Published online Oct 27, 2023. doi: 10.4254/wjh.v15.i10.1127
Peer-review started: May 22, 2023
First decision: July 8, 2023
Revised: August 11, 2023
Accepted: September 18, 2023
Article in press: September 18, 2023
Published online: October 27, 2023
Processing time: 154 Days and 18.2 Hours
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that can result in the development of liver and/or lung disease, and is a leading cause of inherited alterations in plasma protein metabolism (APPM).
Currently, there is a lack of information on the natural history and epidemiology of AATD.
To understand the prevalence, burden and progression of liver disease in patients with APPM, which includes patients diagnosed with AATD, in Germany.
A retrospective analysis of anonymized, patient-level, insurance claims data from a German health insurance provider (AOK PLUS) was conducted. The APPM cohort comprised patients with APPM (01/01/2010-30/09/2020) and incident liver disease (01/01/2012-30/09/2020) and the control cohort comprised patients without APPM but with incident liver disease. Outcomes were incidence/prevalence of liver disease in patients with APPM, demographics/baseline characteristics, disease progression, progression-free survival, mortality, and diagnostic procedures.
Overall, 2680 and 26299 patients were included in the APPM [fibrosis (96); cirrhosis (2584)] and control [fibrosis (1444); cirrhosis (24855)] cohorts, respectively. The annual incidence and prevalence of APPM and liver disease was 10-15/100000 and 36-51/100000, respectively. Median survival was shorter in the APPM cohort (2.6 years) than in the control cohort (4.3 years). In patients in the APPM cohort with fibrosis and cirrhosis, respectively, median survival was 4.7 years and 2.5 years. More patients in the APPM cohort (92.0%) experienced liver disease progression than in the control cohort (67.2%). Median progression-free survival was shorter in the APPM cohort [0.9 years (95%CI: 0.7-1.1)] compared with the control cohort [3.7 years (95%CI: 3.6-3.8); P < 0.001]. In patients with cirrhosis, event-free survival for ascites, hepatic encephalopathy, hepatic failure, and esophageal/gastric varices was longer in the control cohort than in the APPM cohort (P < 0.001). In patients with fibrosis, event-free survival for ascites, cirrhosis, hepatic failure, and esophageal/gastric varices was longer in the control cohort than in the APPM cohort (P < 0.001). The most common diagnostic procedures within 12 mo after the first diagnosis of liver disease in the APPM cohort were imaging procedures (66.3%) and laboratory tests (51.0%).
In Germany, patients with APPM and liver disease experience substantial burden and a higher rate of and earlier liver disease progression than patients without APPM.
The adoption of diagnosis codes specific to AATD should enable differentiation of this disease from other APPM disorders and facilitate earlier diagnosis and patient management. This should contribute to slowing disease progression and decreasing the burden of disease in patients with this rare, chronic disease.