Alpha1-AntiTrypsin Deficiency : Cirrhosis

Deficiencies in the serum protease inhibitor alpha1-antitrypsin (AAT) result from AAT gene mutations. Heterozygous (PiMZ) and homozygous (PiZZ) individuals have moderate and severe deficiencies, respectively. The mutant Z allele encodes a structural change in the glycoprotein (lysine in place of glutamic acid at position 342), resulting in abnormal folding and retention in the endoplasmic reticulum, leading to accumulation of eosinophilic, PASD+ globules in hepatocytes. The globules are 1-10 microns and the larger ones are seen on H&E (above). This may progress to chronic hepatitis with fibrosis, prominent ductular reaction, or cirrhosis, as shown here.