Alpha-1 Antitrypsin Deficiency in Patients With Cirrhosis in a US National Cohort

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that increases susceptibility to chronic lung and liver diseases. There are limited data on testing rates in patients with cirrhosis. Guidelines recommend AATD testing in cryptogenic liver disease but not in patients with an established etiology. We aimed to quantify AATD testing patterns in a national cohort of patients with cirrhosis to inform guidelines.

In this retrospective cohort study of veterans with a new diagnosis of cirrhosis between January 1, 2008 and January 31, 2020, with follow-up until February 23, 2023, we identified predictors of testing, and of severe AATD (alpha-1 antitrypsin [AAT] < 57 mg/dL or PiSZ/PiZZ phenotype/genotype).

Of the 126,210 patients with cirrhosis, 42,403 (33.6%) were tested, including 38,189 (30.3%) for AAT levels only, 1,103 (0.8%) for genotype/phenotype only, and 3,011 (2.4%) for both. Factors associated with higher AATD testing included specialist evaluation and White race, whereas patients with chronic obstructive pulmonary disease, hepatitis B/C, hepatocellular carcinoma, and hepatic decompensation were less likely to be tested. Only half of the patients with AAT levels of <57 mg/dL underwent genotype/phenotype testing. Most patients (94.7%) with severe AATD-associated liver disease also had an alternate etiology of liver disease, including metabolic dysfunction associated with steatotic liver disease (53.6%) or viral hepatitis (16.1%), and would be missed if testing only patients with cryptogenic liver disease.

AATD testing rates in veterans with cirrhosis are low, and patients at high-risk are less likely to be tested. Guidelines are needed to emphasize universal AATD testing in patients with cirrhosis regardless of the presence of other risk factors.