Dietary therapies for adult and pediatric inflammatory bowel disease.

Diet is an environmental exposure implicated in the development of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dietary therapy is also a tool for management of these conditions. Nutrition therapy for IBD has been shown to reduce intestinal inflammation, promote healing, and alleviate symptoms, as well as improve patients' nutrition status. Although the mechanisms of action of most nutrition therapies for IBD are not well understood, the diets are theorized to eliminate triggers for gut dysbiosis and mucosal immune dysfunction associated with the typical Western diet. Exclusive enteral nutrition and the Crohn's disease exclusion diet are increasingly being used as the primary treatment modality for the induction of remission and/or maintenance therapy in children, and in some adults, with CD. Several other diets, such as the Mediterranean diet, anti-inflammatory diet for IBD, and diets excluding gluten, FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), lactose, or other compounds, may be helpful in symptom management in both CD and UC, though evidence for biochemical efficacy is limited. In this review, we discuss the role of diet components in IBD pathogenesis and examine diets currently used in the management of children and adults with IBD. We also address practical, psychosocial, and cultural considerations for dietary therapy across diverse populations.

Cost-Effectiveness Analysis of Hepatocellular Carcinoma Surveillance in Nonalcoholic Fatty Liver Disease Cirrhosis Using US Visualization Score C-Triggered Abbreviated MRI.

INTRODUCTION: Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis. METHODS: We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables. RESULTS: US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance. DISCUSSION: HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

INTRODUCTION: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy. METHODS: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52. RESULTS: Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib. DISCUSSION: Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145).

Incorporating Nutrition-Based Strategies into IBD Treatment.

PURPOSE OF REVIEW: Diet and nutrition have emerged as key factors in the development and course of inflammatory bowel disease (IBD), including the approach to therapy. We present an overview of evidence-based recommendations and recent research in dietary therapy and nutrition management for patients with IBD. RECENT FINDINGS: Patients with IBD should undergo a comprehensive nutrition assessment with the assistance of a registered dietitian (RD), including screening for micronutrient deficiencies. Multiple specialized whole foods and liquid formula diets have been evaluated as part of induction and maintenance therapy for IBD. Nutritional status should ideally be optimized in the perioperative setting as well. Nutritional issues are prevalent among IBD patients and should be addressed by a multidisciplinary team, tailored to each patient's disease type, severity and course, including response to medical therapy and need for surgical management, as well as relevant psychosocial considerations.

Cost-Effectiveness Analysis of Screening for Hepatitis B Virus Infection in Patients With Solid Tumors Before Initiating Chemotherapy.

BACKGROUND & AIMS: Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. METHODS: We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. RESULTS: The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. CONCLUSIONS: In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.

A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology.

Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.

Does Obesity Influence the Risk of Clostridium difficile Infection Among Patients with Ulcerative Colitis?

BACKGROUND: Patients with ulcerative colitis (UC) are at an increased risk of Clostridium difficile infection (CDI) compared with the general population. Recent data suggest that obesity also increases the risk of CDI. AIMS: To examine whether obesity influences the risk of CDI among patients with UC. STUDY: We conducted a retrospective cross-sectional study of UC patients seen in gastroenterology clinic between January 1, 2014, and December 31, 2015. Records were reviewed for patients with the diagnosis of UC prior to 2014, and the first diagnosis of CDI between January 1, 2014, and December 31, 2015. Using body mass index (BMI), patients were classified into underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30). Age-adjusted and multivariate logistic regression was performed including gender, tobacco use, UC disease duration, medication exposure, and vitamin D deficiency. RESULTS: Of the 636 patients with UC, 114 (18%) were obese, 232 (36%) overweight, 274 (43%) normal weight, and 16 (2.5%) underweight. Nineteen patients (3.0%) developed CDI during the study period. CDI risk was not associated with BMI (OR 0.90, 95% CI 0.79-1.02). Compared to normal weight patients, risk of CDI was not influenced by being obese (multivariate OR 0.63, 95% CI 0.15-2.58), overweight (multivariate OR 0.33, 95% CI 0.08-1.30), or underweight (multivariate OR 2.98, 95% CI 0.45-19.83). CDI was associated with ever use of TNF therapy (multivariate OR 6.09, 95% CI 2.07-17.93) but not vedolizumab (multivariate OR 0.76, 95% CI 0.08-7.36). CONCLUSIONS: Obesity does not appear to be associated with the risk of C. difficile infection among patients with UC.

Efficacy of the Autoimmune Protocol Diet for Inflammatory Bowel Disease.

INTRODUCTION: Data suggest dietary modification can improve clinical responses in inflammatory bowel disease (IBD). The goal of this study was to determine the efficacy of an autoimmune protocol diet in patients with Crohn's disease and ulcerative colitis. METHODS: We enrolled adults with active IBD (Harvey-Bradshaw index ≥ 5 or partial Mayo score ≥3 and erosions on endoscopy and/or elevated fecal calprotectin). For the autoimmune protocol, patients underwent 6-week elimination followed by 5-week maintenance phase. Clinical indices, laboratories, and biomarkers were assessed at baseline and weeks 6 and 11. Endoscopy was performed at study completion. RESULTS: The final cohort included 15 patients with IBD, with mean disease duration 19 years (SD 14.6) and active biological use in 7 (47%) patients. Nutrient repletion was initiated for deficiencies in vitamin D (n = 3) and iron (n = 6). From week 0 to weeks 6 and 11, mean partial Mayo score significantly improved from 5.8 (SD 1.2) to 1.2 (SD 2.0) and 1.0 (SD 2.0) for ulcerative colitis, and mean Harvey-Bradshaw index significantly improved from 7 (SD 1.5) to 3.6 (SD 2.1) and 3.4 (SD 2.6) for Crohn's disease. C-reactive protein did not significantly change during study. Mean fecal calprotectin improved from 471 (SD 562) to 112 (SD 104) at week 11 (P = 0.12). Among those with follow-up endoscopy at week 11 (n = 7), improvements were noted in simple endoscopic score for Crohn's disease (n = 1), Rutgeerts score (n = 1), and Mayo endoscopy subscore (n = 4). DISCUSSION: Dietary elimination can improve symptoms and endoscopic inflammation in patients with IBD. Randomized controlled trials are warranted.

Stool DNA Analysis is Cost-Effective for Colorectal Cancer Surveillance in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Patients with chronic ulcerative colitis are at increased risk for colorectal neoplasia (CRN). Surveillance by white-light endoscopy (WLE) or chromoendoscopy may reduce risk of CRN, but these strategies are underused. Analysis of DNA from stool samples (sDNA) can detect CRN with high levels of sensitivity, but it is not clear if this approach is cost-effective. We simulated these strategies for CRN detection to determine which approach is most cost-effective. METHODS: We adapted a previously published Markov model to simulate the clinical course of chronic ulcerative colitis, the incidence of cancer or dysplasia, and costs and benefits of care with 4 surveillance strategies: (1) analysis of sDNA and diagnostic chromoendoscopy for patients with positive results, (2) analysis of sDNA with diagnostic WLE for patients with positive results, (3) chromoendoscopy with targeted collection of biopsies, or (4) WLE with random collection of biopsies. Costs were based on 2014 Medicare reimbursement. The primary outcome was the incremental cost-effectiveness ratio (incremental cost/incremental difference in quality-adjusted life-years) compared with no surveillance and a willingness-to-pay threshold of $50,000. RESULTS: All strategies fell below the willingness-to-pay threshold at 2-year intervals. Incremental cost-effectiveness ratios were $16,362 per quality-adjusted life-year for sDNA analysis with diagnostic chromoendoscopy; $18,643 per quality-adjusted life-year for sDNA analysis with diagnostic WLE; $23,830 per quality-adjusted life-year for chromoendoscopy alone; and $27,907 per quality-adjusted life-year for WLE alone. In sensitivity analyses, sDNA analysis with diagnostic chromoendoscopy was more cost-effective than chromoendoscopy alone, up to a cost of $1135 per sDNA test. sDNA analysis remained cost-effective at all rates of compliance; when combined with diagnostic chromoendoscopy, this approach was preferred over chromoendoscopy alone, when the specificity of the sDNA test for CRN was >65%. CONCLUSIONS: Based on a Markov model, surveillance for CRN is cost-effective for patients with chronic ulcerative colitis. Analysis of sDNA with chromoendoscopies for patients with positive results was more cost-effective than chromoendoscopy or WLE alone.

Endogenous levels of circulating androgens and risk of Crohn's disease and ulcerative colitis among women: a nested case-control study from the nurses' health study cohorts.

BACKGROUND: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We conducted a nested case-control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. RESULTS: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08-0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). CONCLUSIONS: Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted.

Measures of obesity and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Obesity is associated with intestinal-specific inflammation. Nonetheless, a specific role of obesity in the etiology of inflammatory bowel disease is unclear. METHODS: We conducted a prospective cohort study of U.S. women enrolled in 1989 in the Nurses' Health Study II. At baseline, we collected information on height, weight, waist and hip circumference, weight at age 18, and body shape at age 20. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Among 111,498 women (median age, 35 yr), we documented 153 cases of Crohn's disease (CD) and 229 cases of ulcerative colitis (UC) more than 18 years of follow-up, encompassing 2,028,769 person-years. Compared with women with normal BMI, the multivariate-adjusted hazard ratios of CD were 2.33 (95% CI, 1.15-4.69) for obese women at age 18 and 1.58 (95% CI, 1.01-2.47) for obese women at baseline. Increasing weight gain between age 18 and baseline was associated with increased risk of CD (Ptrend = 0.04). Adolescent body habitus was also associated with risk of CD with a multivariate-adjusted hazard ratio of CD of 1.63 (95% CI, 1.07-2.50) for women with overweight/obese body shape compared with women with a thin/slender body shape. We did not observe a significant association between any of these anthropometric measures and risk of UC. CONCLUSIONS: In a large prospective cohort of U.S. women, measures of adiposity were associated with an increased risk of CD but not UC. Additional studies are needed to elucidate the biological mechanisms by which excess adiposity may increase the risk of CD.

Natural history of Crohn's disease following total colectomy and end ileostomy.

BACKGROUND: Crohn's disease (CD) requires surgical management in up to two-thirds of patients. Few studies have addressed the issue of ileal recurrence after colectomy and permanent ileostomy. The aims of our study were to assess the rate and predictors of postoperative recurrence of CD in patients with permanent ileostomy. METHODS: In a retrospective study from a tertiary referral center, we analyzed the natural history of patients with CD who underwent total colectomy and permanent ileostomy. Our primary outcomes were (1) overall disease recurrence including luminal recurrence, perianal disease or peristomal lesions requiring therapy, and (2) luminal recurrence alone defined as endoscopic and clinical recurrence within the terminal ileum. We examined if patient characteristics predicted recurrence using multivariate Cox proportional hazard models. RESULTS: Our study included 73 patients with CD followed for a mean of 28 months (range, 0-168 mo) after total colectomy and permanent ileostomy. Twenty patients had overall disease recurrence within 10 years after surgery, at rates of 15% and 50% at 1 and 5 years, respectively. Rate of luminal recurrence was 8% and 35% at 1 and 5 years, respectively. Diagnosis at age less than 18 years (hazard ratio, 2.94; 95% confidence interval, 1.14-7.62) and anti-tumor necrosis factor therapy before surgery (hazard ratio, 4.75; 95% confidence interval, 1.25-18.13) were the only independent predictive factors for overall disease recurrence. CONCLUSIONS: Up to one-third of patients with CD have overall recurrence of disease after treatment with total colectomy and permanent ileostomy. There is need to develop algorithms for surveillance and management of this select subgroup of patients.

Sleep duration affects risk for ulcerative colitis: a prospective cohort study.

BACKGROUND & AIMS: Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. METHODS: We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. CONCLUSIONS: On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.

Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

BACKGROUND: Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. METHODS: We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. RESULTS: At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. CONCLUSIONS: In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

Thromboprophylaxis is associated with reduced post-hospitalization venous thromboembolic events in patients with inflammatory bowel diseases.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE after IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. METHODS: In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn's disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person-time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE after discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days, respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22-0.97). Increased numbers of comorbidities (HR, 1.30; 95% CI, 1.16-1.47) and need for corticosteroids before hospitalization (HR, 1.71; 95% CI, 1.02-2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. CONCLUSIONS: Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE.