ArticlePloS one2021
Quantitative measurement of the histological features of alpha-1 antitrypsin deficiency-associated liver disease in biopsy specimens.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- RNA editing for the treatment of alpha-1 antitrypsin deficiency.Nucleic acids research · 2026Article
- Protein Aggregates in Heterozygous Alpha-1 Antitrypsin Phenotype Is a Marker for Progressive Disease.Gastro hep advances · 2026Article
- Case Report: α1-antitrypsin deficiency causing persistent pleural effusion and multilobar alveolar emphysema in a young dog.Frontiers in veterinary science · 2025Article
- Berberine potentiates liver inflammation and fibrosis in the PI*Z hAAT transgenic murine model.PloS one · 2024Article
- Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.International journal of molecular sciences · 2023Article
- The unfolded protein response to PI*Z alpha-1 antitrypsin in human hepatocellular and murine models.Hepatology communications · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPathological mutations in Alpha-1 Antitrypsin (AAT) protein cause retention of toxic polymers in the hepatocyte endoplasmic reticulum. The risk for cirrhosis in AAT deficiency is likely directly related to retention of these polymers within the liver. Polymers are classically identified on liver biopsy as inclusion bodies by periodic acid schiff staining after diastase treatment and immunohistochemistry. However, characterization of the polymer burden within a biopsy sample is limited to a semi-quantitative scale as described by a pathologist. Better methods to quantify polymer are needed to advance our understanding of pathogenesis of disease. Therefore, we developed a method to quantify polymer aggregation from standard histologic specimens. In addition, we sought to understand the relationship of polymer burden and other histologic findings to the presence of liver fibrosis.
methodsLiver samples from a well-categorized AATD cohort were used to develop histo-morphometric tools to measure protein aggregation.
resultsWhole-slide morphometry reliably quantifies aggregates in AATD individuals. Despite very low levels of inclusions present (0-0.41%), accumulation of globules is not linear and is associated with higher fibrosis stages. Immunohistochemistry demonstrates that fibrosis is associated with polymer accumulation and not total AAT. A proportion of patients were found to be "heavy accumulators" with a polymer burden above the upper 25% of normal distribution. Males had significantly more liver inclusions and polymer than females. These measurements also highlight interrelated phenotypes of hepatocellular degeneration and autophagy in AATD liver disease.
conclusionQuantitative inclusion analysis measures AAT accumulation in liver biopsy specimens. Quantification of polymer may identify individuals at risk for progressive disease and candidates for therapeutic interventions. Furthermore, these methods may be useful for evaluating efficacy of drugs targeting accumulation of AAT.
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