Related Experiment Videos
Occurrence of alpha-1-antitrypsin deficiency in 155 patients with alcoholic liver disease
Abstract:
Liver biopsies from 155 patients with alcoholic liver disease were examined for periodic-acid-Schiff-positive, diastase-resistant (PAS-DR) intracytoplasmic globules in hepatocytes. Seven patients had these PAS-DR globules: each was a heterozygote for a deficiency allele of alpha-1-antitrypsin (AAT), or alpha-1-protease inhibitor, with the PAS-DR globules distributed in a pattern characteristic of this deficiency. One further patient with normal AAT had a few intracytoplasmic PAS-DR globules in occasional hepatocytes. The prevalence of AAT heterozygotes in this series did not differ from that in the reference population. The seven heterozygotes included five of PI (protease inhibitor) type MZ, one of PI type SZ, and one heterozygous for a rare deficiency allele, PI type MMmalton. The M and Mmalton alleles may be difficult to distinguish because they have similar mobilities with isoelectric focusing technics. Therefore, if PAS-DR inclusions are found in the liver of a patient with an apparently normal phenotype, the presence of a defective M variant allele, such as Mmalton, should be considered.
Insights
Periodic-acid-Schiff-positive, diastase-resistant globules in liver biopsies indicate alpha-1-antitrypsin (AAT) deficiency heterozygosity. Rare AAT variants, like Mmalton, may present with subtle globules, necessitating careful analysis in alcoholic liver disease patients.
Area of Science:
- Hepatology
- Genetics
- Biochemistry
Background:
- Alcoholic liver disease (ALD) can manifest with various histological features.
- Intracytoplasmic inclusions in hepatocytes may indicate underlying metabolic or genetic disorders.
- Alpha-1-antitrypsin (AAT) deficiency is a genetic condition affecting the liver and lungs.
Purpose of the Study:
- To investigate the presence and significance of periodic-acid-Schiff-positive, diastase-resistant (PAS-DR) intracytoplasmic globules in patients with ALD.
- To determine the association between these globules and alpha-1-antitrypsin (AAT) deficiency.
- To evaluate the diagnostic utility of PAS-DR globules for identifying AAT deficiency, including rare variants.
Main Methods:
- Examination of liver biopsies from 155 patients with ALD for PAS-DR intracytoplasmic globules.
- Genotyping and phenotyping of alpha-1-antitrypsin (AAT) in patients with and without globules.
- Analysis of globule distribution patterns and correlation with AAT deficiency alleles.
Main Results:
- Seven out of 155 ALD patients exhibited characteristic PAS-DR globules, all identified as AAT deficiency heterozygotes (PI types MZ, SZ, and MMmalton).
- One patient with normal AAT showed a few scattered PAS-DR globules.
- The prevalence of AAT heterozygotes in this cohort did not differ from the general population.
Conclusions:
- PAS-DR intracytoplasmic globules in hepatocytes are a significant indicator of alpha-1-antitrypsin (AAT) deficiency heterozygosity in patients with alcoholic liver disease.
- The presence of these globules, even in the absence of typical AAT deficiency phenotypes, warrants consideration of rare defective M variant alleles, such as Mmalton.
- Careful histological and genetic evaluation is crucial for diagnosing AAT deficiency, especially when subtle PAS-DR inclusions are observed in ALD patients.