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, I2 = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08–1.36, I2 = 65%) and respiratory disease (HR 1.39, 95% CI 1.04–1.86, I2 = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19–46.88, I2 = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989–2004 (HR 1.61, 95% CI 1.27–2.03, I2 = 91%), 2005–2014 (HR 1.16, 95% CI 0.99–1.36, I2 = 89%), 2015–2022 (HR 1.19, 95% CI 1.05–1.35, I2 = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73–0.99, I2 = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95–1.25, I2 = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03–1.47, I2 = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91–1.13, I2 = 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.