Showing papers in "Alimentary Pharmacology & Therapeutics in 2017"

Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.

Abstract: SummaryBackground Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use. Aim To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation. Methods A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data. Results Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. Conclusion Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.

Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease

Abstract: SummaryBackground Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. Aim To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. Methods MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. Conclusions VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis.

Abstract: SummaryBackground Abdominal ultrasound fails to detect over one-fourth of hepatocellular carcinoma (HCC) at an early stage in patients with cirrhosis. Identifying patients in whom ultrasound is of inadequate quality can inform interventions to improve surveillance effectiveness. Aim To evaluate and identify predictors of ultrasound quality in patients with cirrhosis. Methods We performed a retrospective cohort study among patients who underwent ultrasound examination for a cirrhosis-related indication between April 2015 and October 2015. Three fellowship-trained abdominal radiologists collectively reviewed all ultrasound exams and categorised exam quality as definitely adequate, likely adequate, likely inadequate and definitely inadequate to exclude liver lesions. We performed multivariable logistic regression to determine characteristics associated with inadequate ultrasound quality. Results Among 941 patients, 191 (20.3%) ultrasounds were inadequate for excluding HCC- 134 definitely inadequate and 57 likely inadequate. In multivariable analysis, inadequate quality was associated with male gender (OR 1.68, 95% CI 1.14–2.48), body mass index category (OR 1.67, 95% CI 1.45–1.93), Child–Pugh B or C cirrhosis (OR 1.93, 95% CI 1.32–2.81), alcohol-related cirrhosis (OR 2.11, 95% CI 1.33–3.37), NASH cirrhosis (OR 2.87, 95% CI 1.71–4.80), and in-patient status (OR 1.55, 95% CI 1.01–2.37). Ultrasounds were inadequate in over one-third of patients with Child–Pugh C cirrhosis, BMI >35, or NASH cirrhosis. Conclusions One in five ultrasounds in patients with cirrhosis are inadequate for exclusion of HCC, which can contribute to surveillance failure. Alternative surveillance modalities are needed in subgroups prone to inadequate ultrasounds including obese patients, those with Child Pugh B or C cirrhosis, and those with alcohol- or NASH-related cirrhosis.

Systematic review: exercise-induced gastrointestinal syndrome - implications for health and intestinal disease

Abstract: SummaryBackground “Exercise-induced gastrointestinal syndrome” refers to disturbances of gastrointestinal integrity and function that are common features of strenuous exercise. Aim To systematically review the literature to establish the impact of acute exercise on markers of gastrointestinal integrity and function in healthy populations and those with chronic gastrointestinal conditions. Methods Search literature using five databases (PubMed, EBSCO, Web of Science, SPORTSdiscus, and Ovid Medline) to review publications that focused on the impact of acute exercise on markers of gastrointestinal injury, permeability, endotoxaemia, motility and malabsorption in healthy populations and populations with gastrointestinal diseases/disorders. Results As exercise intensity and duration increases, there is considerable evidence for increases in indices of intestinal injury, permeability and endotoxaemia, together with impairment of gastric emptying, slowing of small intestinal transit and malabsorption. The addition of heat stress and running mode appears to exacerbate these markers of gastrointestinal disturbance. Exercise stress of ≥2 hours at 60% VO2max appears to be the threshold whereby significant gastrointestinal perturbations manifest, irrespective of fitness status. Gastrointestinal symptoms, referable to upper- and lower-gastrointestinal tract, are common and a limiting factor in prolonged strenuous exercise. While there is evidence for health benefits of moderate exercise in patients with inflammatory bowel disease or functional gastrointestinal disorders, the safety of more strenuous exercise has not been established. Conclusions Strenuous exercise has a major reversible impact on gastrointestinal integrity and function of healthy populations. The safety and health implications of prolonged strenuous exercise in patients with chronic gastrointestinal diseases/disorders, while hypothetically worrying, has not been elucidated and requires further investigation.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

Abstract: SummaryBackground Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. Aim To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. Methods We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. Results A total of 12 RCTs were included in the meta-analysis (CD – 2 induction, 4 maintenance; UC – 8 induction, 5 maintenance). Duration of follow-up was 6–12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51–110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25–0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12–0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Conclusions Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease

Abstract: SummaryBackground Infliximab has been found to be efficacious in the treatment of fistulas in the setting of Crohn's disease, even though some patients do not benefit from therapy. Aim To assess the correlation between perianal fistula healing and trough levels of infliximab. Methods In this cross-sectional study, we identified patients with Crohn's disease who had perianal fistulas and were treated with infliximab for at least 24 weeks. We excluded patients who underwent a faecal diversion procedure or proctectomy. Predictive variables included demographics, disease phenotype, disease activity, infliximab levels, anti-infliximab antibodies. The primary outcome was fistula healing defined as the absence of drainage. The secondary outcome was complete fistula closure and mucosal healing. Results 117 patients were included. Patients with fistula healing had significantly higher median serum infliximab levels when compared to those with active fistulas [15.8 vs. 4.4 μg/mL, respectively (P < 0.0001)]. There was an incremental gain in fistula healing with higher infliximab levels. The AUC for the association between fistula healing and infliximab levels was 0.82 (P < 0.0001), while the AUC for the association of infliximab levels and fistula closure was 0.69 (P = 0.014). Patients with anti-infliximab antibodies had a lower chance of achieving fistula healing (OR: 0.04 [95%CI: 0.005–0.3], P < 0.001). Conclusions There is a significant association between serum infliximab levels and rates of fistula healing. Achieving infliximab levels ≥10.1 mcg/mL in patients with Crohn's disease and perianal fistulas may improve outcomes as part of a treat-to-target strategy.

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

Abstract: SummaryBackground Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

Abstract: SummaryBackground Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. Aim To determine whether FMT is effective and safe for the induction of remission in active UC. Methods Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). Results There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. Conclusions Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.

Review article: the human intestinal virome in health and disease

Abstract: SummaryBackground The human virome consists of animal-cell viruses causing transient infections, bacteriophage (phage) predators of bacteria and archaea, endogenous retroviruses and viruses causing persistent and latent infections. High-throughput, inexpensive, sensitive sequencing methods and metagenomics now make it possible to study the contribution dsDNA, ssDNA and RNA virus-like particles make to the human virome, and in particular the intestinal virome. Aim To review and evaluate the pioneering studies that have attempted to characterise the human virome and generated an increased interest in understanding how the intestinal virome might contribute to maintaining health, and the pathogenesis of chronic diseases. Methods Relevant virome-related articles were selected for review following extensive language- and date-unrestricted, electronic searches of the literature. Results The human intestinal virome is personalised and stable, and dominated by phages. It develops soon after birth in parallel with prokaryotic communities of the microbiota, becoming established during the first few years of life. By infecting specific populations of bacteria, phages can alter microbiota structure by killing host cells or altering their phenotype, enabling phages to contribute to maintaining intestinal homeostasis or microbial imbalance (dysbiosis), and the development of chronic infectious and autoimmune diseases including HIV infection and Crohn's disease, respectively. Conclusions Our understanding of the intestinal virome is fragmented and requires standardised methods for virus isolation and sequencing to provide a more complete picture of the virome, which is key to explaining the basis of virome-disease associations, and how enteric viruses can contribute to disease aetiologies and be rationalised as targets for interventions.

Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis

Abstract: SummaryIntroduction Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease course is not clearly defined. Aim To investigate the comparative efficacy of currently available inflammatory bowel disease (IBD) therapies to reduce hospitalisation and surgery. Methods We conducted a systematic review in MEDLINE/PubMed for randomised controlled trials (RCT) published between January 1980 and May 2016 examining efficacy of biological or immunomodulator therapy in IBD. We performed direct comparisons of pooled proportions of hospitalisation and surgery. Pair-wise comparisons using a random-effects Bayesian network meta-analysis were performed to assess comparative efficacy of different treatments. Results We identified seven randomised controlled trials (5 CD; 2 UC) comparing three biologics and one immunomodulator with placebo. In CD, anti-TNF biologics significantly reduced hospitalisation [Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.36–0.60] and surgery (OR 0.23, 95% CI 0.13–0.42) compared to placebo. No statistically significant reduction was noted with azathioprine or vedolizumab. Azathioprine was inferior to both infliximab and adalimumab in preventing CD-related hospitalisation (>97.5% probability). Anti-TNF biologics significantly reduced hospitalisation (OR 0.48, 95% CI 0.29–0.80) and surgery (OR 0.67, 95% CI 0.46–0.97) in UC. There were no statistically significant differences in the pair-wise comparisons between active treatments. Conclusions In CD and UC, anti-TNF biologics are efficacious in reducing the odds of hospitalisation by half and surgery by 33–77%. Azathioprine and vedolizumab were not associated with a similar improvement, but robust conclusions may be limited due to paucity of RCTs.

Sarcopenia is associated with severe liver fibrosis in patients with non‐alcoholic fatty liver disease

Abstract: SummaryBackground Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Aim To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. Methods We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females. Results The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3–F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P 50 (OR 6.53, CI 2.95–14.4, P < 0.001), IFG/Diabetes (OR 2.14, CI 1.05–4.35, P = 0.03) and NASH (OR 13.3, CI 1.64–108.1, P = 0.01). Similarly, a significant association was found between sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06–3.83, P = 0.03) after adjusting for confounders. Conclusions In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression.

Systematic review with meta‐analysis: risk factors for non‐alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients

Abstract: SummaryBackground The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. Methods We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. Results Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10−6) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10−10) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA-IR (0.52±0.094-unit increment), blood lipids (triglycerides: 48.37±3.6, P=10−10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10−7), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10−10, and waist circumference (5.88±0.4 cm, P=10−10); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids. Conclusion Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features.

Randomised clinical trial: faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy.

Abstract: ummary Background Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics. Aim To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product. Methods Seventy-two subjects with ≥3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling. Results Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days. Conclusions Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation.

Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth.

Abstract: SummaryBackground Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. Aim To perform a systematic review and meta-analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients. Methods MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined. Results Thirty-two studies involving 1331 patients were included. The overall eradication rate according to intention-to-treat analysis was 70.8% (95% CI: 61.4–78.2; I2 = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5–79.8; I2 = 87.5%). Meta-regression identified three covariates (drug dose, study design and co-therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3–7.5; I2 = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7–86.9; I2 = 91.3%). Conclusions Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.

Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn's disease: real world experience from a multicentre cohort

Abstract: SummaryBackground Ustekinumab is a monoclonal antibody targeting interleukins-12 and -23, with efficacy in Crohn's disease (CD) demonstrated in clinical trials. Aim To assess the real-world clinical, endoscopic and radiographic response and remission outcomes achieved with ustekinumab in medically-refractory CD. Methods A retrospective multicentre cohort study was performed on CD patients receiving ustekinumab between 2011 and 2016. The primary outcome was achievement of clinical and objective steroid-free response and remission at 3, 6 and 12 months. Clinical response and remission were defined by reduction in Harvey Bradshaw Index (HBI) of ≥3 points and an HBI ≤4 points respectively. Objective response was defined by improvement in endoscopic or radiographic CD, as assessed by ileocolonoscopy, contrast-enhanced ultrasound or CT/MR enterography. Objective remission was defined by endoscopic mucosal healing or complete resolution of inflammatory parameters on radiographic assessment. Results A total of 167 CD patients were treated with ustekinumab. 95.2% (159/167) previously failed anti-TNF therapy. Median follow-up was 45.6 weeks (IQR: 24.4–88.9). At 3 months, clinical response was achieved in 38.9% (65/167) and remission in 15.0% (25/167) of patients. At 6 months, clinical response was achieved in 60.3% (91/151) and remission in 25.2% (38/151) of patients. At 12 months, clinical response was achieved in 59.5% (66/111) and remission in 27.9% (31/111) of patients. Endoscopic or radiographic response was demonstrated in 54.5% (67/123) at 6 months and 55.8% (48/86) of patients at 12 months. Conclusions Ustekinumab is an effective therapeutic option for inducing and maintaining clinical, endoscopic and radiographic response in patients with Crohn's disease failing anti-TNF therapy.

Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis

Abstract: SummaryBackground Breastfeeding is a modifiable factor that may influence development of inflammatory bowel diseases. However, literature on this has been inconsistent and not accounted for heterogeneity in populations and exposure. Aim To conduct a meta-analysis to examine the association between breastfeeding in infancy and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods A systematic search of Medline/PubMed and Embase was performed for full text, English-language literature through November 2016. Studies were included if they described breastfeeding in infancy in patients with CD or UC, and healthy controls. Data were pooled using a random effects model for analysis. Results A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months. Conclusion Breastfeeding in infancy protects against the development of CD and ulcerative colitis.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

Abstract: SummaryBackground We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. Aims To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. Methods Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. Results At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. Conclusion Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.

Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD.

Abstract: SummaryBackground The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. Aim To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. Methods We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. Results LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<−1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. Conclusion The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD.

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study

Abstract: SummaryBackground Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. Aim To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. Methods We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. Results Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. Conclusions Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis: mid-term follow-up and factors predicting outcome.

Abstract: SummaryBackground Gastric peroral endoscopic pyloromyotomy (G-POEM) was introduced for treating refractory gastroparesis. Aim The presented series focused on clinical mid-term efficacy and predictive outcomes factors. Methods This was a single centre study of 29 patients operated on between January 2014 and April 2016, with disturbed gastric emptying scintigraphy (GES) and/or elevated Gastroparesis Cardinal Symptoms Index (GCSI). The procedures were performed as previously described. The primary endpoint was the efficacy at 3 and 6 months, based on GCSI and symptoms. The secondary endpoints were GES evolution, procedure reproducibility and safety, and identification of predictive factors for success. Results There were 10 men, 19 women (mean age 52.8±18). The technical success rate was 100% (average 47 minutes). There were two complications managed conservatively: one bleeding and one abscess. The median follow-up was 10±6.4 months. The clinical success rate was 79% at 3 months, 69% at 6 months, with a significant decrease in the mean GCSI compared to pre-operatively (3.3±0.9 vs 1±1.2 and 1.1±0.9 respectively). The GES (n=23) normalised in 70% of cases, with a significant improvement of the mean half emptying time and retention at 2 hours, and a discordance in 21% of the cases. In univariate analysis, diabetes and female gender were significantly associated with risk of failure, but not confirmed in multivariate analysis. Conclusions The mid-term efficacy of G-POEM reaches 70% at 6 months. The procedure remains reproducible and safe. Diabetes and female gender were predictive of failure.

Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis.

Abstract: Background The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test is still uncertain. Aim To assess the diagnostic performance of the serum panel test for the diagnosis of atrophic gastritis. Methods Medline via PubMed, Embase, Scopus, Cochrane Library databases and abstracts of international conferences proceedings were searched from January 1995 to December 2016 using the primary keywords “pepsinogens,” “gastrin,” “atrophic gastritis,” “gastric precancerous lesions.” Studies were included if they assessed the accuracy of the serum panel test for the diagnosis of atrophic gastritis using histology according to the updated Sydney System as reference standard. Results Twenty studies with a total of 4241 subjects assessed the performance of serum panel test for the diagnosis of atrophic gastritis regardless of the site in the stomach. The summary sensitivity was 74.7% (95% confidence interval (CI), 62.0-84.3) and the specificity was 95.6% (95%CI, 92.6-97.4). With a prevalence of atrophic gastritis of 27% (median prevalence across the studies), the negative predictive value was 91%. Few studies with small sample size assessed the performance of the test in detecting the site of atrophic gastritis. Conclusions The combination of pepsinogen, gastrin-17 and anti-H. pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis. This test may be used for screening subjects or populations at high risk of gastric cancer for atrophic gastritis; however, a cost-effectiveness analysis is needed.

Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease

Abstract: SummaryBackground Vedolizumab is a gut-selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. Aim To assess pregnancy outcomes in females and partners of males who received vedolizumab. Methods All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post-marketing setting (to 19 November 2015) were analysed. Results Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab-treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single-dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post-marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on-going or reported undocumented outcomes. Conclusions Initial analysis, limited by sample size and follow-up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.

Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population.

Abstract: SummaryBackground Non-alcoholic fatty liver disease (NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Aim To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. Methods We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve (AUROC) of models in validation group were compared. Results Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. Conclusions NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.

Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication

Abstract: Background In order to increase eradication rates, vonoprazan, a novel potassium-competitive acid blocker, has been used in Helicobacter pylori eradication therapy. Aim To summarise the results of the efficacy of vonoprazan-based triple therapy, helping clinicians to better understand the benefit of vonoprazan in the treatment of H. pylori infection. Methods We conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords “vonoprazan,” “takecab”, “TAK-438,” “potassium,” “competitive,” “potassium-competitive,” “Helicobacter,” and “pylori.” Studies were included if they evaluated the eradication rate between the vonoprazan-based and proton pump inhibitor (PPI)-based triple therapies. Results Ten studies and 10 644 patients were evaluated. The crude H. pylori eradication rate determined by intention-to-treat analysis was 87.9% and 72.8% in the vonoprazan-based triple therapy and PPI-based triple therapy respectively. The eradication rate of the vonoprazan-based triple therapy was superior to that of the PPI-based triple therapy (pooled risk ratio [RR] [95% confidence interval (CI)]=1.19 [1.15-1.24]) In addition, there was no significant difference in dropout rate due to adverse event between the regimens (pooled RR of the vonoprazan-based triple therapy [95% CI]=0.69 [0.23-2.03]). The incidence of any adverse events also did not differ between the regimens (pooled RR [95% CI]=1.02 [0.78-1.34]). Conclusions The vonoprazan-based triple therapy showed superior efficacy in terms of H. pylori eradication as compared to the PPI-based triple therapy. In addition, the vonoprazan-based triple therapy showed comparable tolerability and incidence of adverse events.

Chronic opioid use is associated with altered gut microbiota and predicts readmissions in patients with cirrhosis.

Abstract: SummaryBackground Opioid use is epidemic in cirrhosis, which could precipitate hepatic encephalopathy (HE) potentially through gut dysbiosis and inflammation. Aim To define the effect of opioids on readmissions and on gut microbiota composition and functionality. Methods Cohort 1 had 200 cirrhotic in-patients (with/without opioid use) followed prospectively through the index hospitalisation and 6 months post discharge. Readmissions (HE-related/unrelated) were compared between patients discharged on opioids compared to the rest, including using a multi-variable analysis. Cohort 2 consisted of 72 cirrhotics on chronic opioids who were age/model for end-stage liver disease (MELD) and prior HE-balanced with 72 cirrhotics not on opioids. Stool microbiota composition (multi-tagged sequencing), predicted functionality (PiCRUST), endotoxemia and systemic inflammation (IL-6, IL-17) were compared. Results Cohort 1: Chronic opioid use was statistically similar between those admitted with/without HE, and was judged to be an HE precipitant in <5% of cases during the index hospitalisation. Of the 144 patients alive at 6 months, 82 were readmitted. The opioid users had a significantly higher all cause (69% vs. 48%, P = 0.008), but not HE-related readmissions (30% vs. 41%, P = 0.30). On regression, opioid therapy and female gender were predictive of readmission independent of MELD score and previous HE. Cohort 2: Significant dysbiosis was noted in the opioid cohort, especially in HE+opioid patients with lower autochthonous taxa and Bacteroidaceae relative abundance. PiCRUST showed highest aromatic amino acid and endotoxin production in opioid users. Opioid users also had higher endotoxemia and IL-6 but not IL-17. Conclusion Chronic opioid use in cirrhosis is associated with increased endotoxemia, dysbiosis and all-cause readmissions.

Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn's disease.

Abstract: Background Despite potential adverse-events in a paediatric population, corticosteroids are used to induce remission in paediatric Crohn's disease. Exclusive enteral nutrition also induces remission, but is infrequently used in the USA because corticosteroids are considered the superior therapy. New data have become available since the publication of the most recent meta-analysis in 2007. Aim To see if current literature supports the use of EEN versus CS in paediatric populations. Methods All studies with comparator arms of exclusive enteral nutrition and an exclusive corticosteroids, with remission clearly defined were identified by searching eight online databases. Results Of 2795 identified sources, nine studies met our inclusion criteria. Eight of these (n = 451), had data that could be abstracted into our meta-analysis. Exclusive enteral nutrition was as effective as corticosteroids in inducing remission (OR = 1.26 [95% CI 0.77, 2.05]) in paediatric Crohn's disease. There was no difference between Exclusive enteral nutrition and corticosteroids efficacy when comparing newly diagnosed Crohn's (OR = 1.61 [95% CI .87, 2.98]) or relapsed (OR = 0.76 [95% CI .29-1.98]). Intestinal healing was significantly more likely among patients receiving Exclusive enteral nutrition compared to corticosteroids (OR = 4.5 [95% CI 1.64, 12.32]). There was no difference in the frequency of biomarker normalisation including CRP (OR = 0.85 [95% CI .44, 1.67]) and faecal calprotectin (OR 2.79 [95% CI .79-10.90]). Conclusions There is no difference in efficacy between Exclusive enteral nutrition and corticosteroids in induction of remission in Crohn's disease in a paediatric population. Exploratory analyses suggest that a greater proportion of patients treated with exclusive enteral nutrition achieved mucosal healing.

Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open‐label, prospective and randomised clinical trial

Abstract: SummaryBackground Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). Aim To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. Methods Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. Results Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1 year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45 μg/mL, P=.9) and in group AZA down (3.95 vs 3.60 μg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15 μg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN <105 pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. Conclusions Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.

The incidence of inflammatory bowel disease in Denmark 1980–2013: a nationwide cohort study

Abstract: SummaryBackground Globally, the incidence rates of inflammatory bowel disease (IBD) are increasing; however, data from high-incidence areas are conflicting. Previous studies in Denmark have assessed incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) using short observation periods. Aim To investigate trends in IBD incidence in Denmark over a thirty-year period using nationwide data. Methods Patients diagnosed with CD or UC in Denmark between 1980 and 2013 were identified in the Danish National Patient Registry (NPR) and included in a nationwide cohort. Incidence rates estimated using different numbers of National Patient Registry records (≥1, 2, 3 or 4) required for case definition were compared. Results From 1980 to 2013 the incidence of CD increased from 5.2 (95% CI: 5.0–5.4) per 100 000 to 9.1 (95% CI: 8.7–9.5) per 100 000 and the incidence of UC increased from 10.7 (95% CI: 10.4–11.0) per 100 000 to 18.6 (95% CI: 18.0–19.2) per 100 000. The increased incidence in CD and UC was independent of gender. The annual increase in incidence rate was greatest in patients aged <15 years for CD and those older than 15 years for UC. For both CD and UC the incidence rates for females were significantly higher than for males. The number of registry records chosen to define IBD cases greatly influenced incidence estimates. Conclusions The incidence of IBD in Denmark continues to increase and is among the highest in the world. Using at ≥2 records of IBD diagnosis in the Danish National Patient Registry will result in more valid incidence estimates.

Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease.

Abstract: SummaryBackground Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. Aim To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients. Methods We retrospectively collected measurements of infliximab or adalimumab serum concentrations and anti-drug antibodies to identify anti-drug positive patients with loss response who were given an immunomodulator. Results Anti-drug antibodies against infliximab and adalimumab were detected in 98/376 (26%) and in 61/226 (27%) patients, respectively. Immunomodulators were given to 17/159 patients. Clinical response was recaptured in 6/10 patients receiving a thiopurine and in all (7/7) patients receiving methotrexate. In 7/8 patients on infliximab, serum concentrations increased (median 2.84 μg/mL; IQR: 1.19–4.98) and in 6/9 patients on adalimumab (median 3.10 μg/mL; IQR: 1.45–4.45). This was accompanied by a decrease in anti-drug antibodies to undetectable levels (median 11 months for both anti-TNF agents). In 23 patients, no immunomodulator was added but anti-TNF interval was shortened (17/23) or dosage was increased (6/23), which resulted in a clinical response in 10/17 and 2/6 patients, respectively. Conclusion In 77% of IBD patients with loss of response due to immunogenicity, addition of immunomodulator resulted in undetectable anti-drug antibody levels, increased serum drug concentrations and regained clinical response. This strategy should be considered in this patient population before switching to other agents.

Predictors of response to a low‐FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance

Abstract: SummaryBackground Diets low in fermentable sugars (low-FODMAP diets) are increasingly adopted by patients with functional gastrointestinal disorders (FGID), but outcome predictors are unclear. Aim To identify factors predictive of an efficacious response to a low-FODMAP diet in FGID patients with fructose or lactose intolerance thereby gaining insights into underlying mechanisms. Methods Fructose and lactose breath tests were performed in FGID patients to determine intolerance (positive symptom score) and malabsorption (increased hydrogen or methane concentrations). Patients with fructose or lactose intolerance consumed a low-FODMAP diet and global adequate symptom relief was assessed after 6–8 weeks and correlated with pre-diet clinical symptoms and breath test results. Results A total of 81% of 584 patients completing the low-FODMAP diet achieved adequate relief, without significant differences between FGID subgroups or types of intolerance. Univariate analysis yielded predictive factors in fructose intolerance (chronic diarrhoea and pruritus, peak methane concentrations and fullness during breath tests) and lactose intolerance (peak hydrogen and methane concentrations and flatulence during breath tests). Using multivariate analysis, symptom relief was independently and positively predicted in fructose intolerance by chronic diarrhoea [odds ratio (95% confidence intervals): 2.62 (1.31–5.27), P = 0.007] and peak breath methane concentrations [1.53 (1.02–2.29), P = 0.042], and negatively predicted by chronic nausea [0.33 (0.16–0.67), P = 0.002]. No independent predictive factors emerged for lactose intolerance. Conclusions Adequate global symptom relief was achieved with a low-FODMAP diet in a large majority of functional gastrointestinal disorders patients with fructose or lactose intolerance. Independent predictors of a satisfactory dietary outcome were only seen in fructose intolerant patients, and were indicative of changes in intestinal host or microbiome metabolism.