MASLD, MetALD Cardiometabolic Risk Factors Linked to Increased Long-Term Risk of IBD

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatotic liver disease with increased alcohol intake (MetALD) are associated with an increased risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), according to findings from a recent study.1

Leveraging data from the UK Biobank, the study found patients with MASLD were at an increased risk of developing incident IBD compared with those without MASLD. Findings also point to a greater risk of IBD as the number of cardiometabolic risk factors increases, including overweight/obesity, dysglycemia, hypertension, and dyslipidemia.1

“Increasing evidence has shown that individuals with steatotic liver disease have a higher risk of incident IBD than the general population in prospective cohort studies… However, these studies did not take into account the effect of alcohol intake or the number of cardiometabolic risk factors and only considered the effect of hepatic steatosis,” Shanshan Wu, an associate professor at Beijing Friendship Hospital, Capital Medical University in China, and colleagues wrote.1

MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), is estimated to affect more than 30% of the global population.2 IBD frequently occurs in patients with MASLD, mediated by the gut-liver axis, but research regarding the impact of MASLD etiology and cardiometabolic risk factors is sparse.1

To assess the association between MASLD and the risk of incident IBD, investigators examined data from the UK Biobank for 403,520 participants without cancer, IBD, alcohol-associated liver disease, or hepatitis B/C virus. MASLD at baseline was defined as fatty liver index (FLI) ≥ 60 with ≥ 1 cardiometabolic risk factor.1

Investigators further classified individuals with MASLD as having either pure MASLD, defined as MASLD with no alcohol intake or a weekly alcohol intake < 140 g in females and < 210 g in males, or MetALD, defined as MASLD with weekly alcohol intake of 140-350 g in females and 210-420 g in males.1

The primary outcome was incident IBD, including UC and CD, which was ascertained based on linkage to primary care and hospital inpatient data. Participants were followed from baseline until the date of IBD diagnosis, date of death, loss to follow-up, or May 31, 2022.1

Among the cohort (n = 403,520), the mean age was 56.2 ± 8.1 years and 45.6% of participants were male. In total, 37.6% of individuals had MASLD at baseline.1

During a median 13 years of follow-up, 2398 IBD cases were identified. The incidence rates of IBD, UC, and CD were 45.8 (95% CI, 44.0–47.6), 32.8 (95% CI, 31.3–34.4), and 15.9 (95% CI, 14.9–17.0) per 100,000 person-years, respectively.1

Upon analysis, having MASLD was associated with a significantly increased ris of incident IBD (Hazard ratio [HR], 1.39; 95% CI, 1.21–1.60), UC (HR, 1.34; 95% CI, 1.13–1.58), and CD (HR, 1.51; 95% CI, 1.20–1.89). Investigators noted these results were consistent in patients with pure MASLD (HR, 1.43; 95% CI, 1.23–1.66) and MetALD (HR, 1.46; 95% CI, 1.15–1.86) and pointed out the risk of IBD increased as the number of cardiometabolic risk factors increased (Ptrend <.001).1

“These findings emphasize the important role that metabolic dysfunction and cardiometabolic factors may play in IBD development,” investigators concluded.1

References

1. Zhang Q, Xu F, Whang Z, et al. Long-Term Risk of Inflammatory Bowel Disease With MASLD: A Large-Scale Prospective Cohort Study in UK Biobank. Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.16880
2. American Association for the Study of Liver Diseases. New MASLD Nomenclature. Accessed January 22, 2025. https://www.aasld.org/new-masld-nomenclature