Disease activity in inflammatory bowel disease patients is associated with increased liver fat content and liver fibrosis during follow-up.

PURPOSE: Liver steatosis is a frequently reported condition in patients with inflammatory bowel disease (IBD). Different factors, both metabolic and IBD-associated, are believed to contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis and fibrosis in IBD patients and to evaluate which factors influence changes in steatosis and fibrosis during follow-up. METHODS: From June 2017 to February 2018, demographic and biochemical data was collected at baseline and after 6-12 months. Measured by transient elastography (FibroScan), liver steatosis was defined as Controlled Attenuation Parameter (CAP) ≥248 and fibrosis as liver stiffness value (Emed) ≥7.3 kPa. IBD disease activity was defined as C-reactive protein (CRP) ≥10 mg/l and/or fecal calprotectin (FCP) ≥150 µg/g. Univariate and multivariate regression analysis was performed; a p-value of ≤0.05 was considered significant. RESULTS: Eighty-two out of 112 patients were seen for follow-up; 56% were male. The mean age was 43 ± 16.0 years, and mean BMI was 25.1 ± 4.7 kg/m2. The prevalence of liver steatosis was 40% and of fibrosis was 20%. At baseline, 26 patients (32%) had an active episode of IBD. Using a multivariate analysis, disease activity at baseline was associated with an increase in liver steatosis (B = 37, 95% CI 4.31-69.35, p = 0.027) and liver fibrosis (B = 1.2, 95% CI 0.27-2.14, p = 0.016) during follow-up. CONCLUSIONS: This study confirms the relatively high prevalence of liver steatosis and fibrosis in IBD patients. We demonstrate that active IBD at baseline is associated with both an increase in liver steatosis and fibrosis during follow-up.

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers.

OBJECTIVE: The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion. DESIGN: Randomized, single-blind crossover design. SUBJECTS: Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4). INTERVENTION: Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment 13 g) or 9 g (treatment 19 g) fat (safflower oil). MEASUREMENTS: Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY. RESULTS: C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g 13 g and 19 g) significantly increased satiety during and after fat perfusion, without differences in satiety between 13 g and 19 g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels. CONCLUSION: Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.

Ileal brake: a sensible food target for appetite control. A review.

With the rising prevalence of obesity and related health problems increases, there is increased interest in the gastrointestinal system as a possible target for pharmacological or food-based approaches to weight management. Recent studies have shown that under normal physiological situations undigested nutrients can reach the ileum, and induce activation of the so-called "ileal brake", a combination of effects influencing digestive process and ingestive behaviour. The relevance of the ileal brake as a potential target for weight management is based on several findings: First, activation of the ileal brake has been shown to reduce food intake and increase satiety levels. Second, surgical procedures that increase exposure of the ileum to nutrients produce weight loss and improved glycaemic control. Third, the appetite-reducing effect of chronic ileal brake activation appears to be maintained over time. Together, this evidence suggests that activation of the ileal brake is an excellent long-term target to achieve sustainable reductions in food intake. This review addresses the role of the ileal brake in gut function, and considers the possible involvement of several peptide hormone mediators. Attention is given to the ability of macronutrients to activate the ileal brake, and particularly variation attributable to the physicochemical properties of fats. The emphasis is on implications of ileal brake stimulation on food intake and satiety, accompanied by evidence of effects on glycaemic control and weight loss.

Safety of Anti-TNF Treatment in Liver Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Little is known about the risk of serious infection when combining anti-tumour necrosis factor [TNF] therapy for refractory inflammatory bowel disease [IBD] with immunosuppression after liver transplantation [LT]. Our aim was to investigate the infection risk in this patient group by systematic review and meta-analysis of the available data. METHODS: A search was conducted for full papers and conference proceedings through September 2015, regarding liver transplant recipients and anti-TNF therapy. All studies were appraised using the adapted Newcastle-Ottawa Scale [NOS]. Two reviewers independently extracted patient data [age, duration of follow-up, number of all infections, number of serious infections, time since transplant]. As an additional control population, primary sclerosing cholangitis [PSC]-IBD patients from the Leiden University Medical Center [LUMC] LT cohort were used. Poisson regression was used to compare serious infections (according to International Conference on Harmonisation [ICH] definition) per patien-year follow-up between the anti-TNF and control groups. RESULTS: In all 465 articles and abstracts were identified, of which eight were included. These contained 53 post-LT patients on anti-TNF therapy and 23 post-LT patients not exposed to anti-TNF therapy. From the LUMC LT-cohort, 41 PSC patients with PSC-IBD not exposed to anti-TNF therapy were included as control population. The infection rate for TNF-exposed patients was 0.168 serious infections per patient year, compared with 0.149 in the control patients (rate ratio 1.12 [95% confidence interval: 0.233-5.404, P = 0.886]. When correcting for time since transplant, the infection rate was 0.194 in the TNF-exposed vs 0.115 in the non-exposed [p = 0.219]. CONCLUSIONS: No significant increase in the rate of serious infection was observed in LT recipients with PSC-IBD during exposure to anti-TNF therapy.