Long-term risk of chronic liver disease in patients with celiac disease: a nationwide population-based, sibling-controlled cohort study
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Updated: May 22, 2025
The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury
Published on: October 21, 2017
Jialu Yao1, Jiangwei Sun1, Fahim Ebrahimi1,2
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Background:
Celiac disease (CeD) may be associated with elevated liver enzymes. However, little is known about the risk of chronic liver disease (CLD) of various etiologies or major adverse liver outcomes (MALO) in CeD. We aimed to investigate the long-term risk of CLD in patients with CeD.
Methods:
Swedish nationwide cohort study. We identified 48,027 patients with biopsy-confirmed CeD between 1969 and 2017. Each patient was exactly matched with ≤5 general population reference individuals (n = 231,909) and followed through 2021. Flexible parametric survival models estimated adjusted hazard ratios (aHRs) of any and specific CLD (i.e., viral hepatitis, metabolic dysfunction-associated steatotic liver disease [MASLD], alcohol-related liver disease, and autoimmune liver disease) and MALO (compensated/decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death).
Findings:
During a median follow-up of 16.0 years, 649 patients with CeD and 1571 reference individuals developed any CLD (incidence rate: 79.4 vs. 39.5/100,000 person-years). CeD patients had a higher risk of developing any CLD than reference individuals (aHR = 2.01, 95%CI:1.82-2.22). This risk remained elevated ≥25 years after diagnosis, giving one extra CLD case per 110 CeD patients until then. Positive associations were present for autoimmune liver disease (aHR = 4.86), MASLD (aHR = 2.54), and alcohol-related liver disease (aHR = 1.51). Individuals with CeD were at significantly higher risk of incident MALO (aHR = 1.54). Sibling comparisons and sensitivity analyses confirmed the main findings.
Interpretation:
CeD is associated with a persistently increased risk of any incident CLD, although the absolute risk is low. Physicians should be vigilant to early signs of liver dysfunction in patients with CeD.
Funding:
European Crohn's and Colitis Organisation, the Swedish Society for Medical Research (project#: PG-23-0315-H-02), FORTE (project#: 2016-00424), Takeda, and the Swiss National Science Foundation (project#: P500PM_210866).
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