The hepatic involvement in severe Alpha1-antitrypsin deficiency and the circulating polymers

Le résumé fourni par la source

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that primarily affects the lungs due to the reduction of protein levels. The prevalent Z-AAT mutant and many rare pathogenic AAT variants predispose to liver disease due to their accumulation as polymeric chains in hepatocytes. The severity of liver involvement can vary widely among affected individuals. Quantification of circulating polymers (CP) of AAT may be a useful tool in the diagnostic flowchart. Objectives: The aim of our prospective study is to define a clinical work for diagnosis and follow-up of liver profile in patients with severe AATD, and identify the most suitable biochemical or echographic parameters for the management of this rare pathological involvement Methods: We enrolled 76 patients with severe AATD who performed a comprehensive biochemical panel (full metabolic and liver function tests, screening for viral hepatitis, autoimmunity, CBC, screening for overload diseases), CP quantification, hepatic ultrasound, and fibroscan at the time of diagnosis Results: The degree of liver fibrosis was evaluated by hepatic elastosonography and an average stiffness value of 5.43 (SD ±2.11) was associated with a CAP (Controlled Attenuation Parameter) score of 217 (SD ±48). The patients enrolled include different genotypes related to severe deficiency. CP concentrations correlate with genotypes, but a moderate grade of variability is accountable among patients with the same genotype. CP correlate with specific biochemical and echographic parameters, and may be related to the severity of the associated liver diseases Conclusions: These findings highlight the importance of CP quantification in a clinical laboratory.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.