Frailty screening associates with hospitalization and decline in quality of life and functional status in older patients with inflammatory bowel disease.

BACKGROUND AND AIMS: To study frailty screening in association with hospitalization and decline in quality of life (QoL) and functional status in older patients with Inflammatory Bowel Diseases (IBD). METHODS: A prospective multicentre cohort study in IBD patients ≥65 years using frailty screening (G8 Questionnaire). Outcomes were all-cause, acute and IBD-related hospitalization, any infection, any malignancy, QoL (EQ5D-3L) and functional decline (Instrumental Activities of Daily Living, (IADL)) during 18 months follow-up. Confounders: age, IBD type, biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g), comorbidity (Charlson Comorbidity Index). RESULTS: Out of 405 patients, median age 70 years, 196 (48%) screened at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients (23.7%), acute hospitalizations 103 times in 74 (18.3%). Risk of frailty did not associate with all-cause (aHR 1.5, 95% CI 0.9-2.4), but did associate with acute hospitalizations (aHR 2.2, 95% CI 1.3-3.8). Infections occurred in 86 patients (21.2%) and were not associated with frailty. Decline in QoL was experienced by 108 (30.6%) patients, decline in functional status by 46 (13.3%). Frailty screening associated with decline in QoL (aOR 2.1, 95% CI 1.3-3.6) and functional status (aOR 3.7, 95% CI 1.7-8.1). CONCLUSIONS: Frailty screening associates with worse health outcomes in older patients with IBD. Further studies are needed to assess feasibility and effectiveness of implementation in routine care.

Smoking and colorectal neoplasia in patients with inflammatory bowel disease: Dose-effect relationship.

BACKGROUND AND AIMS: Prior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the association between smoking, including possible dose-effects, and the development of colorectal neoplasia in patients with inflammatory bowel disease (IBD). METHODS: We performed a prospective multicenter cohort study including patients with colonic IBD enrolled in a surveillance program in four academic hospitals between 2011 and 2021. The effects of smoking status and pack-years at study entry on subsequent recurrent events of CRN (including indefinite, low- and high-grade dysplasia, and colorectal cancer [CRC]) were evaluated using uni- and multivariable Prentice, Williams, and Peterson total-time Cox proportional hazard models. Adjustment was performed for extensive disease, prior/index dysplasia, sex, age, first-degree relative with CRC, primary sclerosing cholangitis, and endoscopic inflammation. RESULTS: In 501 of the enrolled 576 patients, at least one follow-up surveillance was performed after the study index (median follow-up 5 years). CRN occurred at least once in 105 patients. Ever smoking was not associated with recurrent CRN risk (adjusted hazard ratio [aHR] 1.04, 95% confidence interval [CI] 0.75-1.44), but an increasing number of pack-years was associated with an increased risk of recurrent CRN (aHR per 10 pack-years 1.17, 95% CI 1.03-1.32; p < 0.05). Separate analyses per IBD type did not reveal differences. CONCLUSIONS: This study found that an increase in pack-years is associated with a higher risk of recurrent CRN in patients with IBD, independent of established CRN risk factors (NCT01464151).

Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn's Disease.

OBJECTIVE: It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn's disease (CD) patients. We assessed the exposure-response relationship of UST trough concentrations with biochemical outcomes at week 24 in a prospective, real-world setting. METHODS: We performed a prospective study in patients with CD starting UST in four academic centres in the Netherlands. All patients received a weight-adjusted intravenous (IV) UST induction dose, followed by one subcutaneous (SC) dose of 90 mg UST at 8 weeks. Maintenance therapy consisted of 90 mg subcutaneous UST every 8 or 12 weeks. Individual UST concentration time course during treatment were estimated using a population pharmacokinetic (PK) model. Quartile analysis and logistic regression were performed to analyse if UST concentrations at week 8 were associated with biochemical remission rates at week 24 (C-reactive protein (CRP) ≤ 5 mg/L and / or faecal calprotectin (FC) ≤ 250 mg/kg). RESULTS: In total, 124 patients with CD were included. Patients achieving biochemical remission at week 12 and 24 had significantly higher UST levels at week 8 compared to patients without biochemical remission (6.6 µg/mL versus 3.9 µg/mL, P < 0.01 and 6.3 µg/mL versus 3.9 µg/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (≥ 6.3 µg/mL at week 8) had higher biochemical remission rates at week 12 and week 24. There was no association between UST levels at and corticosteroid-free clinical remission rates. CONCLUSION: In this real-world cohort of patients with CD, UST levels in the highest quartile (≥ 6.3 µg/mL) at week 8 were associated with higher biochemical remission rates at week 24.

Prophylactic Medication for the Prevention of Endoscopic Recurrence in Crohn's Disease: a Prospective Study Based on Clinical Risk Stratification.

BACKGROUND: To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. METHODS: In this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. RESULTS: In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. CONCLUSION: Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed.

Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease.

Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life). METHODS: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2-3 moderate deficits and 4-5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score >2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed. RESULTS: Somatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284-3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936-5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life. CONCLUSION: Deficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.

Ustekinuma b for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study.

AIMS: Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn's disease [CD]. METHODS: Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 µg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104. RESULTS: In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed. CONCLUSION: After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study.

BACKGROUND: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). AIMS: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. METHODS: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. RESULTS: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. CONCLUSIONS: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients.

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events.

PURPOSE: To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. METHODS: Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. RESULTS: In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. CONCLUSION: Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

Long-term Evaluation of Allogeneic Bone Marrow-derived Mesenchymal Stromal Cell Therapy for Crohn's Disease Perianal Fistulas.

BACKGROUND AND AIMS: The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn's disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas. METHODS: A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn's disease was performed at the Leiden University Medical Center in 2012-2014. All patients treated with bmMSCs [1 x 107 bmMSCs cohort 1, n = 5; 3 × 107 bmMSCs cohort 2, n = 5; 9 × 107 bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy. RESULTS: Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years. CONCLUSIONS: Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years.

Towards a Food Pharmacy: Immunologic Modulation through Diet.

Patients frequently wonder whether their dietary pattern influences the course of inflammatory bowel disease (IBD). Many patients even avoid certain foods that aggravate their symptoms. Although interest in nutritional interventions is rising among physicians, the current application of nutritional interventions in the IBD population is limited due to the lack of scientific evidence from clinical trials. Several studies, however, have identified associations between diet, gut microbiota, intestinal epithelial integrity, and mucosal immune responses. In patients consuming predominantly a Western diet high in n-6 poly-unsaturated fatty acids (PUFAs), sugars, and meat, and low in fruits and vegetables, an impaired gut epithelial barrier and disturbances in the intestinal microbiota have been observed, resulting in a chronic mucosal inflammation. An anti-inflammatory diet may restore this disbalance. In this review, we discuss the effects of diet on the composition of the microbiota, the gut epithelial barrier function, and the mucosal immune system.

Systematic Review: Components of a Comprehensive Geriatric Assessment in Inflammatory Bowel Disease-A Potentially Promising but Often Neglected Risk Stratification.

BACKGROUND: The population of older patients with inflammatory bowel disease [IBD] is increasing. Patient age does not fully account for poor outcomes and its clinical utility for risk stratification is limited. Comprehensive geriatric assessment [CGA], comprising a somatic, functional, mental, and social assessment or frailty, could be a predictor tool. AIMS: To systematically review literature on the kind of components of a CGA being used in adult IBD patients and the association of these components with adverse health outcomes. METHODS: An electronic literature search was performed on January 16, 2018, using PubMed, Embase, Web of Science, the Cochrane Library, CENTRAL, Emcare, and PsycINFO. Longitudinal studies relating somatic, functional, mental, and social assessment or frailty to adverse health outcomes during follow-up in IBD patients were included. The Newcastle-Ottawa scale was used to assess individual study quality. RESULTS: Of 4080 identified citations, 27 studies were included, reporting 169 associations. Median sample size was 108 patients (interquartile range [IQR] 60-704). No studies performed subgroup analyses on older patients, and the highest mean age reported was 52.7 years. Somatic and functional assessments were used in three studies, mental in 24, and social in five. No study assessed cognitive status, functional performance, or frailty. In 62 associations [36.7%], components of a CGA were significantly associated with adverse health outcome measurements. CONCLUSIONS: Components of a CGA were associated with adverse health outcomes in IBD patients, but older patients were under-represented. More studies among older patients with IBD are warranted to further establish the clinical impact of a CGA.

Systematic review with meta-analysis: risk factors for recurrent primary sclerosing cholangitis after liver transplantation.

BACKGROUND: After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC). AIM: To define risk factors for rPSC. METHODS: We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018. Studies addressing risk factors for developing rPSC were eligible for inclusion. A random effects meta-analysis was conducted using hazard ratios (HR) as effect measure. Study quality was evaluated with the Newcastle Ottawa scale. Statistical analysis was performed using Cochrane Review Manager. RESULTS: The electronic database search yielded 449 results. Twenty-one retrospective cohort studies met the inclusion criteria for the review; 14 were included in the meta-analysis. The final cohort included 2159 patients (age range 31-49 years, 68.8% male), of whom 17.7% developed rPSC. Colectomy before liver transplantation, HR 0.65 (95% CI: 0.42-0.99), cholangiocarcinoma before liver transplantation, HR 2.42 (95% CI: 1.20-4.86), inflammatory bowel disease, HR 1.73 (95% CI: 1.17-2.54), donor age, HR 1.24 (95% CI 1.0-1.45) per ten years, MELD score, HR 1.05 (95% CI: 1.02-1.08) per point and acute cellular rejection, HR of 1.94 (95% CI: 1.32-2.83) were associated with the risk of rPSC. CONCLUSIONS: Multiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC.

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease.

PURPOSE: The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank. PARTICIPANTS: Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected. FINDINGS TO DATE: As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn's disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies. FUTURE PLANS: The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app.

The effect of lipid droplet size on satiety and peptide secretion is intestinal site-specific.

BACKGROUND & AIMS: : Infusion of fat into the small intestine induces satiety. Reducing fat droplet size accelerates fat digestion, but the effect on satiety after ileal fat infusion is not known. The aim of the study was to compare the effects of fat emulsions differing in droplet size (fine, coarse) infused in either duodenum or ileum on satiety, gastric emptying and peptide secretion. METHODS: In a randomized single-blind crossover study 15 healthy volunteers received, after intubation with a nasoileal tube, 4 different treatments on 4 consecutive days. After consumption of a liquid meal, 6 g of fine or coarse fat emulsion was infused into duodenum or ileum. Study parameters were satiety, gastric emptying and gut peptides. These parameters were statistically evaluated using ANCOVA. RESULTS: In the duodenum, Fine emulsion significantly reduced hunger, increased fullness, delayed gastric emptying, but did not affect peptide secretion versus Coarse. In the ileum, Fine emulsion did not affect hunger, fullness, or gastric emptying, but significantly increased peptide secretion versus Coarse. CONCLUSIONS: Compared to larger fat droplets, smaller droplets significantly affect satiety, gastric emptying and gut peptide release, but with the effect being dependent on the intestinal location of fat delivery. DUTCH TRIALREGISTER: NTR1515.

Length and site of the small intestine exposed to fat influences hunger and food intake.

The site of intestinal fat delivery affects satiety and may affect food intake in humans. Animal data suggest that the length of the small intestine exposed to fat is also relevant. The aim of the present study was to investigate whether increasing the areas of intestinal fat exposure and the way it is exposed would affect satiety parameters and food intake. In the present single-blind, randomised, cross-over study, fifteen volunteers, each intubated with a naso-ileal tube, received four treatments on consecutive days. The oral control (control treatment) was a liquid meal (LM) containing 6 g fat ingested at t = 0 min, with saline infusion at t = 30-120 min. Experimental treatments were a fat-free LM at t = 0 min, with either 6 g oil delivered sequentially (2 g duodenal, t = 30-60 min; 2 g jejunal, t = 60-90 min; 2 g ileal, t = 90-120 min), simultaneously (2 g each to all sites, t = 30-120 min) or ileal only (6 g ileal, t = 30-120 min). Satiety parameters (hunger and fullness) and cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured until t = 180 min, when ad libitum food intake was assessed. Only the ileum treatment reduced food intake significantly over the control treatment. The ileum and simultaneous treatments significantly reduced hunger compared with the control treatment. Compared with control, no differences were observed for PYY, CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had the most pronounced effect on food intake and satiety. Increasing the areas of intestinal fat exposure only affected hunger when fat was delivered simultaneously, not sequentially, to the exposed areas. These results demonstrate that ileal brake activation offers an interesting target for the regulation of ingestive behaviour.