Systematic review with meta-analysis: Cause-specific and all-cause mortality trends across different coeliac disease phenotypes.

Background: Data on mortality in coeliac disease are contrasting.

Aims: To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time.

Methods: We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN).

Results: We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I  = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I  = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I  = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I  = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I  = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I  = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I  = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I  = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I  = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I  = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I  = 81%). Limitations include high heterogeneity and lack of data for many countries.

Conclusion: Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.