Liver disease progression in patients with alpha-1 antitrypsin deficiency and protease inhibitor ZZ genotype with or without lung disease.

ABSTRACT

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha-1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood. AIMS: To characterise patients with AATD Pi*ZZ and liver disease (AATD-LD-Pi*ZZ) with or without lung disease and describe liver disease-related clinical events longitudinally. METHODS: This was an observational cohort study of patients in the Mayo Clinic Healthcare System (January 2000-September 2021). Patients were identified using diagnosis codes and natural language processing. Fibrosis stage (F0-F4) was assessed using a hierarchical approach at baseline (90 days before or after the index date) and follow-up. Clinical events associated with liver disease progression were assessed. RESULTS: AATD-LD-Pi*ZZ patients with lung disease had a longer median time from AATD diagnosis to liver disease diagnosis versus those without lung disease (2.2 vs. 0.2 years, respectively). Compared to those without lung disease, patients with lung disease had a longer time to liver disease-related clinical events (8.5 years and not reached, respectively). AATD-LD-Pi*ZZ patients without lung disease were more likely to undergo liver transplantation compared with those with lung disease. CONCLUSION: In patients with AATD and lung disease, there is a delay in the diagnosis of comorbid liver disease. Our findings suggest that liver disease may progress more rapidly in patients without comorbid lung disease.