Performance of enhanced liver fibrosis test and indirect serum fibrosis markers for exclusion of advanced liver fibrosis in alpha-1 antitrypsin deficiency

Introduction: Alpha-1 antitrypsin deficiency (AATD) (Pi*ZZ) can cause advanced liver fibrosis and cirrhosis in a subset of patients. Transient elastography (TE) to determine degree of fibrosis has been validated in AATD, but is sometimes unavailable. Serum markers of liver fibrosis have not been tested extensively in AATD. Aim was to determine performance of serum markers to exclude significant or advanced fibrosis in Pi*ZZ patients. Methods: In two cohorts of total 362 Pi*ZZ patients with sera and TE from Leiden and Aachen 2015-2023 enhanced liver fibrosis test (ELF), Aspartate aminotransferase to Platelet Ratio Index (APRI), and fibrosis-4 index (FIB-4) were determined retrospectively, and performance for the evaluation of fibrosis status was assessed using TE as gold standard, calculating area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) for excluding significant or advanced fibrosis. Results: AUROC of APRI was highest for significant and advanced fibrosis in both cohorts (Leiden: 0.854 (95 % CI 0.749-0.958), Aachen: 0.684 (95 % CI 0.605-0.763)), followed by FIB-4. ELF had the lowest AUROC for significant fibrosis. For advanced fibrosis AUROC for ELF was slightly higher than for FIB-4. APRI <0.41 demonstrated the best overall diagnostic performance in excluding advanced fibrosis with NPV of 97 %. The limited number of liver-related clinical endpoints within 4 years were predicted by APRI and FIB-4. Conclusion: In Pi*ZZ AATD patients APRI below 0.41 or FIB-4 below 1.79 excludes advanced fibrosis/cirrhosis if TE in unavailable, ELF had no additional value. TE remains the preferred method for staging fibrosis in AATD