HEPATOCYTIC GLOBULES IN END-STAGE HEPATIC-DISEASE - RELATIONSHIP TO ALPHA(1)-ANTITRYPSIN PHENOTYPE

Hepatic explant specimens from 171 patients with cirrhosis were examin ed to determine the incidence of periodic acid-Schiff (PAS)-positive d iastase-resistant globules (PDRGs) in end-stage hepatic disease and wh ether the globules bear a specific relationship to the alpha(1)-antitr ypsin (A(1)AT) phenotype or to causes of hepatic disease other than A( 1)AT deficiency. PAS-positive diastase-resistant globules were detecte d in 17 (10%) of the hepatic explant specimens, and the globules in al l of these cases were strongly immunoreactive for A(1)AT. In the 17 pa tients with FDRGs, the cirrhosis was attributed preoperatively to A(1) AT deficiency (3 patients), ethanol abuse, viral hepatitis, or both (1 0 patients), cryptogenic cirrhosis (3 patients), and autoimmune hepati tis (1 patient). The A(1)AT isoelectric phenotypes classified accordin g to the protease inhibitor (Pi) nomenclature for 16 of these patients were as follows: Pi ZZ (3 patients), Pi SS (1 patient), Pi MZ ( pati ents), and Pi MM (4 patients). Because PDRGs were seen in a variety of A(1)AT phenotypes, serum electrophoretic analysis, not histologic exa mination, is required for the correct diagnosis of an A(1)AT abnormali ty. Furthermore, although PDRGs were seen in a variety of hepatic dise ases, the majority of patients with globules had an undetected A(1)AT abnormality. Accordingly, on identification of hepatocytic PDRGs, the clinician should be alerted to the possibility of an unsuspected A(1)A T abnormality even in the presence of other causes of hepatic disease.