With several promising therapies for AATD-related liver disease now in development including RNA interference–based silencing of mutant SERPINA1, gene replacement strategies, and hepatocyte-directed proteostasis modulators, identifying reliable prognostic factors has become increasingly important to define which patients are most likely to benefit and to optimize clinical trial design (7, 8). The gene discussed is SERPINA1; the disease is alpha 1-antitrypsin deficiency.