Participants With Liver Disease Progression
Liver disease progression will be defined as advancement in greater than or equal to (\>=)1 fibrosis stage: example any progression from fibrosis stage F0/F1 to F2, F1 to F2, F2 to F3 etc. and/or occurrence of any of these composite events: a) advancement in \>=1 fibrosis stage, b) development of a liver disease-related clinical event, c) model for end-stage liver disease (MELD) score increase, d) newly added on liver transplant list, e) receipt of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Time to Liver Disease Progression
Time to liver disease progression is defined as time to advancement in \>=1 fibrosis stage (example F0/F1 to F2, F2 to F3 etc.) and/or time to the earliest of: Advancement in \>=1 fibrosis stage, or development of a liver disease-related clinical event, or MELD score increase or receipt/newly added to transplant list of a liver transplant. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.
Time to Liver Disease Trajectory
Time to liver disease trajectory is defined as time of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Probability of Transition in Liver Disease Trajectory
Probability of liver disease trajectory is defined as probability of transition from F0/F1 to F2, F2 to F3, F3 to F4, F4 to the first decompensating event or liver transplant/listing and first to second decompensating event and all subsequent decompensating events or liver transplant/listing. The fibrosis stages range from F0 to F4, with F0 indicating no fibrosis and F4 indicating cirrhosis.
Percentage of Participants Who Develop Lung Disease
Development of lung disease will be defined as either a forced expiratory volume in 1 second (FEV1) percent (%) predicted of less than (\<) 70% or the diagnosis of at least 1 lung condition (chronic obstructive pulmonary disease \[COPD\], emphysema, bronchiectasis, chronic bronchitis) over the study duration or at specific timepoints.
Proportion of Participants With Lung Disease at Baseline who Experience Lung Disease Progression at 4-8 Years
Lung disease progression is defined as changes in pulmonary function (defined as \>=10% absolute change in FEV1, forced vital capacity \[FVC\], or diffusing capacity of the lungs for carbon monoxide \[DLCO\]) over the study duration or at specific timepoints.
Characterize Diagnostic and Monitoring Patterns for Liver Disease (Invasive and Non-invasive Assessments)
