Hamesch K, Mandorfer M, Pereira VM, et al. - Given that severe α1-antitrypsin deficiency (AATD), most common genetic disorders, is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation), researchers evaluated the liver disease burden and characteristics in adults with this form of AATD. Data were collected from 554 adults, in nine European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without previously known liver disease. Higher liver fibrosis burden was linked to the male sex, age older than 50 years, increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase, and low numbers of platelets. The authors discovered proof of liver steatosis and impaired lipid secretion in studies of AATD patients with Pi*ZZ mutation and Pi*Z-overexpressing mice. Factors associated with significant liver fibrosis in patients were identified, which could facilitate hepatologic assessment and counseling of people who carry the Pi*ZZ mutation.