Exosomes could provide valuable information for diagnosing alpha-1 antitrypsin deficiency (AATD), according to a new study that will be presented at the 2022 The Liver Meeting.

In particular, the analysis of microRNA (miRNAs) and mitochondrial RNA content might allow for the identification of AATD individuals with liver injury, overcoming the need for an invasive procedure, such as biopsy.

“The plasma exosome profile of AATD individuals has distinct features that differentiate them from those of healthy controls, reflecting pathophysiology of AATD liver disease,” said Nazli Khodayari, author of the study.

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Those with AATD showed higher plasma concentrations of injured liver-derived exosomes than healthy controls as demonstrated by the quantification of asialoglycoprotein receptor 1-expressing exosomes. Moreover, the content of plasma exosomes differed not only between AATD individuals and healthy controls but also within AATD groups at different stages of liver disease.

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RNA sequencing studies identified 105 miRNAs and 8 mitochondrial RNAs that were differentially expressed between AATD individuals and healthy controls. Of those, 63 miRNAs and 7 mitochondrial RNAs were upregulated, while 42 miRNAs and 1 mitochondrial RNA were downregulated. Moreover, 54 and 35 miRNAs were positively and negatively associated with disease score, respectively, whereas 38 and 30 miRNAs were positively and negatively associated with fibrosis, respectively.

The study enrolled 17 individuals with AATD at different stages of liver disease and 20 healthy controls. The characterization of plasma exosomes was performed by nanoparticle tracking analysis, flow cytometry, and RNA sequencing.

There is an urgent need for reliable biomarkers that could identify the disease in the earlier presymptomatic stages, as most commonly, liver disease in AATD patients is silent until advanced fibrosis is established. AATD predisposes to many diseases such as emphysema and other chronic lung diseases, as well as cirrhosis and hepatocellular carcinoma.


Khodayari N. Novel biomarkers for Z alpha 1-antitrypsin mediated liver disease in circulating exosomes. Hepatology. 2022;76(S1):S1110.