The diagnostic value of α₁‐antitrypsin globules in liver cells as a morphological marker of α₁‐antitrypsin deficiency

Abstract

ABSTRACT— In order to determine the diagnostic value of α1‐antitrypsin (AAT) globules as a morphological marker of AAT‐deficiency of the Pi‐Z type, liver needle biopsies from a prospective series of 600 patients were stained with PAS after pretreatment with diastase and by indirect immunoperoxidase staining for AAT deposits. Serum AAT phenotypes of the patients were determined by means of isoelectric focusing. Thirty‐two biopsies were from patients with the Pi‐Z allele (31 MZ, 1 Z), and 568 biopsies from patients without the Pi‐Z allele. AAT globules larger than 3 μm were found in 16 biopsies of which 15 were from patients with the Pi‐Z allele (diagnostic specificity 0.94), whereas 20 of 26 biopsies with AAT globules larger than 1 μm were from Pi‐Z patients (diagnostic specificity 0.77). Only 47% of the biopsies from patients with the Pi‐Z allele contained AAT globules larger than 3 μm. Thus, although AAT globules larger than 3 μm are highly specific as a morphological marker of the Pi‐Z allele, their rather infrequent occurrence in carriers of the Pi‐Z allele indicates that all investigations concerning the correlation between AAT deficiency of the Pi‐Z type and liver disease should be based on phenotyping of sera from all the patients.

Alpha 1 antitrypsin deficiency in children with chronic liver disease in North India

“…these techniques have issues of low specificity with high false positivity (9) and no confirmed case based on either Isoelectric focusing (IEF) or PCR based assay has ever been reported in India. In view of this background, we attempted to determine prevalence of AAT deficiency among pediatric chronic liver disease patients in North India using diagnostic tests INDIAN PEDIATRICS 1016 VOLUME 47 __ DECEMBER 17, 2010 (IEF and genotyping) that are considered gold standard.…”

Molecular confirmation of alpha 1-antitrypsin deficiency in liver transplant setting: A province-wide experience

“…Moreover, not all patients who are heterozygous for the Z allele demonstrate PASD/A1AT-positive globules, as is demonstrated by their follow-up study in 1984, showing that only 47% of patients with a confirmed (through Isoelectric Focusing) Pi*Z allele demonstrate PASD/A1AT-positive globules (>3 um) on their liver tissue histology. [ 20 ] This suggests that the globules, albeit specific, are not sufficiently sensitive or reliable as a screening tool for heterozygous Z allele.…”

Clinical, Laboratorial and Evolutionary Aspects of Pediatric Patients With Liver Disease Due to Alpha 1-Antitrypsin Deficiency

“…However, Teckman et al (9) (2015) suggest that this may be a weak association, since many patients who are initially cholestatic may have a good evolution, sometimes with spontaneous improvement over time. The PI*ZZ phenotype has also been associated with moderate to severe disease and constitutes the majority of patients with AATD liver disease (9,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) .…”

“…Liver biopsy is not the gold standard, but it can contribute to the diagnosis, especially in countries like Brazil (4) , where phenotyping or genotyping are unavailable in the public health system. Specificity of the diastasis resistant, PAS-positive granules finding can reach 94% in patients carrying the Z allele (12) .…”