Mayo Clinic proceedings · 2026
Severe α1-Antitrypsin Deficiency and Increased Risk of Gastrointestinal Diseases.
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Hiller Adriana-Maria, Piitulainen Eeva, Ekström Magnus, Lindberg Anne, Rönmark Eva, Tanash Hanan
Аннотация
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.
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.