NAFLD Is Associated With Quiescent Rather Than Active Crohn's Disease

Background and Aims Crohn's disease (CD) confers an increased risk of nonalcoholic fatty liver disease (NAFLD), but the pathogenesis remains poorly understood. We determined if active intestinal inflammation increases the risk of NAFLD in patients with CD. Methods Two cohorts (2017/2018 and 2020) with CD and no known liver disease were enrolled consecutively during staging magnetic resonance enterography. We quantified proton density fat fraction, MaRIA (Magnetic Resonance Index of Activity), and visceral adipose tissue. NAFLD was diagnosed when proton density fat fraction & GE;5.5%. Synchronous endoscopy was graded by the Simple Endoscopic Score for CD and Rutgeerts score, while clinical activity was graded by the Harvey-Bradshaw index. Cytokine profiling was performed for the 2020 cohort. Transient elastography and liver biopsy were requested by standard of care. Results NAFLD was diagnosed in 40% (n = 144 of 363), with higher prevalence during radiographically quiescent disease (odds ratio, 1.7; P = .01), independent of body mass index/visceral adipose tissue (adjusted odds ratio, 7.8; P = .03). These findings were corroborated by endoscopic disease activity, but not by aggregate clinical symptoms. Circulating interleukin-8 was independent of body mass index to predict NAFLD, but traditional proinflammatory cytokines were not. NAFLD subjects had similar liver stiffness estimates regardless of CD activity. Definitive or borderline steatohepatitis was present in most patients that underwent liver biopsy. Conclusions Quiescent CD is associated with risk of NAFLD. These findings suggest potentially distinct pathogenic mechanisms of NAFLD in patients with CD compared with the prevailing leaky gut hypothesis proposed for individuals without inflammatory bowel disease. Future validation and mechanistic studies are needed to dissect these distinct disease modifying factors. Lay Summary Crohn's disease patients had an independently increased risk for nonalcoholic fatty liver disease when the disease was quiescent, measured by magnetic resonance/endoscopy, and was unrelated to symptom severity. Nonalcoholic fatty liver disease was associated with the pleiotropic cytokine interleukin (IL)-8/CXCL8 but not with traditional proinflammatory cytokines (eg, tumor necrosis factor & alpha;, IL-1, IL-6).

Automated summary

This study found that active intestinal inflammation in patients with Crohn's disease (CD) increases the risk of nonalcoholic fatty liver disease (NAFLD). Specifically, CD patients have a higher prevalence of NAFLD during radiographically quiescent disease, independent of body mass index/visceral adipose tissue. Additionally, the cytokine interleukin-8 (IL-8) is associated with predicting NAFLD, while traditional proinflammatory cytokines are not.