Association of circulating Z‐polymer with adverse clinical outcomes and liver fibrosis in adults with alpha‐1 antitrypsin deficiency

• DOI: 10.1002/ueg2.12629
• Publication Date: 2024-07-18T15:58:57Z
• Authors: Malin Fromme; Laura Rademacher; Samira Amzou; Christi D. Cook; Isabel Zacharias; Lanju Zhang; John E. Ripollone; Pavel Strnad
• Keywords: Transient elastography; Alpha 1-antitrypsin deficiency; Liver disease

Abstract Background Circulating polymerized mutant Z‐alpha‐1 antitrypsin (Z‐polymer) constitutes a characteristic feature in alpha‐1 deficiency (AATD), but there is limited knowledge about its association with adverse clinical outcomes and liver fibrosis. We explored this using data from large cohort of adults AATD. Methods A total 836 (431 PiZZ, 405 PiMZ) AATD 312 controls (PiMM) the European Alpha‐1 Liver Cohort (2015–2020) were included. Time‐to‐event analyses conducted for PiZZ genotype followed (earliest occurrence liver‐related hospitalization, transplant or all‐cause mortality). Cox proportional hazard models used to describe between binary circulating Z‐polymer levels outcomes. Correlations baseline fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) evaluated. The stratified augmentation therapy status. Results Of 324 longitudinal follow‐up data, 28 reported Higher associated an increased risk both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) age‐adjusted (1.96 [0.78, 4.94]) analyses. In genotype, weakly positively correlated LSM (Spearman's rho CI]: 0.21 [0.11, 0.31]). Similar results observed after stratification Conclusions higher shorter time outcome, LSM. may be prognostic biomarker clinically relevant disease