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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Liver disease epidemiology and burden in patients with alterations in plasma protein metabolism: German retrospective insurance claims analysis
Nils Picker, May Hagiwara, Severin Baumann, Ed G Marins, Thomas Wilke, Kaili Ren, Ulf Maywald, Chitra Karki, Pavel Strnad
Nils Picker, Severin Baumann, Real-World Evidence, Cytel Inc. Ingress-Health HWM GmbH, Wismar 23966, Germany
May Hagiwara, Chitra Karki, R&D, Global Evidence and Outcomes, Takeda Development Center Americas, Inc., Cambridge, MA 02139, United States
Ed G Marins, Global Medical Affairs, Takeda Development Center Americas, Inc., Cambridge, MA 02139, United States
Thomas Wilke, IPAM Institute, IPAM E.V., Wismar 23966, Germany
Kaili Ren, Statistics and Quantitative Sciences, Data Science Institute, Takeda Development Center Americas, Inc., Cambridge, MA 02139, United States
Ulf Maywald, Drug Department, AOK PLUS, Dresden 01058, Germany
Pavel Strnad, Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen 52074, Germany
Author contributions: Picker N, Hagiwara M, Baumann S, Marins EG, Wilke T, Ren K, Maywald U, Karki C, and Strnad P provided substantial contribution to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work, and drafted the work or revised it critically for important intellectual content; all authors provided final approval of the version to be published; all authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Institutional review board statement: Institutional review board approval was not required for this retrospective analysis of anonymized data.
Informed consent statement: Signed informed consent forms were not required as this was a retrospective analysis of anonymized data.
Conflict-of-interest statement: Dr. Strnad reports grants and other from CSL Behring, grants and other from Grifols, grants and other from Arrowhead Pharmaceuticals, grants and other from Dicerna Pharmaceuticals, grants from Vertex Pharmaceuticals, other from Albireo, other from GlaxoSmithKline, other from Intellia Pharmaceuticals, other from Ono Pharmaceuticals, other from Takeda Pharmaceuticals, during the conduct of the study.
Data sharing statement: The data that support the findings of this study are available from AOK PLUS. Restrictions apply to the availability of these data, which were used under license for this study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Pavel Strnad, MD, Professor, Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, 30 Pauwelsstraße, Aachen 52074, Germany. pstrnad@ukaachen.de
Received: May 22, 2023
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
ARTICLE HIGHLIGHTS
Research background
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).
Research motivation
Currently, there is a lack of information on the natural history and epidemiology of AATD.
Research objectives
To understand the prevalence, burden and progression of liver disease in patients with APPM, which includes patients diagnosed with AATD, in Germany.
Research methods
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.
Research results
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%).
Research conclusions
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.
Research perspectives
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.
