30-year mortality of individuals with α1-antitrypsin deficiency: A Nationwide cohort study

<bold>Background:</bold> Long-term mortality may be higher in people with alpha-1 antitrypsin deficiency (AATD). <bold>Methods:</bold> We identified 2712 individuals diagnosed with AATD from 1969 to 2018 and compared them to 26844 persons from the general population matched by age, sex and municipality. We recorded deaths and comorbidities during follow-up using the national Danish Register of Causes of Death and the Danish National Patient Registry. Mortality rate ratios were assessed using cox regression analysis adjusted for age, sex and employment status. <bold>Results:</bold> The mortality risks for people with AATD were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (18% vs 1.6%). The 30-year mortality rate ratio was 2.38 ([95% CI: 2.21-2.56]) in people with AATD overall, 3.25 ([2.98-3.54]) in patients with AATD and COPD, and 7.04 ([5.32-9.32]) in patients with AATD and liver cirrhosis. The overall 1-10 year and 11-30 year mortality rate ratios improved from 3.75 ([3.23-4.36]) and 3.00 ([2.60-3.47]) in 1969 to 1995 to 1.49 ([1.31-1.70]) and 1.67 ([1.36-2.05]) in 1996-2018, respectively. A similar pattern was seen for patients with AATD and COPD (4.66[3.98-5.46] and 4.26[3.61-5.04] vs 2.03[1.75-2.36] and 2.37[1.87-2.99]), but not in patients with AATD and liver cirrhosis (4.39[2.68-7.20] and 4.06[2.66-6.18] vs 5.61[3.45-9.11] and 3.36[1.11-10.2]). <bold>Conclusions:</bold> People with alpha-1 antitrypsin deficiency have an increased risk of dying, particularly within the first year after diagnosis or if they have liver cirrhosis or COPD. Mortality beyond 1 year has improved for people with AATD in Denmark, but not for those patients who have comorbid liver cirrhosis.