Researchers discovered that smoking history was associated with disease progression in patients with PI*ZZ alpha-1 antitrypsin deficiency (AATD), as published in the European Journal of Gastroenterology & Hepatology.

Alpha-1 antitrypsin (AAT) is a serine protease inhibitor that neutralizes neutrophil elastase. In AATD, the lack of AAT means that the activity of neutrophil elastase remains unopposed, causing emphysema.

AATD is inherited in an autosomal codominant manner. The 2 most common mutations in the AAT gene are designated PI*Z and PI*S.


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“Because the Z AAT protein polymerizes within the hepatocyte, the PI*ZZ genotype is associated with intrahepatic accumulation of unsecreted ZZ AAT, resulting in a toxic gain of function, which predisposes to liver disease and a toxic loss of function in the lung, predisposing to emphysema,” the authors of the study wrote.

AATD is a disease that remains under-recognized; scientists estimated that less than 15% of patients with this disease are diagnosed with it. Even if AATD is diagnosed, the factors driving its progression are poorly understood. The authors of this study hence decided to investigate whether 3 factors are associated with liver or lung disease progression in AATD: age, sex, and smoking status.

Read more about AATD etiology 

They assembled a cohort of 43 patients who had cirrhosis due to PI*ZZ AATD. They used statistical analysis to determine whether age, sex, or smoking status were risk factors for transplant status or increased progression of lung or liver disease among recruited patients.

“Our study of 43 ZZ-AATD individuals with cirrhosis followed at the Cleveland Clinic showed that smoking history was significantly associated with liver disease progression, whereas age and sex were not,” the authors said. 

The discovery that smoking history drives disease progression in AATD invites further prospective studies to validate those results. Since the present study only involved 43 patients, larger studies involving more patients may give clinicians a better view of the various risk factors for disease progression in AATD.

Reference

Shen K, Lyu R, Sengupta S, Wakim-Fleming J. Disease progression in patients with PI*ZZ alpha-1 antitrypsin deficiencyEur J Gastroenterol Hepatol. 2022;34(8):852-856. doi:10.1097/MEG.0000000000002395