Weeks Of Exclusive Enteral Nutrition Research Articles

Inflammation-related Proteins Support Diagnosis of Inflammatory Bowel Disease andAre Modified by Exclusive Enteral Nutrition in Children With Crohn's Disease, Especially of Ileal Phenotype.

The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD. Ninety-two IRPs were quantified using Olink proteomics in children with CD (n = 53), UC (n = 11), and non-IBD (n = 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied. Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders. Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement.

S2725 Enteral Nutrition in Crohns Disease With Abscess

Introduction: Enteral nutrition has emerged as a treatment option for patients with active Crohn’s disease. We report a patient achieving remission with enteral nutrition in conjunction with ustekinumab. Case Description/Methods: A 29-year-old Caucasian male with Crohn’s disease not on therapy presented with abdominal pain, nausea and vomiting. In the past 3 years, he had multiple visits to urgent care for symptoms, each treated with systemic steroids. On presentation, he had an elevated CRP of 143.9 mg/L and MR enterography showed inflammation in the small bowel and terminal ileum. The patient completed a 7-day course of piperacillin-tazobactam and was started on ustekinumab. He was readmitted 10 days later with WBC of 16.9 10*3/ul, CRP of 305.6 mg/L, tachycardia, night sweats and worsening abdominal pain. Imaging showed continued inflammation of small bowel and terminal ileum with a mesenteric abscess connected to the D4 portion of duodenum by a fistulous tract. Piperacillin-tazobactam was started for 14 days along with 5 weeks of exclusive enteral nutrition (EEN) with BOOST, ∼2145 kcals daily. Repeat imaging showed interval decrease in abscess size and then complete resolution. Disease remission was obtained with alleviation of abdominal pain and weight gain of 5 lbs. Labs normalized with CRP < 3 mg/L, at the end of the 5 weeks of EEN. Discussion: EEN is the administration of a polymeric formula as the sole source of nutrition for a limited period (4-8 weeks). In Crohn’s disease, EEN has been shown to help reach remission in 85-90% of patients. It has special consideration in achieving remission in CD patients who have steroid intolerance or contraindications to systemic steroids. The mechanism of EEN in treatment of Crohns disease is not completely understood but is hypothesized to be multifactorial and potentially involve alterations in gut microbiota, decreasing gut permeability, and allowing restoration of epithelial barrier. Limited studies have been conducted on concomitant use of EEN with biologic agents. These studies have primarily been done looking at anti-TNF agents, such as infliximab, and sustained remission rates. Induction therapy with such agents as ustekinumab take time to have clinical effect, 56% of patients have response in 6 weeks. In this patient, initiation of ustekinumab along with EEN was successful in achievement of clinical remission and reduction in inflammatory markers.

Induction of Remission in Pediatric Crohn's Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index.

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

Modified Crohn's disease exclusion diet is equally effective as exclusive enteral nutrition: Real-world data.

Data on the efficacy of the newly established dietetic treatment of Crohn's disease (CD), the CD exclusion diet (CDED), are scarce. The aim of this study was to provide real-world data on the efficacy of CDED in comparison with exclusive enteral nutrition (EEN) for remission induction. A retrospective analysis of children diagnosed with CD who were treated with CDED + partial EN (PEN) or with EEN was performed. Eighty percent of the children assigned to CDED + PEN underwent 1-2 weeks of EEN prior to CDED + PEN. For all children, data from the medical charts were extracted before the introduction of diet therapy and at the end of EEN or CDED + PEN phase 1. A total of 61 patients (49.2% females; median age, 14.4 years [minimum: 6.7, maximum: 17.9]) were included in the study; 42 children (68.9%) achieved remission, 27 of 41 (65.9%) received EEN and 15 of 20 (75.0%) received CDED + PEN. There was no significant difference in the failure of nutrition therapy between the two groups (P = .469). Patients receiving CDED + PEN had significantly higher weight gain (P = .002) and increases in body mass index z-score (P = .001) compared with patients who received EEN alone. Treatment with CDED + PEN (with prior 1-2 weeks of EEN) has comparable efficacy to EEN therapy alone in inducing remission in children with CD, and it leads to better weight gain. Further studies are needed to confirm these results.

OP15 Cyclic exclusive enteral nutrition to maintain longterm drug-free remission in Paediatric Crohn’s Disease: The CD HOPE study of the GETAID pédiatrique

Abstract Background To address the question if pediatric CD patients responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of immunosuppressive drugs, we designed a prospective randomized trial (CD-HOPE) comparing cyclic exclusive enteral nutrition (EEN) to daily supplement over a 12 month period. Methods CD patients (6–17 years) who successfully completed at least 6 weeks of EEN with clinical remission (wPCDAI ≤12.5) were recruited in 21 sites of the French GETAID pédiatrique between 12.2014 and 09.2018. All drug therapy had to be stopped at least 4 weeks prior to inclusion. A total of 112 patients were screened with 100 patients randomized to group A cyclic EEN (100% of caloric requirement) every 8 weeks for 2 weeks or group B daily supplementary nutrition (25% of caloric requirement). Patient stratification according to age (&amp;lt; 10 years or older) and previous drug exposure or not. EEN and the nutritional supplement were in form of MODULEN IBD®. Except for the two weeks of EEN in group A food access was not restricted. Primary objective was the comparison of relapse rates at 12 months (defined as a wPCDAI &amp;gt;12.5 at two consecutive visits) between the two groups (log-rank test per protocol). Additional analyses were performed using a multivariate regression analysis and cox model. Results 49 CD patients were randomized to group A (cyclic EEN) and 51 to group B (daily supplement) with 43/49 and 44/51 newly diagnosed patients without any previous drug exposure. Baseline characteristics were comparable between the two groups. Median age was 12 and 13 years, group A and B respectively. At the final 12 months visits a total of 25/49 patients (group A) remained in remission without disease activation compared to 12/51 patients (group B) (p=0.004) with a hazard ratio of 0.48 (0.29–0.80) (p= 0.0051). Kaplan Maier survival remission rates are shown in figure 1. Mean fecal calprotectine levels showed no significant difference between the two groups (297, 399 and 469 at month 0, 3, and 12 visits in group A and 480, 606, and 283 at month 0,3, and 12 visits in group B). Mucosal healing at M12 months was achieved in 25/49 patients (group A) and 18/51 patients (group B), with a mucosal healing rate of 52% (group A) and 33% (group B). Both treatment arms showed a significant catch-up growth. Conclusion This is first trial indicating that children/adolescents with CD responding to EEN as induction therapy can be maintained on remission with a nutritional therapy without immunosuppressors/biologics. However, daily nutritional supplement with normal access to food was not successful with a relapse rate of 76%. This study was supported by an unrestricted grant from Nestlé Health Science and sponsored by APHP.

Lyophilized fecal short-chain fatty acid and electrolyte determination by capillary electrophoresis with indirect UV detection for assessment of pediatric inflammatory bowel disease

Short-chain fatty acids (SCFAs) and electrolytes are major constituents of human feces involved in maintaining gastrointestinal homeostasis that underlie complex diet, host and microbiome interactions. Reliable quantification of SCFAs and electrolytes is challenging given the heterogeneity of stool specimens from pediatric patients with diarrhea-predominate inflammatory bowel disease (IBD). Herein, we introduce two validated methods for determination of 3 SCFAs and 5 electrolytes consistently quantified from fecal extracts when using capillary electrophoresis with indirect UV detection (CE-iUV), where concentrations are normalized to total dried weight (mmol/kg d.w.). Lyophilization facilitates sample handling and extraction of heterogeneous stool specimens (∼ 15 mg) from a cohort of children with Crohn’s disease (CD, n = 12) and ulcerative colitis (UC, n = 10) treated with exclusive enteral nutrition (EEN) or corticosteroid (CS) therapy to induce remission, respectively. Good technical precision (mean CV = 13 %, n = 14) and accuracy (recovery from 84 to 116%) is demonstrated for SCFAs and electrolytes from freeze dried stool extracts using a modified Bligh-Dyer protocol with low micromolar detection limits (∼ 2–15 μM). Fecal butyrate is 2.6-fold higher in CD as compared to UC patients (effect size = 1.51; p = 0.00291), and there is a strong co-linearity between fecal butyrate and acetate (r = 0.835) unlike propionate, which is correlated with fecal calprotectin (r = 0.517), a protein biomarker of intestinal inflammation. Also, a longitudinal study of matching stool samples collected from a sub-set of IBD patients revealed about a 7-fold enrichment in magnesium and calcium following 4 weeks of EEN as compared to baseline (F > 4.1 ; p < 0.05) unlike the CS treatment arm with no changes in other fecal SCFAs and electrolytes, including sodium, potassium, and ammonium. CE-iUV enables rapid fecal SCFA and electrolyte determination as required for new insights into the role of gut dysbiosis in IBD, as well as treatment monitoring of nutritional interventions that stabilize the disease course in affected children.

Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn's disease: the Indian experience.

Background/AimsExclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn’s disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD.MethodsThis is a retrospective analysis of adults with moderate to severe active (Crohn’s Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points.ResultsOut of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P<0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively).ConclusionsEEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required.

P455 Adherence to enteral nutrition therapy by adults with active Crohn’s disease is associated with conscientiousness personality trait

Abstract Background Conscientiousness is a personality trait characterised by the ability to control impulses, delay gratification, set and reach goals, and plan in advance. Conscientious people are more likely to be non-smokers, do physical activity and practice healthy eating behaviours. They are also more likely to be adherent to medication. The aim of this study was to assess whether people with Crohn’s disease who score high on conscientiousness are more likely to be adherent to enteral nutrition (EN) therapy than low scorers. Methods Adults aged 16 to 40 years with newly diagnosed Crohn’s disease or having a flare of disease were invited by their gastroenterologist to use nutrition therapy to induce disease remission. Nutrition therapy was either eight weeks of exclusive enteral nutrition (EN) or two weeks of exclusive EN followed by six weeks of partial EN and one meal per day. A convenience control group of healthy participants with no history of gastrointestinal symptoms was also recruited to use exclusive EN for two weeks. Adherence to EN was self-reported fortnightly using a standardised questionnaire. Non-adherence was defined as patients who repeatedly ate foods while using EN or ate more than one meal per day on partial EN. Patients who could not initiate or did not tolerate the EN formula were included in the non-adherent group. Prior to starting nutrition therapy, conscientiousness was measured using the well-validated conscientiousness subset of the Big Five Inventory. Results Twenty-three (59%) of the 39 patients recruited with Crohn’s disease completed and adhered to the eight-week treatment. Reasons for non-adherence by the 14 patients who did not complete treatment included: could not initiate EN (n = 4), non-response at week 4 (n = 2), intolerance of EN (n = 7) or repeated eating of food or started eating food again prior to the end of treatment (n = 2). Seventeen (81%) of the 21 healthy controls completed and adhered to 2 weeks of exclusive EN. Reasons for non-adherence were could not initiate EN (n = 3) or intolerance of the formula (n = 1). Adherence and completion of EN therapy were associated with a greater mean conscientiousness score 35.57 (95% CI: 32.88, 38.25) compared with the non-adherence group mean 30.13 (95% CI: 26.53, 33.73), p = 0.014. Mean conscientiousness score of the healthy controls who completed exclusive EN was similar to the Crohn’s disease group (36.65 (95% CI: 33.53, 39.77), p &amp;gt; 0.05). Conclusion Conscientiousness was associated with adherence to EN therapy. EN therapy can be a cognitively and emotionally demanding treatment and this personality trait should ideally be considered when determining suitable candidates for EN therapy.

P547 Inadequate vitamin C status and association with inflammatory biomarkers in adults with active Crohn’s disease

Abstract Background Micronutrient deficiencies are common in inflammatory bowel disease (IBD) due to the inflammatory burden and changes in dietary intake. Vitamin C, an essential water-soluble antioxidant required for tissue repair and immune function, is found primarily in fresh fruit and vegetables however, this food group is more often avoided by people with IBD compared with the general population. This research aimed to determine serum vitamin C status in subjects with active Crohn’s disease, measure urinary vitamin C excretion in healthy controls (HC) and Crohn’s disease patients before and after exclusive enteral nutrition (EEN) and assess associations between inflammatory markers and vitamin C. Methods Stored serum and random urine samples prospectively collected from adults with mild to moderately active Crohn’s disease and adult HC were analysed. Both HC and Crohn’s disease groups received EEN with a known vitamin C content for two weeks. Serum and urinary vitamin C were measured using high-performance liquid chromatography with electrochemical detection. Urinary vitamin C was standardised to urinary creatinine. Non-parametric t-tests and correlations were performed. Results EEN was initiated in 38 patients (aged 16 to 39 years old). Inadequate serum vitamin C (&amp;lt;50 µmol/l) was present in 36/38 patients with active Crohn’s disease and 45% had hypovitaminosis C. Baseline C-reactive protein (CRP) was 12 mg/l (range, 3 to 158 mg/l) and faecal calprotectin was 1065 µg/g (range, 60 to 3838 µg/g). Serum vitamin C correlated weakly with CRP (r = −0.30 95% CI: −0.58 to 0.03, p = 0.06) but not with faecal calprotectin. Two weeks of EEN was completed by 30 (79%) patients and 17 (81%) HC. The average vitamin C intake was 168mg/day (range, 108–252 mg/day). Baseline urinary excretion of vitamin C was low in both Crohn’s disease and HC. Following EEN urinary vitamin C excretion increased significantly in both groups (Figure 1). Conclusion Patients with active Crohn’s disease had inadequate vitamin C status. EEN increased urinary vitamin C excretion in both Crohn’s disease and HC, suggesting low baseline dietary vitamin C intake and potentially enhanced utilisation. Further research with a larger patient cohort would provide a greater understanding of vitamin C metabolism in active Crohn’s disease.

Benefits of Exclusive Enteral Nutrition in Adults With Complex Active Crohn’s Disease: A Case Series of 13 Consecutive Patients

Abstract Background and Aims Immunosuppressive therapy is routine for adults with complex active Crohn’s disease (CD), however carries risks, particularly in the setting of sepsis. Exclusive enteral nutrition (EEN) is widely used in paediatric CD, yet efficacy data in adults are sparse. This study evaluated outcomes of EEN in adults with complex active CD. Methods Between December 2016 and June 2018, 13 patients with complex active CD (range 20–74 years) managed at a single hospital received 2 or more weeks of EEN. Patients were offered EEN based on either malnutrition, contraindication to immunosuppression, or CD refractory to multiple therapies. Subjective and objective outcomes were recorded at 2 and 6 weeks and compared with baseline data. Results Nine of 13 patients experienced subjective improvement in wellbeing. Objective improvements included nine CRP decrements (median = 87.7 mg/L, IQR = 70.6 mg/L), nine serum albumin increments (median = 7 g/L, IQR = 4 g/L), and six gained weight (median = 3.6 kg, IQR = 3.0 kg). All five patients with complex abscess resolved without surgery. One ileocolic fistula and one enterocutaneous fistula achieved resolution without surgery. One of two perianal fistulae cases resolved without surgery. Seven of 10 patients initially thought to need surgery avoided it due to disease resolution. Only one of the three patients who proceeded to surgery sustained a post-operative complication. There were no EEN-associated complications. Conclusions In complex active CD, our real-world data show that EEN improves wellbeing, decreases inflammatory markers, leads to healthy weight gain, reduces need for surgical intervention, and reduces postoperative complications.

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction.

SummaryBackgroundFaecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re‐introduction and the influence of maintenance enteral nutrition.AimsTo study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition.MethodsChildren with Crohn's disease were followed during exclusive enteral nutrition and during food‐reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food‐reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3.ResultsSixty‐six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non‐users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: −0.573, P = .041), kcals (rho: −0.584, P = .036) and % energy intake (rho: −0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission.ConclusionsThe effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.

Exclusive Enteral Nutrition: Clinical Effects and Changes in Mucosal Cytokine Profile in Pediatric New Inflammatory Bowel Disease.

Exclusive Enteral Nutrition (EEN) is the first-line treatment in children with Crohn’s disease (CD) for induction of remission. However, the mode of action remains conjectural. The aim of this study was to investigate whether the effect of EEN is paralleled by changes in the mucosal cytokine profiles (MCP). Twelve children with new onset inflammatory bowel disease (IBD) received induction treatment with a polymeric EEN. We assessed clinical, endoscopic and histologic scoring before and after EEN. Twelve colonic cytokines were analyzed by Polymerase Chain Reaction (PCR) in six of the IBD patients at onset and after EEN as well as in six non-IBD control children at the diagnostic colonoscopy. Twelve children completed 6 weeks of EEN, except from one child who completed 4 weeks. At the control colonoscopy, 83% were in complete clinical remission. Changes were found in the MCPs of individual patients after EEN. In particular, children with IBD showed significantly higher values of Interleukin (IL)-12β (p = 0.008) and IL-23α (p = 0.02) compared to non-IBD controls at the diagnostic colonoscopy. Furthermore, an overall change in proinflammatory cytokines was noted in the IBD-group after treatment. Further studies are warranted to understand the role of EEN in MCP.

Newly Diagnosed Crohn’s Disease Treated with Standard Care or Enteral Nutrition: Psychological Outcomes over 6 Months

Background and Aim: Impaired health-related quality of life and higher rates of anxiety and depression are observed in patients with Crohn’s disease. This single center study aimed to describe and compare longitudinal psychological outcomes of newly diagnosed Crohn’s disease patients treated with standard care or enteral nutrition to induce remission. Methods:Two separate cohorts of patients were recruited from one center and treated with standard care (n = 22) or enteral nutrition (n = 18) to induce disease remission. Disease activity, quality of life, anxiety, and depression were ­assessed at diagnosis and month 6. Results:At baseline, quality of life (n = 40) was not correlated with disease activity; symptoms of anxiety and depression were present in 15 (38%) and 5 (13%) of the 40 patients, respectively. Significant improvements in quality of life (p <0.0001) and anxiety scores (p = 0.002) were observed after 2 weeks of exclusive enteral nutrition, and at month 6 significant improvements in all psychological outcomes were observed. At month 6, patients who received standard care had a significant improvement in quality of life (p = 0.004), but not in anxiety or depression scores, and there were no differences in psychological outcomes between the treatment groups. Overall, 34/40 (85%) patients were in clinical remission at month 6, and a clinically significant quality of life score was achieved by 31/40 (78%). Conclusions:Patient health-related quality of life and symptoms of anxiety and depression improved as disease activity improved, and 6 months after diagnosis psychological outcomes were similar in patients treated with standard care or enteral nutrition to initially induce remission.

Efficacy of exclusive enteral nutrition in complicated Crohn’s disease

Aim: To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn’s disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture.Method: Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287).Results: Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18–60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohn's disease activity index significantly decreased (223.43 ± 65.5 vs. 106.77 ± 42.73, p ≤ .001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p ≤ .01), nutritional parameters increased (p ≤ .01) and the European Nutritional Risk Screening (2002) decreased (p ≤ .01).Conclusion: EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.

Treatment of Active Crohn’s Disease with Exclusive and Partial Enteral Nutrition: A Pilot Study in Adults

Background and Aim: Enteral nutrition (EN) is not commonly used for the treatment of adults with active Crohn’s disease (CD), despite patient interest in nutrition-based alternatives to corticosteroids and evidence of efficacy in paediatric CD. The aim of this study was to assess the impact of 2 different EN regimens on disease symptoms, nutrition and inflammatory markers in young adults with active CD. Methods: A prospective non-randomized pilot study of adults aged 16–40 years with active CD on endoscopy or imaging was undertaken. Patients were sequentially recruited to use 2 weeks of exclusive EN (EEN) followed by either 6 weeks of EEN or partial EN (PEN) with usual diet. Assessments of disease symptoms, nutrition and inflammatory markers were undertaken at baseline and throughout the treatment. Results: Thirty-eight patients with active disease were recruited. Thirty-two (84%) patients completed 2 weeks of EEN and had significant improvements in disease symptoms (p = 0.003), serum c-reactive protein (CRP; p = 0.005), insulin-like growth factor-1 (p = 0.006) and faecal calprotectin (FC; p = 0.028). During the following 6 weeks, 21 patients continued EEN (14 [67%] completed treatment) and 11 patients used PEN (9 [82%] completed treatment). Initial improvements in symptoms, CRP and nutrition markers were sustained over the next 6 weeks on both treatments. FC non-significantly increased in 5 out of 9 patients who used PEN and at week 8 FC was greater than 500 µg/g in 9 out of 14 and 7 out of 9 patients who used exclusive or PEN respectively. There was no significant difference in clinical outcomes between the 2 groups at week 8. Conclusion: Two weeks of EEN significantly improved disease symptoms, nutrition and inflammatory markers. Further treatment with exclusive or PEN maintained initial improvements.

The role of exclusive enteral nutrition in the management of orofacial granulomatosis in children

Orofacial granulomatosis (OFG) is a term used to describe a persistent, painless swelling of lips and orofacial region. It can be associated with ulceration, gingival hypertrophy and cobble stone appearance of the buccal mucosa. OFG is commonly associated with Crohn's disease and can precede the intestinal manifestation of the disease. Exclusive enteral nutrition (EEN) is a recognized treatment for induction of remission for Crohn's disease. The aim of this study was to review the use of EEN in the management of OFG in children. Retrospective review of medical records of all children diagnosed with OFG between 2007 and 2012 was conducted. Presence of comorbidities, progression to inflammatory bowel disease (IBD) and response to EEN was evaluated. Twenty-nine children were included, mean age at diagnosis was 9 years (standard deviation 3.9) years. Ten children had isolated OFG and 19 had OFG and IBD, of which 12 presented with OFG and IBD and 7 developed IBD later. Median time to progression to IBD was 33 months (inter quartile range: 9.8-85.5). Twenty-two children completed 6 weeks of EEN, and 19 showed clinical improvement in the OFG appearance. EEN appears to be an effective treatment option for children with isolated OFG or OFG and IBD.

Standard versus rapid food reintroduction after exclusive enteral nutritional therapy in paediatric Crohn’s disease

In paediatric Crohn's disease (PCD), 6-8 weeks of exclusive enteral nutrition (EEN) is effective in 60-80% cases. EEN is followed by gradual food reintroduction over variable (1-5 weeks) periods. Currently, there is no recommended duration or method for food reintroduction. The rationale for slow reintroduction is unclear and may be because of concerns about food intolerance or to maintain longer remission. The aims of this study were as follows: to compare relapse rates following standard and rapid reintroduction of food after EEN in PCD and to determine the duration of maintained remission in two groups of PCD patients. Two groups with PCD were compared: group A received standard food reintroduction over 5 weeks and group B received rapid reintroduction over 3 days. Data were collected over two consecutive time periods: group A (2005-2009) and group B (2009-2011). Only patients with a new diagnosis of PCD were included. Those with strictures and those on steroids or biologicals during EEN were excluded. The minimum duration of follow-up was 1 year. Group A included 20 patients and group B included 19 patients. In these groups, EEN led to clinical remission in 80% of the patients in group A and in 76% of the patients in group B. At 6 months, one-third of the patients from each group had developed relapse and a year after EEN, 50% of the patients in group A and 47% of the patients in group B developed relapse. Time to first relapse was 188 days (group A) and 136 days (group B). None of these results were statistically significant. In PCD, rapid food reintroduction following 6-week EEN is safe and equally effective as longer food reintroduction. We propose that a rapid food reintroduction schedule be recommended as the most tolerable approach for food reintroduction. Relapse rate and duration of remission are uninfluenced by the type of food reintroduction.

Clinical progress in the two years following a course of exclusive enteral nutrition in 109 paediatric patients with Crohn's disease

Exclusive enteral nutrition (EEN) is an effective first line treatment for active paediatric Crohn's disease (CD). To examine the effect of EEN on short- and long-term clinical outcome together with anthropometric measurements. Retrospective case-note review in newly diagnosed CD (<16 years) who completed 8 weeks of EEN. Demographics, anthropometry, disease characteristics and inflammatory markers were collected at EEN initiation and at 1, 2, 6, 12 & 24 months post treatment initiation. EEN response was determined by a patient global assessment. One hundred and nine patients were included (Males 68; Median age: 11.2 years). After 8 weeks EEN, 65 were in remission, 32 improved and 12 had no improvement. By 4 weeks, mean weight/BMI z-score (s.d.) increased (P < 0.02) and between 4 and 8 weeks (P < 0.05). Baseline inflammatory markers all improved significantly by week 4 (albumin, CRP and platelets; all P < 0.01) and ESR (P < 0.00001). 63/109(58%) relapsed during follow-up. 44/63(70%) patients completed a second course of EEN with similar response rate, but lower weight gain (3.3 vs. 5.1 kg, P < 0.05). Height z-score did not change significantly over the 24 months. Introduction of azathioprine within 6 months of diagnosis did not improve height outcomes at 24 months. Weight and BMI z-score improved with EEN and changes are sustained to 2 years, but height z-score did not. Seventy per cent of patients who relapsed during 2-year follow-up managed a 2nd course of EEN. The optimal therapeutic strategies for length of EEN course and to improve linear growth are awaited.

Transient Hypertransaminasemia in Pediatric Patients With Crohn Disease

To the Editor: We note with interest the article published by Schatorjé and Hoekstra (1) describing transient elevation of transaminases in 11 children with newly diagnosed Crohn disease (CD) managed with exclusive enteral nutrition (EEN) as sole therapy to induce remission. The mean levels of alanine and aspartate aminotransferases (ALT and AST) increased around 10-fold within 3 weeks of starting EEN, with subsequent normalization within 12 weeks of diagnosis. We reviewed the results of laboratory testing available for a published cohort of 12 children with newly diagnosed CD managed with 8 weeks of EEN (2). ALT and AST levels along with gamma-glutamyl transpeptidase (GGT) levels were available at diagnosis, after 2 to 3 weeks and 8 weeks of EEN as well as 1 to 2 months following EEN. Normal ranges of AST and ALT in our local laboratory were <45 and <45 U/L, respectively. At diagnosis, all of the markers were within normal ranges: mean levels of AST and ALT were 16.6 and 13.1 U/L, respectively. After 2 to 3 weeks of EEN, the average AST levels were 26.2. Subsequent means were 25 at 8 weeks and 16.8 after EEN. Average ALT levels rose initially to 21.9 U/L and were subsequently 21.2 at 8 weeks and 14.2 after EEN. ALT levels were above the upper range of normal (45 U/L) at 2 to 3 weeks in only 2 children (51 and 48, respectively) and at 8 weeks in 1 child (48 U/L). GGT levels did not change and none of the group has subsequently developed liver disease. In summary, although this retrospective data showed increasing transaminases during nutritional therapy, only a minority were above the normal range. These changes do not appear clinically significant and differ from the data provided by Schatorjé and Hoekstra (1). Further prospective investigation of transaminases during treatment of active CD will be required to establish the relevance of these observations.

Serum Concentrations of VEGF and TGF‐β1 During Exclusive Enteral Nutrition in IBD

Exclusive enteral nutrition (EEN) is an effective method of treatment in achieving remission in inflammatory bowel disease (IBD); however, its mechanism of action is still poorly understood. The objective of our study was to assess the influence of EEN on serum vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1) in children and adolescents with IBD. Thirty-nine children and adolescents with IBD (24 with Crohn disease [CD] and 15 with ulcerative colitis [UC]) and 25 healthy controls were enrolled in the study. VEGF and TGF-β1 were assessed at the baseline and after 2 and 4 weeks of EEN in CD and UC groups and once in controls using enzyme-linked immunosorbent assay immunoassays. At the baseline, we found increased serum VEGF in the CD versus UC group and controls (P < 0.05) and serum TGF-β1 in the UC versus CD group and controls (P < 0.05). During EEN, VEGF decreased in the UC and CD groups, whereas TGF-β1 increased in the CD group and decreased in the UC group. The CD group achieved disease remission faster than the UC group, and the weight gain of patients with CD during EEN was higher compared with patients with UC. Additionally, TGF-β1 concentration correlated with protein and energies daily intake in the CD group (R = 0.95; P < 0.05). Different effectiveness of EEN in achieving remission in CD and UC may result from a modification of growth factor production. EEN stimulated TGF-β1 production in CD but not in UC, which possibly resulted in higher effectiveness of EEN in this group of patients.