Alpha-1-antitrypsin bodies in the liver.

Abstract

SUMMARY The cytoplasmic bodies in hepatocytes thought to indicate possession of the Z allele for a1-antitrypsin deficiency were found at necropsy in 10 of 64 adults with cirrhosis, four of nine with hepatic fibrosis, and four of 15 with hepatocellular carcinoma. They were also found in six of 76 adults with severe panacinar emphysema, and in four of a control series of 110 adults with neither emphysema nor liver disease. The association of the bodies with each of the three liver diseases was statistically significant, but the association of the bodies with emphysema was not. It is considered probable that heterozygous (PiMZ) a,-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma. 28 June 1976 records were examined for cases of hepatic fibrosis, hepatoma, and cirrhosis other than that due to large duct obstruction: 64 cirrhotic livers (11 with hepatocellular carcinoma), nine fibrotic livers (1 with hepatocellular carcinoma), and three livers with hepatocellular carcinoma but neither cirrhosis nor fibrosis were found; blocks of non-neoplastic liver were available from all cases (76), and blocks of hepatocellular carcinoma from the 15 cases with hepatocellular carcinoma. The control series consisted of blocks of liver from 110 consecutive adult necropsies in which there was neither clinical nor pathological evidence of liver disease or emphysema.All the liver blocks were formalin-fixed and paraffin-embedded. Sections were cut at 4 ,um: one section from each case was stained with haematoxylin and eosin, one for reticulin, and one with periodic acid Schiff after diastase. The diagnosis on the liver was checked and confirmed in each case. The characteristic acx-antitrypsin bodies were not stained in the haematoxylin and eosin preparation but were seen as rounded, sharply-defined, solid bodies staining strongly with periodic acid Schiff after diastase, in the cytoplasm of hepatocytes, predominantly in the periportal cells. Bodies up to at least 3 ,um diameter were found in each positive case, and frequently bodies up to 15,um diameter were present. In addition, sections were cut at 4 ,um from the liver blocks of all cases with cirrhosis, hepatic fibrosis or hepatocellular carcinoma, of all cases showing cxlantitrypsin bodies on periodic acid Schiff staining, and of 27 cases of emphysema randomly selected from those without cti-antitrypsin bodies oa periodic acid Schiff staining: these were mounted on albumin-132

Alpha1-antitrypsin bodies, PiZ phenotype, and peptic ulcer.

“…The results are shown in the Table, which also gives the results in a previous control series (Blenkinsopp and Haffenden, 1977). Chi-square tests revealed no significant difference between any test group and the controls, and thus no evidence of an association between al-antitrypsin deficiency and peptic ulceration.…”

“…Probably all persons with a PiZ allele have typical periodic acid-Schiff positive, diastase resistant, rounded bodies in the cytoplasm of their hepatocytes (Blenkinsopp and Haffenden, 1977), and these bodies rarely occur in persons with normal PiMM phenotype (Bradfield and Blenkinsopp, 1977). Andre et al (1974) reported that 10.5% of 114 patients with chronic duodenal ulcer, and 9-6 % of 83 with chronic gastric ulcer, had levels of al-antitrypsin in the heterozygous (PiMZ) range, compared with 3-3% of 118 controls.…”

Demonstration of alpha1-antitrypsin in paraffin sections of hepatoma and cirrhosis

“…Immunocytochemicat and histological studies using intracytoplasmic liver AAT globules as markers have suggested that there is an increased incidence of the Z allele in cases of HCC (Blenkinsopp and Haffenden 1977; or cirrhosis (Blenkinsopp and Haffenden 1977;Eriksson et al 1975), although phenotypic studies have shown no statistically significant increase of Z allele in cases of HCC and cirrhosis (Peters 1976;Theodoropoulos et al 1976). More recently, Kelly et al (1979), in a series of 42 cases of HCC and 98 controls, described typical AAT globules stained most strongly at the globule periphery in the non-neoplastic liver tissue of two (5%) of HCC.…”

Molecular pathogenesis of liver disease in ?1-antitrypsin deficiency

“…In the Austrian study only 3 of the 9 homozy-seen in other hepatic cell types. [109][110][111][112][113] The liver biopsy may also be characterized by a variable degree of cholestasis, hegotes had clinically significant liver injury and only one had evidence of viral infection. 92 In a 14-year experience at St. patocellular necrosis, inflammatory cell infiltrate, bile duct epithelial cell destruction, and periportal fibrosis or cirrhosis.…”