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APRI and FIB-4 blood tests effectively rule out advanced fibrosis in Pi*ZZ alpha-1 antitrypsin deficiency, providing a reliable, non-invasive alternative to liver elastography.
Alpha-1 antitrypsin deficiency (AATD; Pi*ZZ) may silently drive severe liver damage, including advanced fibrosis and cirrhosis, in some people. Although transient elastography (TE) reliably measures fibrosis, it isn’t always available, and blood-based markers remain underexplored. Hence, this cohort-based research aimed to determine how accurately serum-based tests could exclude significant or advanced liver fibrosis in Pi*ZZ patients.
A total of 362 Pi*ZZ patients from Leiden and Aachen (2015–2023) with available sera and TE data were retrospectively analyzed. Serum fibrosis markers—including the enhanced liver fibrosis (ELF) test, aspartate aminotransferase to platelet ratio index (APRI), and fibrosis-4 index (FIB-4)—were estimated. TE served as the reference standard for fibrosis staging, and the diagnostic performance of each serum marker was assessed using the area under the receiver operating characteristic curve (AUROC) and the negative predictive value (NPV) to exclude significant or advanced fibrosis.
The analysis revealed that APRI achieved the highest AUROC for identifying both significant and advanced fibrosis (Leiden: 0.854, 95% CI 0.749–0.958; Aachen: 0.684, 95% CI 0.605–0.763), followed by FIB-4. ELF exhibited the lowest AUROC for significant fibrosis, though its performance for advanced fibrosis slightly surpassed that of FIB-4. An APRI cutoff below 0.41 provided the most reliable diagnostic accuracy for excluding advanced fibrosis, with a NPV of 97%. Additionally, APRI and FIB-4 successfully predicted the limited liver-related clinical events observed over the 4-year follow-up period.
The study group concluded that APRI and FIB-4 serve as reliable non-invasive tools to exclude advanced fibrosis or cirrhosis in Pi*ZZ AATD patients when TE is unavailable, whereas ELF provided no additional benefit. Nonetheless, TE remains the benchmark for accurate fibrosis assessment.
European Journal of Internal Medicine
Performance of enhanced liver fibrosis test and indirect serum fibrosis markers for exclusion of advanced liver fibrosis in alpha-1 antitrypsin deficiency
Naomi N Kappe et al.
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