Alpha-1-antitrypsin deficiency (PiZ): Clinical studies with special regard to hepatic and vasculitic disorders

Homozygous alpha-1-antitrypsin (AAT)deficiency (PiZZ) is known to predispose to emphysema and chronic liver disease (CLD). The overall aim of the studies upon which this thesis is based was to investigate extra-pulmonary disease manifestations of AAT deficiency with special reference to hepatic and vasculitic disorders. Both men and women with homozygous AAT deficiency were shown to be at increased risk of cirrhosis (OR=8.3, 42%) and hepatocellular carcinoma (HCC) (OR=5.0, 16%). The risk of HCC was more manifest in men. The risk of cirrhosis or HCC was unrelated to the presence of such environmental factors as alcohol consumption or chronic hepatitis B or C infection. No increased prevalence of viral hepatitis could be found in heterozygous AAT-deficients (PiZ) with CLD, but 63% (5/8) of heterozygotes with hepatitis C infection had severe liver dysfunction. In contrast, a high prevalence of HCV infection was found in patients with low plasma alpha-1-antichymotrypsin (ACT) levels. Among patients with genetic hemochromatosis, 4.5% were found to be homozygous for the PiZ gene, a proportion more than 80-fold greater than that expected in the general population (1/1700) (p