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Jonas F. Ludvigsson, MD, PhD; Scott M. Montgomery, PhD; Anders Ekbom, MD, PhD; Lena Brandt, BSc; Fredrik Granath, PhD

JAMA. 2009;302(11):1171-1178.

Context  Studies of mortality in celiac disease have not taken small-intestinal pathology into account.

Objective  To examine mortality in celiac disease according to small-intestinal histopathology.

Design, Setting, and Patients  Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29 096 individuals) and inflammation (Marsh stage 1-2; n = 13 306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population.

Main Outcome Measure  All-cause mortality.

Results  There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat.

Conclusion  Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.

Author Affiliations: Department of Pediatrics (Dr Ludvigsson) and Clinical Research Centre (Dr Montgomery), Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden (Drs Ludvigsson, Montgomery, Ekbom, and Granath and Ms Brandt); and Department of Primary Care and Social Medicine, Charing Cross Hospital, Imperial College, London, England (Dr Montgomery).

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