Clinical Utility of Non-Invasive Tests for Liver Fibrosis in People Living With Alpha-1 Antitrypsin Deficiency

Severe alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition characterised by low systemic levels of alpha-1 antitrypsin due to its retention in the liver. Consequently, it predisposes individuals to the development of chronic obstructive pulmonary disease and liver cirrhosis. Much progress has been made to non-invasively monitor liver fibrosis and cirrhosis in individuals with other liver diseases, but it remains unclear how to assess liver disease in people with AATD. This narrative review examined the available evidence on non-invasive tests (NITs) to stage liver fibrosis and predict incident major adverse liver outcomes in people with AATD. Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE), blood-based NITs, and serum liver enzymes are generally normal or mildly elevated in individuals with AATD. Further, VCTE-LSM and blood-based NITs, including the AST to platelet ratio index and fibrosis-4 score, have diagnostic utility for predicting F2 and F3 fibrosis and hold excellent (AUROC ≥ 0.90) prognostic value for incident major adverse liver outcomes. Gamma-glutamyl transferase also exhibits diagnostic and prognostic utility but is subject to multiple non-AATD-related fluctuations. A potential strategy to non-invasively assess liver disease stage and estimate the risk of major adverse liver outcomes in people with AATD could consist of a combination of VCTE-LSM with blood-based biomarker panels. Future studies should explore if liver stiffness naturally fluctuates over time in people with AATD, assess the ideal frequency of follow-up, and evaluate if NITs can guide the treatment of AATD-related liver disease.