Celiac Disease Linked to Greater Long-Term Incident Chronic Liver Disease Risk

Individuals with celiac disease have a 2-fold increased relative risk of developing incident chronic liver disease (CLD) relative to the general population, according to findings from a recent study.1

The nationwide cohort study included nearly 50,000 patients with biopsy-confirmed celiac disease from the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort, with results highlighting autoimmune liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-related liver disease as drivers of the heightened long-term risk of CLD.1

“Despite growing evidence for a positive association between celiac disease and CLD, most longitudinal studies are outdated with follow-ups ending 15 to 30 years ago,” Jonas Ludvigsson, MD, a professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet and a senior physician at the Children's Clinic at Örebro University Hospital, and colleagues wrote.1 “Little is known about the risks for CLD of some specific etiologies, or major adverse liver outcomes.”

Celiac disease is a chronic digestive and immune disorder that damages the small intestine and is triggered by eating foods containing gluten. Other disorders related to the immune system, including various liver diseases, are common in patients with celiac disease, as is long-term liver damage leading to cirrhosis and liver failure.2

To investigate the long-term risk of CLD in patients with celiac disease, investigators conducted a nationwide population-based cohort study of 48,027 patients with biopsy-confirmed celiac disease in the ESPRESSO cohort, a histopathology cohort which collects gastrointestinal biopsy reports from all 28 pathology departments in Sweden beginning in 1965 and updated through 2017.1

For inclusion, patients were required to be living in Sweden and have villus atrophy in the small intestine other than the ileum between 1969 and 2017. Each eligible patient with celiac disease was matched with up to 5 general population reference individuals from the Total Population Register by sex, birth year, calendar year of index date, and county of residence.1

The primary outcome was any incident CLD. Secondary outcomes included specific CLD by etiology and major adverse liver outcomes (MALO), a composite endpoint for compensated or decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, or liver-related death.1

For each outcome, investigators followed individuals from the index date until the first diagnosis of the outcome of interest, emigration, death, or the end of study in December 2021.1

Among the cohort with celiac disease, the majority of patients were female (62.7%), their median age at diagnosis was 27.3 years, and 40.7% were diagnosed when they were <18 years of age. They were compared with a cohort of 231,909 reference individuals.1

During a median follow-up of 16 years, 649 patients with celiac disease and 1571 reference individuals developed any CLD (incidence rate [IR], 79.4 vs 39.5 per 100,000 person-years).1

After multivariable adjustment, investigators noted patients with celiac disease had a 2-fold increased risk of developing any CLD (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.82-2.22) compared to reference individuals. The HR of any CLD was greatest immediately after the diagnosis and remained elevated 25 years after diagnosis.1

Further analysis revealed patients with celiac had higher absolute and relative risks of autoimmune liver disease (IR, 35.9 vs 6.8 per 100,000 person-years; aHR, 4.86; 95% CI, 4.06 to 5.82). Additionally, investigators pointed out an increased risk of MASLD (IR, 16.4 vs. 6.5 per 100,000 person-years; aHR, 2.54; 95% CI, 2.03-3.18) and alcohol-related liver disease (IR, 13.3 vs 9.1 per 100,000 person-years; aHR, 1.51; 95% CI, 1.20-1.90), but not viral hepatitis (IR, 16.3 vs 18.3 per 100,000 person-years; aHR, 0.89; 95% CI, 0.73-1.10), among those with celiac disease.1

During follow-up, 580 individuals with celiac disease developed MALO events compared with 1795 among reference individuals, yielding an aHR of 1.54 (95% CI, 1.40-1.70). The most frequent event was compensated or decompensated cirrhosis (IR, 61.8 vs. 38.5 per 100,000 person-years; aHR, 1.60; 95% CI, 1.44-1.78).1

“Clinicians should be vigilant to signs of progressive liver disease such as elevated liver enzymes in patients with celiac disease to prevent the long-term risk of developing MALO,” investigators concluded.1

References

1. Yao J, Sun J, Ebrahimi F, et al. Long-term risk of chronic liver disease in patients with celiac disease: a nationwide population-based, sibling-controlled cohort study. Lancet Reg Health Eur. doi:10.1016/j.lanepe.2024.101201

2. National Institute of Diabetes and Digestive and Kidney Diseases. Definition & Facts for Celiac Disease. October 2020. Accessed March 18, 2025. https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease/definition-facts