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

Background: Data on mortality in celiac disease are contrasting.
Aims: To systematically review the literature on all-cause and cause-specific mortality in celiac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time.
Methods: The authors searched PubMed and Embase from January 1, 1970, to December 31, 2022, for eligible studies reporting on all-cause and cause-specific mortality in celiac disease compared to the general population or controls.
Results: They included 25 studies. All-cause mortality (hazard ratio [HR] = 1.16, 95% confidence interval [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 celiac disease (HR = 1.09, 95% CI: 0.95–1.25, I² = 0%). Mortality was increased in the United Kingdom (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 celiac disease is increased, predominantly due to malignancies – particularly non-Hodgkin lymphoma – although differing significantly across disease phenotypes. Mortality of patients with celiac disease has significantly decreased in recent decades. These results may influence diagnosis and management.

Dr. A. Schiepatti, Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy, E-Mail: annalisa.schiepatti01@universitadipavia.it

DOI: 10.1111/apt.17867

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