Diagnosis and Monitoring Pathways Using Non-Invasive Tests in Patients With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease: Results From an Expert Delphi Panel

Virginia C Clark; Mark A Price; Jon Russo; Rohit Loomba; Alice M Turner; Pavel Strnad

doi:10.1002/ueg2.70009

Diagnosis and Monitoring Pathways Using Non-Invasive Tests in Patients With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease: Results From an Expert Delphi Panel

United European Gastroenterol J. 2025 Mar 12. doi: 10.1002/ueg2.70009. Online ahead of print.

Authors

Virginia C Clark¹, Mark A Price², Jon Russo², Rohit Loomba³, Alice M Turner⁴, Pavel Strnad⁵

Affiliations

¹ University of Florida, Gainesville, Florida, USA.
² RTI Health Solutions, Research Triangle Park, North Carolina, USA.
³ University of California San Diego School of Medicine, San Diego, California, USA.
⁴ University of Birmingham, Birmingham, UK.
⁵ University Hospital RWTH Aachen, Aachen, Germany.

PMID: 40072894
DOI: 10.1002/ueg2.70009

Abstract

Background and aims: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Keywords: Delphi; alpha‐1 antitrypsin deficiency; liver fibrosis.

Abstract

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