Vanderbilt Clinical Trials

Participants who meet all the following criteria will be included in the study. Cohorts 1 and 2: 1. Willing to provide written informed consent to participate in the study. 2. >=18 years of age at enrollment in this study. 3. Participants with documented diagnosis of AATD, meeting the following criteria: 1. Cohort 1 (AATD-Pi*ZZ genotype/phenotype). • Pi*ZZ genotype as documented from rapid genetic assay, sequencing, or polymerase chain reaction (PCR), or Pi*ZZ phenotype as documented from iso-electric focusing (IEF) electrophoresis. 2. Cohort 2 (AATD-Pi*SZ genotype/phenotype with liver disease manifestation). - Pi*SZ genotype as documented from rapid genetic assay, sequencing, or PCR, or Pi*SZ phenotype as documented from IEF electrophoresis, and - Moderate-advanced or severe liver disease manifestation as defined by either liver biopsy or surrogate laboratory or imaging measures.

Participants who meet any following criteria will be excluded from the study. 1. Documented AATD genotype/phenotype other than Pi*ZZ or Pi*SZ. 2. History of liver transplant. 3. 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). 4. Participants with prior participation in an interventional clinical trial evaluating liver or lung disease, or who have received an investigational AATD-directed therapy under a compassionate use program, will be excluded if they do not present one of the following: - A minimum washout period of 6 months has elapsed since the last dose of the investigational product. - A history of having received placebo in prior interventional trials (to be evaluated on a case-by-case basis).