Alpha 1-antitrypsin deficiency and related liver disease

Alpha1-antitrypsin (alpha1 AT) deficiency is a relatively common genetic cause of liver disease among Caucasians. It is an autosomal recessive disorder characterized by reduced serum levels of alpha1 AT, a 52-kD glycoprotein that functions as an antiprotease. The deficiency state is caused by mutations in the alpha1 AT gene on chromosome 14. Alpha1 AT shows considerable genetic variability, having more than 75 genetic variants (Pi types). The PiZ allele is the most common deficiency variant. PiZZ homozygotes have 15-20% of the normal plasma levels of alpha1 AT. The deficiency is due to lack of secretion of Z alpha1 AT from the hepatocyte, where inclusions are formed in the endoplasmic reticulum. Homozygous alpha1 AT deficiency (PiZZ) is known to predispose to emphysema and chronic liver disease. This review outlines the clinical manifestations and treatment of alpha1 AT deficiency associated liver disease, focusing on recent advances in the pathogenic mechanism of liver disease in this genetic disorder.