Chronic ‘Cryptogenic’ Liver Disease and Malignant Hepatoma in Intermediate Alpha_rAntitrypsin Deficiency Identified by a Pi Z-Specific Monoclonal Antibody

Abstract

Using a monoclonal antibody against the Pi Z genetic variant of alpha₁-antitrypsin in an enzyme-linked immunosorbent assay, we have screened plasma samples from 857 consecutive patients with liver disease for the presence of Pi Z alpha₁-antitrypsin. Intermediate alpha₁-antitrypsin deficiency (Pi MZ and SZ) was found in 64 cases, or 7.6%, compared with an expected 4.8% (p < 0.001). The plasma alpha₁-antitrypsin level was subnormal in only 50% of them. Forty-three of the 64 heterozygotes were men, compared with 494 of 857 (58%) in the total study population (p < 0.001). At least 14 heterozygotes had cryptogenic liver disease, compared with 3 of 128 sex-and age-matched controls from the same study population (p < 0.001). Malignant hepatoma occurred in 6 heterozygotes compared with 1 control (p < 0.01), and in 13 of all 793 non-Pi Z patients (p < 0.001).

Key Words:

• Intermediate alpha₁-antitrypsin deficiency
• liver disease
• malignant hepatoma