Diagnosis and Monitoring Pathways Using Non-Invasive Tests in Patients With Alpha-1 Antitrypsin Deficiency-Associated...

The severe alpha-1 antitrypsin deficiency (AATD) genotype Pi*ZZ increases the risk of liver disease (AATD-LD) and lung disease. While non-invasive tests (NITs) are widely used for fibrosis stage and monitoring of all liver diseases, the consensus for use in AATD-LD is limited. A Delphi panel study was conducted to address this need.

Healthcare providers who managed at least two patients with AATD-LD in the past two years participated. Two iterative surveys were developed and administered. The second survey clarified the results from the first and provided deeper feedback. As follow-up, a real-time consensus-building exercise focused on survey topics without consensus. Controlled feedback was anonymous.

A total of 20 AATD experts (hepatology [n = 9], pulmonology [n = 6], transplant hepatology [n = 3], gastroenterology [n = 1], and hepatology and transplant hepatology [n = 1]) completed the study. A strong consensus was achieved around the use and evaluation of NITs for risk stratification and monitoring. All panelists agreed that vibration-controlled transient elastography (VCTE) is the preferred NIT for the initial assessment of AATD-LD owing to its accessibility and reliability. Magnetic resonance elastography and enhanced liver fibrosis tests were also considered valuable. Most (85%) agreed that VCTE < 8 kPa could indicate no or mild fibrosis and VCTE ≥ 8 kPa could indicate clinically significant fibrosis, which may correspond to fibrosis stage ≥ F2 on the METAVIR scale. Most (85%) agreed that VCTE ≥ 13 kPa may indicate cirrhosis.

Utilizing the Delphi technique, this study identified a clinically applicable framework for the diagnosis and monitoring of AATD-LD. A high level of agreement emerged regarding preferred NITs and their usage, risk stratification and monitoring in the context of AATD-LD management. The results provide a foundation for future efforts into NIT validation and the development of clinical guidelines for AATD-LD.