Patients with celiac disease face an increased risk of developing any chronic liver disease. This risk increase can persist for at least 25 years after celiac diagnosis. The findings, published in The Lancet Regional Health—Europe, underscore clinical vigilance for signs of liver disease in patients with celiac disease to prevent major adverse liver outcomes.

The researchers identified more than 48,000 patients with biopsy-confirmed celiac disease in the Swedish ESPRESSO cohort and over 231,000 matched general population reference individuals between 1969 and 2017.

During a median follow-up of 16 years, patients with celiac disease were at a two-fold increased risk of developing any chronic liver disease than matched reference individuals from the general population.

The elevated risk persisted, leading to one extra case of chronic liver disease per 110 patients during 25 years after celiac disease diagnosis. Patients with celiac disease who had concurrent autoimmune or metabolic-related diseases had further heightened risks.

"The absolute risk difference for any chronic liver disease between patients with celiac disease and the reference individuals was small," says the study's first author Jialu Yao, Ph.D. student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.

"However, the relative risks for autoimmune liver disease and metabolic dysfunction-associated steatotic liver disease stood out among investigated chronic liver disease with point estimates being 4.86 and 2.54, respectively."

Recommended monitoring

The findings align with current guidelines recommending liver enzyme monitoring in the medical follow-up of patients with celiac disease.

"In addition to being vigilant to signs of progressive liver disease, clinicians working with patients with celiac disease should inform them about risk factors of chronic liver disease and be attentive to metabolic parameters when they initiate a gluten-free diet," says senior author Jonas F. Ludvigsson, professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and pediatrician at Örebro University Hospital.

"Being attentive to liver disease risk factors may be particularly important for patients with a history of autoimmune or metabolic-related diseases."

"The positive association between celiac disease and chronic liver disease may be mediated by genetic and immunological factors or the side effect of a gluten-free diet with unbalanced nutritional content," says Jialu Yao.

"Further research should focus on the underlying mechanisms and the hepatic impact of a gluten-free diet to guide better clinical care."

More information: Jialu Yao et al, Long-term risk of chronic liver disease in patients with celiac disease: a nationwide population-based, sibling-controlled cohort study, The Lancet Regional Health - Europe (2025). DOI: 10.1016/j.lanepe.2024.101201