Increased Frequency of Heterozygous Alpha‐1‐Antitrypsin Deficiency in Liver Explants From Nonalcoholic Steatohepatitis Patients

Cirrhotic explanted livers occasionally have unexpected periodic acid-Schiff-diastase (PASD)-positive globules within the hepatocyte cytoplasm. It is often unclear whether this finding is a nonspecific consequence of cirrhosis or is indicative of an underlying alpha-1-antitrypsin deficiency (A1ATD) contributing to the cirrhosis. In this study, explanted livers were retrospectively evaluated for histopathology (including PASD status with confirmatory alpha-1-antitrypsin [A1AT] immunohistochemistry [IHC]), and chart review provided etiology of liver failure and general clinical parameters. Real-time polymerase chain reaction was used to detect A1AT genotype (SERPINA1 S and Z alleles) by melting curve analysis on liver explant tissue from selected cases. Of 196 explanted livers, 21 (11%) had PASD+ globules, which were significantly enriched in patients with a clinical diagnosis of nonalcoholic steatohepatitis (NASH; 47%) compared with other causes (P