Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Determination of Pi phenotypes using iso-electric focusing.

Alpha-1-antitrypsin (AAT) deficiency resulting from the homozygous protease inhibitor (Pi) ZZ and the heterozygous Pi Z states has been reported to be aetiologically associated with hepatocellular carcinoma (HCC). We studied the phenotype distribution of AAT variants (Pi) by iso-electric focusing on polyacrylamide gel and measured serum AAT concentrations by rocket immuno-electrophoresis in 80 unselected southern African Black patients with HCC and 103 age-, sex- and tribally matched control subjects. Aberrant (non-MM) phenotypes were present in 7 HCC patients (8,7%) and 13 controls (12,6%), an insignificant difference. None of the patients or controls had the Pi ZZ phenotype, while 4 HCC patients (5,0%) and 2 controls (1,9%) (P greater than 0,05) were found to be heterozygous carriers of the Z gene. No HCC patient had a subnormal serum AAT value, and the values in the patients were not lower than those in the controls. We conclude that AAT deficiency does not play an aetiological role in HCC in southern African Blacks. The 4 patients with the heterozygous Z phenotype did not have fibrolamellar carcinomas.