Alpha1-antitrypsin deficiency is an inherited metabolic disorder in which mutations in the coding sequence of the protease inhibitor, alpha1-antitrypsin, prevent its export from the hepatocyte. Abnormal accumulat ion of alpha1-antitrypsin in hepatocytes results in hepatic inflammation. Patients with the PIZZ phenotype develop clinically significant liver disease which manifests initially as hepatitis followed later by cirrhosis. The mechanisms of liver and lung disease are distinct and unique. Lung disease occurs as a result of deficiency in the concentration of AAT, allowing uninhibited proteolytic damage to the connective tissue of the lung. Diagnosis of alpha1-antitrypsin deficiency can be established by measurement of serum alpha1-antitrypsin concentration and by genotyping.
This article reviews liver disease associated with alpha1-antitrypsin deficiency and analyses a case history.