Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

Abstract

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. Methods A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006–2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. Results With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants’ circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. Conclusions Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.

Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease

“…Some studies suggest that IBD-induced NAFLD can further aggravate the severity of IBD and increase the risk of hepatocellular carcinoma (HCC) ( 32 – 34 ). An epidemiology study found that people with metabolic dysfunction associated fatty liver (MAFLD) have a 12% increased risk of IBD ( 35 ). Metabolic syndrome, characterized by metabolic disorders, plays a major role in this ( 36 ), with IL-17 a key factor in the clinical manifestations of metabolic syndrome ( 37 ).…”

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study

“…A low serum SHBG level has been observed as an inflammatory marker ( 53 ), suggesting a protective role of SHBG in metabolic and inflammatory diseases. Metabolic dysregulation has been implicated in the pathogenesis of IBD ( 54 ), with patients with metabolic dysfunction-associated fatty liver disease having a higher risk of developing CD ( 55 ). These findings supported the protective role of SHBG that we have identified in the development of CD.…”

Dipeptidyl peptidase‐4 inhibitor and sodium‐glucose cotransporter 2 inhibitor additively ameliorate hepatic steatosis through different mechanisms of action in high‐fat diet‐fed mice

“…4 Hepatic steatosis is also associated with the development of cardiovascular events, and previous cohort studies have shown that the incidence of cardiovascular events increases with the development of liver fibrosis. 5,6 Risk factors for hepatic steatosis include type 2 diabetes, obesity and ageing. While there are no US Food and Drug Administration-approved oral glucose-lowering drugs for hepatic steatosis, pioglitazone, 7 glucagon-like peptide-1 (GLP-1) receptor agonists 8,9 and sodium glucose cotransporter 2 (SGLT2) inhibitors 10 have been reported to improve hepatic steatosis in clinical studies.…”

“…The progression of MASLD to metabolic steatohepatitis (MASH) increases the risk of liver‐related mortality because of fibrosis of the liver 4 . Hepatic steatosis is also associated with the development of cardiovascular events, and previous cohort studies have shown that the incidence of cardiovascular events increases with the development of liver fibrosis 5,6 . Risk factors for hepatic steatosis include type 2 diabetes, obesity and ageing.…”