There may be a link between levels of circulating Z-alpha-1 antitrypsin (Z-AAT), the misfolded version of alpha-1 antitrypsin protein causing alpha-1 antitrypsin deficiency (AATD), and liver function, according to a new study published in Biomolecules.

This finding suggests that circulating Z-AAT polymers could be used as a biomarker to predict clinically important outcomes in patients with AATD, although more studies are needed.

To assess whether levels of circulating Z-AAT polymers are associated with the severity of lung disease, liver disease, or both, a team of researchers led by Jan Stolk, PhD, from the Department of Pulmonology at Leiden University Medical Center in the Netherlands conducted a study on data they obtained from the Dutch part of the Alpha One International Registry and the Alpha-1 Liver Aachen Registry.

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A total of 52 patients from the Alpha One International Registry who were homozygous for the Z allele of the SERPINA1 gene encoding alpha-1 antitrypsin (ZZ-AAT) donated a blood sample and performed a lung function test on the same day. The researchers also obtained data about the liver function of 40 patients with ZZ-AAT from the Alpha-1 Liver Aachen Registry.

They found that the median level of Z-AAT polymers in the plasma of patients with pulmonary disease in the Alpha One International Registry was 947.5 µg/mL. This did not correlate with airflow obstruction or the value for gas transfer.

For patients in the Alpha-1 Liver Aachen Registry, the median level of Z-AAT polymers was 1245.9 µg/mL. This did correlate with plasma gamma-glutamyl transferase, glutamate dehydrogenase, and triglyceride levels.

“A Wilcoxon rank test showed higher Z-AAT polymer values for the liver over the lung group,” the researchers wrote and concluded that these correlations support a possible link between Z-AAT polymers in the blood and liver function.


Sark AD, Fromme M, Olejnicka B, et al. The relationship between plasma alpha-1-antitrypsin polymers and lung or liver function in ZZ alpha-1-antitrypsin-deficient patients. Biomolecules. 2022;12(3):380. doi:10.3390/biom12030380