Introduction
Trypsin is a proteolytic enzyme produced in the gastrointestinal system.1 Counterbalancing trypsin is its inhibitor, alpha-1 antitrypsin (AAT), predominantly produced in the liver.2 AAT plays a role as a protector in a variety of physiological processes throughout the body.
AAT deficiency (AATD) is inherited through autosomal codominant transmission. The most severe AAT deficiency results from Z allele homozygosity. Based on a patient’s genotype, the combination of alleles, and their environment, patients express different phenotypes or observable clinical characteristics.3 AATD primarily affects the lungs and manifests as emphysema, chronic obstructive pulmonary disease (COPD) and other respiratory conditions (eg, asthma). In the liver, disease results from accumulation within the hepatocytes of unsecreted, abnormal, variant AAT protein. This accumulation causes cytotoxicity that can manifest early as neonatal liver disease or in adulthood as progressive liver disease.2
AATD is largely unrecognised.4 In fact, previous studies, including one in Denmark, estimate that less than 25% of those with this hereditary condition are diagnosed.5 6 Hence, in general population studies, it is important to differentiate genetic AATD from diagnosed AATD (dAATD). Diagnosed AATD includes both symptomatic cases and to a lesser extent those detected through screening, the latter showing mortality more in line with general population rates.7 Because dAATD is rare, its frequency and sequalae are most efficiently studied with healthcare database studies, provided the databases are of acceptable quality. A recent study in Germany using a health insurance database that included approximately 87% of the country’s population reported the prevalence to be 24 per 100 000 persons.8 Prevalence estimates can vary appreciably across studies, reflecting variations in country-specific prevalence, screening activities, data sources, case definitions and analytical methods, especially the length of the disease lookback period.9 This study focuses on the Danish national population and capitalises on the availability of lifelong, high-quality health registry data for all residents for the last several decades.10 11
Study objectives
The primary objective was to estimate the prevalence of dAATD in Denmark as of 31 December 2018. We defined prevalence as the number of patients with dAATD per 100 000 Danish residents, who were alive as of 31 December 2018, regardless of how long ago their AATD diagnosis was made.
Secondary objectives were to estimate dAATD incidence and all-cause mortality for patients with dAATD and to compare mortality rates for patients with dAATD to rates for a general population cohort matched on age and sex. Finally, we characterised patients with dAATD with respect to respiratory disease, hepatic disease and related comorbidities.