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Severe α1-Antitrypsin Deficiency and Increased Risk of Gastrointestinal Diseases

Hiller, Adriana-Maria LU orcid ; Piitulainen, Eeva LU ; Ekström, Magnus LU orcid ; Lindberg, Anne ; Rönmark, Eva and Tanash, Hanan LU (2026) In Mayo Clinic Proceedings
Abstract
Objective
To determine whether the genetic disorder severe α1-antitrypsin deficiency, which has a known association with increased risk for development of lung and liver diseases, is also associated with increased risk for development of gastrointestinal diseases.

Patients and Methods
We conducted a national, longitudinal, registry-based study of individuals with severe α1-antitrypsin deficiency (phenotype PiZZ; n=1561) and controls (n=5964) who were part of Swedish population-based cohorts between January 1,1991, through January 1, 2015. Data on gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its... (More)
Objective
To determine whether the genetic disorder severe α1-antitrypsin deficiency, which has a known association with increased risk for development of lung and liver diseases, is also associated with increased risk for development of gastrointestinal diseases.

Patients and Methods
We conducted a national, longitudinal, registry-based study of individuals with severe α1-antitrypsin deficiency (phenotype PiZZ; n=1561) and controls (n=5964) who were part of Swedish population-based cohorts between January 1,1991, through January 1, 2015. Data on gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), hospitalizations, and mortality were obtained by cross-linkage with national registries. Risk factors for development of gastrointestinal diseases were analyzed using Cox proportional hazards models and Fine-Gray regression models, adjusted for baseline age, sex, smoking status, the presence of chronic obstructive pulmonary disease, and liver diseases.

Results
During a median follow-up of 10 years (IQR, 11 years) for the whole study population, the incidence rate of any gastrointestinal disease per 1000 person-years was 10.6 (95% CI, 9.0 to 12.4) for the individuals with the PiZZ phenotype and 3.6 (95% CI, 3.2 to 4.1) for the controls, with an adjusted hazard ratio (aHR) of 2.7 (95% CI, 2.1 to 3.4). Individuals with PiZZ had an increased risk of Crohn disease (aHR, 4.1; 95% CI, 2.0 to 8.4), ulcerative colitis (aHR, 4.6; 95% CI, 2.4 to 8.6), noninfectious gastroenteritis (aHR, 2.6; 95% CI, 1.3 to 5.2), and diverticular disease (aHR, 2.1; 95% CI, 1.5 to 2.9).

Conclusion
Individuals with PiZZ have an increased risk for development of gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), as compared with the general population. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
in press
subject
in
Mayo Clinic Proceedings
publisher
Elsevier
external identifiers
  • pmid:41885682
ISSN
0025-6196
DOI
10.1016/j.mayocp.2025.11.017
language
English
LU publication?
yes
id
2657eea9-a2ec-4b0f-86a2-b2b9b7d9c724
alternative location
https://linkinghub.elsevier.com/retrieve/pii/S0025619625181585
date added to LUP
2026-04-02 09:24:19
date last changed
2026-04-03 03:00:02
@article{2657eea9-a2ec-4b0f-86a2-b2b9b7d9c724,
  abstract     = {{Objective<br/>To determine whether the genetic disorder severe α1-antitrypsin deficiency, which has a known association with increased risk for development of lung and liver diseases, is also associated with increased risk for development of gastrointestinal diseases.<br/><br/>Patients and Methods<br/>We conducted a national, longitudinal, registry-based study of individuals with severe α1-antitrypsin deficiency (phenotype PiZZ; n=1561) and controls (n=5964) who were part of Swedish population-based cohorts between January 1,1991, through January 1, 2015. Data on gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), hospitalizations, and mortality were obtained by cross-linkage with national registries. Risk factors for development of gastrointestinal diseases were analyzed using Cox proportional hazards models and Fine-Gray regression models, adjusted for baseline age, sex, smoking status, the presence of chronic obstructive pulmonary disease, and liver diseases.<br/><br/>Results<br/>During a median follow-up of 10 years (IQR, 11 years) for the whole study population, the incidence rate of any gastrointestinal disease per 1000 person-years was 10.6 (95% CI, 9.0 to 12.4) for the individuals with the PiZZ phenotype and 3.6 (95% CI, 3.2 to 4.1) for the controls, with an adjusted hazard ratio (aHR) of 2.7 (95% CI, 2.1 to 3.4). Individuals with PiZZ had an increased risk of Crohn disease (aHR, 4.1; 95% CI, 2.0 to 8.4), ulcerative colitis (aHR, 4.6; 95% CI, 2.4 to 8.6), noninfectious gastroenteritis (aHR, 2.6; 95% CI, 1.3 to 5.2), and diverticular disease (aHR, 2.1; 95% CI, 1.5 to 2.9).<br/><br/>Conclusion<br/>Individuals with PiZZ have an increased risk for development of gastrointestinal diseases (Crohn disease, ulcerative colitis, noninfectious gastroenteritis, and diverticular disease encompassing symptomatic diverticulosis and its complications), as compared with the general population.}},
  author       = {{Hiller, Adriana-Maria and Piitulainen, Eeva and Ekström, Magnus and Lindberg, Anne and Rönmark, Eva and Tanash, Hanan}},
  issn         = {{0025-6196}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Elsevier}},
  series       = {{Mayo Clinic Proceedings}},
  title        = {{Severe α1-Antitrypsin Deficiency and Increased Risk of Gastrointestinal Diseases}},
  url          = {{http://dx.doi.org/10.1016/j.mayocp.2025.11.017}},
  doi          = {{10.1016/j.mayocp.2025.11.017}},
  year         = {{2026}},
}