Showing papers in "BMJ Open Gastroenterology in 2017"

Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention

Abstract: Objective The colonic microbiota is altered in patients with colorectal cancer (CRC). We investigated the microbiota composition of patients with colon cancer compared with controls devoid of neoplastic or inflammatory disease and the potential to modify the colonic microbiota with probiotics. Design Biopsy samples were obtained from the normal mucosa and tumour during colonoscopy from 15 patients with colon cancer. Subsequent patient-matched samples were taken at surgery from the tumour and nearby mucosa from the patients with cancer, eight of whom had received two daily tablets totalling 1.4×1010 CFUs Bifidobacterium lactis Bl-04 and 7×109 CFUs Lactobacillus acidophilus NCFM. Faecal samples were obtained after colonoscopy prior to starting the intervention and at surgery. In addition, 21 mucosal biopsies from non-cancer controls were obtained during colonoscopy followed by later faecal samples. The colonic and faecal microbiota was assessed by 16S rRNA gene amplicon sequencing. Results The tumour microbiota was characterised by increased microbial diversity and enrichment of several taxa including Fusobacterium, Selenomonas and Peptostreptococcus compared with the control microbiota. Patients with colon cancer that received probiotics had an increased abundance of butyrate-producing bacteria, especially Faecalibacterium and Clostridiales spp in the tumour, non-tumour mucosa and faecal microbiota. CRC-associated genera such as Fusobacterium and Peptostreptococcus tended to be reduced in the faecal microbiota of patients that received probiotics. Conclusions Patients with colon cancer harbour a distinct microbiota signature in the tumour tissue and nearby mucosa, which was altered with probiotic intervention. Our results show promise for potential therapeutic benefits in CRC by manipulation of the microbiota. Trial registration number NCT03072641; Results.

Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia.

Abstract: Objective The objective of this study was to comparatively analyse the gastric fluid (GF) microbiota between patients with functional dyspepsia (FD) and healthy controls (HC), and to assess the effect of probiotics on the microbiota. Design Twenty-four Japanese patients with FD who met the Rome III definition and 21 age-matched and gender-matched HC volunteers were enrolled. The patients with FD had been treated with LG21, a probiotic strain. The GF was sampled after an overnight fast using a nasogastric tube. The bile acids concentration was determined by ELISA. The V3-V4 region of 16S rRNA gene was amplified using bacterial DNA from the GF, and then about 30 000 high-quality amplicons per sample were grouped into operational taxonomic units for analyses. Results The ratio of GF samples in which the bile acids were detectable was significantly greater in the FD than in the HC groups. In the bacterial composition analysis at the phylum level, the GF microbiota had a Bacteroidetes > Proteobacteria abundance and an absence of Acidobacteria in the FD group, in contrast, the GF microbiota had a Bacteroidetes Proteobacteria abundance and the presence of Acidobacteria in the HC group. Probiotic therapy in patients with FD shifted the composition of the GF microbiota to that observed in the HC volunteers. Conclusions Alteration in the GF microbiota was found in patients with FD compared with HC volunteers. Reflux of the small intestinal contents, including bile acid and intestinal bacteria, to the stomach was suggested to induce a bacterial composition change and be involved in the pathophysiology underlying FD. Probiotics appear effective in the treatment of FD through the normalisation of gastric microbiota. Trial registration number UMINCTR 000022026; Results.

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review

Abstract: Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with prevalence above 30% in many adult populations. Strongly associated with obesity, weight loss through diet and physical activity is the mainstay of its management. Weight loss can be difficult to achieve and maintain however, and uncertainty exists as to which lifestyle changes are most effective. Objective The aim of this work was to systematically evaluate randomised controlled trials assessing diet, exercise or combination interventions aimed at reducing steatosis or markers of NAFLD activity. Design Medline, Scopus and Cochrane databases were searched from 1 January 1980 through to 31 July 2016, for intervention trials assessing the effects of diet, weight loss, exercise or any combination thereof, on NAFLD disease markers in human adults. Risk of publication bias and study quality was assessed using the American Dietetic Association Quality Criteria Checklist. Results From a total of...

Mechanisms of liver disease in patients infected with HIV

Abstract: Objective To describe the various mechanisms of liver disease in patients with HIV infection, and to link these mechanisms to disease states which may utilise them. Background Non-AIDS causes of morbidity and mortality are becoming increasingly common in patients chronically infected with HIV. In particular, liver-related diseases have risen to become one of the leading causes of non-AIDS-related death. A thorough understanding of the mechanisms driving the development of liver disease in these patients is essential when evaluating and caring for these patients. Methods The literature regarding mechanisms of liver disease by which different disease entities may cause hepatic injury and fibrosis was reviewed and synthesised. Results A number of discrete mechanisms of injury were identified, to include: oxidative stress, mitochondrial injury, lipotoxicity, immune-mediated injury, cytotoxicity, toxic metabolite accumulation, gut microbial translocation, systemic inflammation, senescence and nodular regenerative hyperplasia. Disease states may use any number of these mechanisms to exert their effect on the liver. Conclusions The mechanisms by which liver injury may occur in patients with HIV infection are numerous. Most disease states use multiple mechanisms to cause hepatic injury and fibrosis.

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

Abstract: Objective To compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms. Design Adult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire. Results The UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5–16.4) and 7.0 (1.0–19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts. Conclusions The present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state.

Changes in the gut microbiota composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy.

Abstract: Objective To investigate the influence of antimicrobials on both the gut microbiota structure and the plasma ghrelin level using Helicobacter pylori-infected patients who underwent eradication therapy. Design Twenty H. pylori-infected patients (mean age 68.3 years old) who underwent eradication therapy participated in the study. For the therapy, patients had 1 week of triple therapy consisting of amoxicillin, clarithromycin and proton-pump inhibitors. Stool and blood samples were obtained before (S1), immediately after (S2) and/or 3 months after (S3) the therapies. The concentrations of ghrelin and leptin in the blood were assayed using an ELISA. The V3-V4 region of the 16S rRNA gene was amplified using bacterial DNA from the stool, and about 50 000 high-quality amplicons per sample were grouped into operational taxonomic units for bacteriological analyses. Results The Bacteroidetes:Firmicutes (B:F) ratio was significantly greater at S3 than S1 (P Conclusions Changes in the gut microbiota, such as the B:F ratio after treatment with antimicrobials, might cause a change in the plasma ghrelin level, as the direct and earliest target of antimicrobials would be the microbiota rather than the hormone-secreting system.

How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes.

Abstract: Objectives Bile acid diarrhoea (BAD) is an underdiagnosed condition producing diarrhoea, urgency and fear of faecal incontinence. How patients experience these symptoms has not previously been studied. Bile Acid Malabsorption (BAM) Support UK was established in 2015 as a national charity with objectives including to provide details regarding how BAD affects patients, to improve earlier recognition and clinical management. Design, setting and main outcome A questionnaire was collected anonymously by BAM Support UK and the Bile Salt Malabsorption Facebook group over 4 weeks at the end of 2015. It comprised 56 questions and aimed to inform patients and clinicians about how BAD affects the respondents. Results The first 100 responses were analysed. 91% of the respondents reported a diagnosis of BAD. 58% of total respondents diagnosed following a Selenium-homocholic acid taurine scan, 69% were diagnosed by a gastroenterologist, with type 2 and 3 BAD comprising 38% and 37%, respectively, of total respondents. Symptoms had been experienced for more than 5 years before diagnosis in 44% of respondents. Following treatment, usually with bile acid sequestrants, 60% of participants reported improvement of diarrhoea and most reported their mental health has been positively impacted. Just over half of the cohort felt as though their symptoms had been dismissed during clinical consultations and 28% felt their GPs were unaware of BAD. Conclusions BAD requires more recognition by clinicians to address the current delays in diagnosis. Treatment improves physical and mental symptoms in the majority of participants.

Combination therapy with vedolizumab and etanercept in a patient with pouchitis and spondylarthritis

Abstract: Inflammatory bowel disease is frequently associated with spondylarthritis (SpA). It has been discussed that α4/β7 expressing lymphocytes are involved in the aetiology of SpA. We report a case of a successful combination therapy of vedolizumab (VDZ) and etanercept (ETA) in a patient with ulcerative colitis with pouchitis and SpA. In our case VDZ was effective for pouchitis and ineffective for SpA. The combination with ETA might be a useful treatment strategy to control both diseases and first indications suggest that it is safe. α4/β7 Expressing lymphocytes are most likely not associated in the aetiology of SpA.

Weight regain after Roux-en-Y gastric bypass has a large negative impact on the Bariatric Quality of Life Index.

Abstract: Background Despite initial successful weight loss, some patients may experience weight regain following Roux-en-Y gastric bypass (RYGB). Objective To assess the impact of weight regain on bariatric patients’ quality of life (QoL). Methods This was a prospective cross-sectional study. Fifty-six consecutive RYGB patients were recruited and divided into weight-regain and weight-stable cohorts. QoL was assessed using the Bariatric Quality of Life (BQL) questionnaire. The BQL Index scores of the weight-regain and weight-stable groups were compared using Student’s t-test. Additionally, the BQL Index score of the weight-regain group was compared with that of historical prebariatric patients. Predictors of BQL were assessed using univariate and multivariate linear regression analyses. Results Of 56 RYGB patients, 41 (73%) had weight regain. On average, patients had body mass index (BMI) of 37 ±7.5 kg/m2 and gained 34 ±26% of maximal weight initially lost. Weight-regain patients had lower BQL Index scores than weight-stable patients (44.8±6 vs 53±7, p Conclusion Weight regain had a negative impact on bariatric patients’ QoL. Patients who regained at least 15% of maximal weight lost appeared to have as low QoL as those who had not undergone bariatric surgery despite a lower BMI.

Utility of the wireless motility capsule and lactulose breath testing in the evaluation of patients with Parkinson's disease who present with functional gastrointestinal symptoms.

Abstract: Background The aetiology and origin of gastrointestinal symptoms in Parkinson's disease (PD) remains poorly understood. Gastroparesis, small bowel transit delay and bacterial overgrowth may, individually or collectively, play a role. Aims In patients with PD and functional gastrointestinal symptoms, we aimed to determine the utility of the wireless motility capsule and lactulose breath tests in further defining their symptoms' aetiology. Methods In this retrospective cohort study, consecutive patients with PD and functional gastrointestinal symptoms underwent clinical assessment, as well as wireless motility capsule and lactulose breath testing using standard protocols. Results We studied 65 patients with PD and various gastrointestinal symptoms. 35% exhibited gastroparesis by the wireless motility capsule study, 20% small bowel transit delay, while 8% had combined transit abnormalities, suggestive of overlapping gastric and small bowel dysmotility. Small bowel bacterial overgrowth was seen in 34% of case...

Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance?

Abstract: Background The British Society of Gastroenterology guidelines recommend taking at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy if coeliac disease (CD) is suspected and it has been shown to increase the diagnostic yield of CD We assessed the compliance to these guidelines within our institution We then applied measures to improve our compliance rate and assessed the resulting impact on our diagnostic rate of CD Methods We performed a retrospective audit of electronic records for all patients, with no prior diagnosis of CD, who underwent UGI endoscopy with duodenal biopsies between August 2014 and May 2015 We implemented measures to raise awareness among endoscopy users at our institution and carried out a reaudit between February and May 2016 Results 924 patients were found to be eligible in the first part of the study and 278 in the second part The proportion of patients who had ≥4 biopsy specimens submitted increased from 219% to 608% (p Conclusions Our study suggests that taking

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial.

Abstract: Background Patients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in patients with IBS guided by a leucocyte activation test. Methods This is a parallel-group, double-blind, randomised controlled trial of 58 adults with IBS seen at an academic health centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte activation test; individual foods were reported to produce positive or negative results. Participants were randomised to a 4-week diet with either individualised guidance to eliminate foods with positive assay results and allow foods with negative assay results (intervention), or with individualised guidance, matched in rigour and complexity, to eliminate foods with negative assay results and allow foods with positive assay results (comparison). The primary outcome was between-group differences in the IBS Global Improvement Scale (GIS). Secondary outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An aptamer-based proteomic analysis was conducted in strong responders. Results The intervention group had significantly greater increases in mean GIS score after 4 weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had significantly greater reductions in mean SSS score at 4 weeks (–61.78 vs comparison; 95% CI –4.43 to –119.14; p=0.04) and 8 weeks (–66.42 vs comparison; 95% CI –5.75 to –127.09; p=0.03). There were no significant differences between intervention and comparison groups in mean AR or QOL scores. A reduction in neutrophil elastase concentration was associated with reduced symptoms. Conclusions Elimination diets guided by leucocyte activation tests reduced symptoms. These findings could lead to insights into the pathophysiology of IBS. Trial registration number NCT02186743.

Diagnostic accuracy of high-resolution MRI as a method to predict potentially safe endoscopic and surgical planes in patients with early rectal cancer.

Abstract: Introduction Early rectal cancer (ERC) assessment should include prediction of the potential excision plane to safely remove lesions with clear deep margins and feasibility of organ preservation. Method MRI accuracy for differentiating ≤T1sm2 (partially preserved submucosa) or ≤T2 (partially preserved muscularis) versus >T2 tumours was compared with the gold standard of pT stage T1sm1/2 versus ≤pT2 versus >pT2. N stage was also compared. The MRI protocol employed a standard surface phased array coil with a high resolution (0.6×0.6×3 mm resolution). The staging data were analysed from a prospectively recorded database of all ERC (≤mrT3b) treated by primary surgery. Results Of 65 0.7 suggesting good agreement. 44 out of 65 patients underwent radical surgery and 22 out of 44 were ≤mrT2. MRI accuracy to predict lymph node status was 84% (95% CI 70% to 92%), PPV 71% and NPV 90%. Among the 21 out of 65 (32%) patients undergoing local excision or TEM, 20 out of 21 were staged as MR≤T2 and confirmed as such by pathology. On follow-up, none had relapse. If the decision had been made to offer local excision on MRI TN staging rather than clinical assessment, a significant increase in organ preservation surgery from 32% to 60% would have been observed (difference 23%, 95% CI 9% to 35%). Conclusions MRI is a useful tool for multidisciplinary teams (MDTs) wishing to optimise treatment options for ERC; these study findings will be validated in a prospective multicentre trial.

Prevalence and screening for anaemia in mild to moderate Crohn's disease and ulcerative colitis in the United States, 2010-2014

Abstract: Background and aims Anaemia affects up to 74% patients with Crohn9s disease (CD) and ulcerative colitis (UC) and is correlated with decreased quality of life. The European Crohn9s and Colitis Organisation (ECCO) recommends at least annual screening for iron-deficiency anaemia. We aimed to determine the prevalence of anaemia, frequency of anaemia screening and factors associated with anaemia in a retrospective study of mild to moderate inflammatory bowel disease (IBD) in the USA. Methods Adults with at least two outpatient encounters for IBD between 2010 through 2014 who contributed laboratory information were identified from MarketScan, a US commercial claims database. Hospitalised patients were considered severe and excluded from the study. WHO criteria defined anaemia. Iron-deficiency anaemia was evaluated using ferritin and C reactive protein. Results The eligible population included 17 059 adults, 43.9% with CD. During the 2-year median follow-up period, 68.1% of patients with CD and 65.3% of patients with UC were screened for anaemia. The prevalence of anaemia among those screened was 32.4% in CD and 27.6% in UC. Among 669 persons with sufficient information, 79.2% of those with CD and 85.1% of those with UC had iron-deficiency anaemia. Factors associated with anaemia were similar for those with CD and UC and included ≥6 IBD-related outpatient visits, female sex, age and smoking. Conclusions More than 30% of patients with IBD in the USA were not screened for anaemia during a 2-year period. Approximately 82% of anaemic patients were iron deficient, although the absence of ferritin results limited the findings. Incorporation of screening for anaemia and, in particular, iron deficiency, should be a component of international treatment guidelines.

Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958–2014

Abstract: Objective To determine trends in diagnosis of coeliac disease (CD) in patients attending a single centre 1958–2014 and provide figures for prevalence and incidence in those born in Derby city over 4 decades. To explore a link between deprivation and prevalence and characteristics of CD in Asians. Design An unselected, consecutive series of 2410 adult patients with CD diagnosed in the catchment area of the Derby hospitals was identified. 1077 born within Derby city identified by postcodes was used to determine changes in prevalence and incidence over 4 decades. 191 patients were Asian. Population numbers were obtained from National Census information. Results In the quinquennium 2010–2014, 20 times more patients were diagnosed than during 1975–1979. 27% were diagnosed at ≥60 years. A paucity of diagnoses in young men was observed. Women were diagnosed most often in age band ≥35 Conclusions The dramatic increase in number of patients with CD presents challenges for follow-up and new models of care need to be explored. Healthcare workers should be alert to the diagnosis in young men and elderly Asians. A dedicated coeliac clinic is an excellent facility to increase diagnosis rates.

Impact of feedback and monitoring on colonoscopy withdrawal times and polyp detection rates.

Abstract: Background Previous studies have shown colonoscopy withdrawal time (WT) to be a reliable surrogate indicator for polyp detection rate (PDR) and adenoma detection rate (ADR) in colonoscopy. Our aim was to assess the impact of feedback and monitoring of WT on PDR in routine colonoscopies with long-term follow-up. Materials and methods A total of 307 colonoscopies were performed in three separate clinical scenarios. First, PDR and WT were recorded without the staff being aware of the specific objective of the study. Before the second scenario, the staff was given interventional information and feedback on WTs and PDRs from the first scenario and was encouraged to aim for a minimum WT of 8 min. Retention of knowledge gained was reassessed in the third scenario 1 year later. Results The PDR in the first two scenarios differed significantly (p 0.05). The increase in PDR between the first and second scenarios was retained in the third follow-up scenario 1 year later where the WT of both polyp-positive and polyp-negative colonoscopies was found to be longer. Conclusions PDR almost doubled from the first to the second scenario of a real-life colonoscopy setting, indicating that awareness of WT is crucial. The knowledge gained from this intervention in routine practice was even retained after a year.

Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines.

Abstract: Background and aims Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. Methods We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. Results All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCC Conclusions Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed.

Non-acid gastro-oesophageal reflux is associated with squamous cell carcinoma of the oesophagus.

Abstract: Introduction Squamous cell carcinoma of the oesophagus is a common cancer among South Africans. Due to the absence of effective screening and surveillance programme for early detection and late presentation, squamous cell carcinoma of the oesophagus is usually diagnosed at an advanced stage or when metastasis has already occurred. The 5-year survival is often quoted at 5%–10%, which is poor. Objectives To determine the association between oesophageal squamous cell carcinoma (OSCC) and non-acid gastro-oesophageal reflux disease. Methods Study design A cross-sectional case–control analytical study of patients referred to the Gastroenterology Division of Steve Biko Academic Hospital in Pretoria, South Africa. All patients had combined multichannel impedance and pH studies done and interpreted after upper gastroscopy using the American College of Gastroenterology guidelines by two clinicians. Results Thirty-two patients with OSCC were recruited: non-acid reflux was found in 23 patients (73%), acid reflux in 2 patients (6%) and 7 patients (22%) had normal multichannel impedance and pH studies. Forty-nine patients matched by age, gender and race were recruited as a control group. Non-acid reflux was found in 11 patients (22%), acid reflux in 31 patients (63%) and 7 patients (14%) had normal multichannel impedance and pH monitoring study. Conclusion The significance of the association between non-acid reflux and OSCC was tested using χ 2 , and simple logistic regression was used to adjust for the effects of potential confounders. The OR of developing OSCC in patients with non-acid gastro-oesophageal reflux was 8.8 (95% CI 3.2 to 24.5, P Alcohol and smoking had no effect on these results.

Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: a systematic review

Abstract: Aim The aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin. Methods We searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy. Results Of the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis. Conclusions Moderate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.

An educational tool for the prophylaxis of hepatic encephalopathy

Abstract: Background Providing structured information for the understanding of hepatic encephalopathy (HE) might be relevant to the prevention and management of the syndrome. The aim of our study was to design a brief, structured educational intervention and evaluate its usefulness in preventing HE-related hospitalisation over time. Methods Thirty-nine cirrhotic outpatients with a history of HE were enrolled and randomly assigned to an intervention (group A; n=20) or control group (group B; n=19). All of them underwent evaluation of HE (clinical and quantitative neuropsychiatric assessment) and completed the Questionnaire on the Awareness of Encephalopathy. A 15 min educational session was then provided to patients in group A, including basic information on the pathophysiology, hygienic and medical management of HE. Results No demographic/clinical differences were observed at baseline between the two groups. Similarly, there were no significant differences in HE-related information available at baseline between the two groups; knowledge of HE was limited in both. The intervention was highly effective in increasing patients’ understanding of treatment of the condition (from 5% to 80%). The educational intervention also reduced the risk of developing an episode of HE over a period of 12 months. Conclusion The educational intervention confirmed the poor knowledge of patients with previous HE about their condition, served as a tool to increase patients’ awareness, and minimised HE-related readmission rates over a period of 1 year.

Corticosteroid use and mortality risk in patients with perforated colonic diverticular disease: a population-based cohort study

Abstract: Background Corticosteroids are a potential risk factor for mortality in patients with perforated diverticular disease, due to blinding of disease severity, hampered wound healing or adrenal insufficiency. We examined mortality in corticosteroid users and non-users among patients with perforated diverticular disease. Methods A cohort study based on medical databases including all patients ≥18 years in Denmark (source population 5 289 261 inhabitants) admitted to a hospital with incident perforated diverticular disease between 2005 and 2013. 7-day, 1-month, 3-month and 1-year mortality risks in corticosteroid users and non-users were calculated using the Kaplan–Meier method, and compared with Cox proportional hazard regression adjusted for age, sex and comorbidities. Results The study included 4640 patients with perforated diverticular disease. Of these, 3743 (80.7%) had not used corticosteroids in the year before admission and 725 (15.6%) had been exposed to systemic corticosteroid treatment. The remaining 172 patients had been exposed to either inhaled or intestinal acting corticosteroid therapy. Mortality risk in non-users was 4.4% after 7 days and 15.6% after 1 year. This risk was doubled for corticosteroid users who filled their last prescription during the 90 days before admission, with mortality risks ranging from 14.2% after 7 days to 47.6% after 1 year. 1-year mortality risk was even higher for corticosteroid users with a first filled prescription ≤90 days before admission: 52.5%. Conclusions Corticosteroid use was associated with clearly increased mortality risk after perforated diverticular disease. Thus, use of corticosteroids should be regarded as an important clinical prognostic factor for mortality in patients with this condition.

Novel associations of bile acid diarrhoea with fatty liver disease and gallstones: a cohort retrospective analysis.

Abstract: Background Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods A cohort of patients with chronic diarrhoea who underwent 75 selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively. Additional clinical details available from the electronic patient record, including imaging, colonoscopy, chemistry and histopathology reports were used to calculate the prevalence of fatty liver disease, gallstones, colonic neoplasia and microscopic colitis, which was compared for BAD, the primary BAD subset and control patients with diarrhoea. Findings Of 578 patients, 303 (52%) had BAD, defined as a SeHCAT 7d retention value s =−0.19, p 31 ng/mL with imaging showing fatty liver (p 40 IU/L. In 176 subjects with gallbladder imaging, 27% had gallstones, 7% had a prior cholecystectomy and 34% either of these. The median SeHCAT values were lower in those with gallstones (3.8%, p Interpretation The diagnosis of BAD is associated with fatty liver disease and with gallstones. The reasons for these associations require further investigation into potential metabolic causes.

Barriers to care for chronic hepatitis C in the direct-acting antiviral era: a single-centre experience.

Abstract: Background Cure rates for chronic hepatitis C have improved dramatically with direct-acting antivirals (DAAs), but treatment barriers remain. We aimed to compare treatment initiation rates and barriers across both interferon-based and DAA-based eras. Methods We conducted a retrospective cohort study of all patients with chronic hepatitis C seen at an academic hepatology clinic from 1999 to 2016. Patients were identified to have chronic hepatitis C by the International Classification of Diseases, Ninth Revision codes, and the diagnosis was validated by chart review. Patients were excluded if they did not have at least one visit in hepatology clinic, were under 18 years old or had prior treatment with DAA therapy. Patients were placed in the DAA group if they were seen after 1 January 2014 and had not yet achieved virological cure with prior treatment. All others were considered in the interferon group. Results 3202 patients were included (interferon era: n=2688; DAA era: n=514). Despite higher rates of decompensated cirrhosis and medical comorbidities in the DAA era, treatment and sustained virological response rates increased significantly when compared with the interferon era (76.7% vs 22.3%, P Conclusions Despite higher rates of medical comorbidities in the DAA era, considerable treatment challenges remain including cost, loss to follow-up and ethnic disparities.

A Swedish national adoption study of risk of irritable bowel syndrome (IBS).

Abstract: Objectives Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. Methods We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964–2012 and the Swedish Outpatient Care Register for 2001–2012, and the Swedish Primary Healthcare register for 1989–2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h 2 (±SE) was also determined. Results The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. Conclusions The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees.

PCR detection of segmented filamentous bacteria in the terminal ileum of patients with ulcerative colitis

Abstract: Objectives Segmented filamentous bacteria (SFB) have been detected in a wide range of different animal. Recently, the presence of SFB-like bacteria was shown in biopsies of the terminal ileum and ileocecal valve of both patients with ulcerative colitis and control subjects. The aim of this study was to verify whether PCR methods could be used for the detection of SFB in biopsy of patients with ulcerative colitis and its relationships with the disease stage. Methods PCR methods were used to identify SFB in biopsies from the terminal ileum of patients with ulcerative colitis, showing that this approach represents a useful tool for the detection of SFB presence and analysis of the bacterial load. Results Our analysis detected SFB in all faecal samples of children at the time of weaning, and also show that putative SFB sequences are present in both patients with ulcerative colitis and control subjects. Results obtained using real-time quantitative PCR analysis confirm the presence of putative SFB sequences in samples from the terminal ileum of patients with ulcerative colitis and in control subjects. Conclusions The presence of putative SFB sequence in both patients with ulcerative colitis and control subject suggests that SFB cannot be considered as being uniquely associated with the disease. The second conclusion is that among the patients with ulcerative colitis, a tendency does exist for active disease samples to show higher SFB load, opening new perspectives about possible identification and pharmacological manipulation of SFB-mediated processes for new therapeutic strategy.

Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet

Abstract: Objectives Patients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD. Methods patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA–DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available. Results 48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA−DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p Conclusions Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.

Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis.

Abstract: Background Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. Aims To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. Methods In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. Results We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH Conclusions Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.

Neuropsychiatric performance and treatment of hepatitis C with direct-acting antivirals: a prospective study

Abstract: Background Since direct-acting antivirals (DAAs) have been approved for the treatment of hepatitis C virus (HCV) infection, a small series of patients with new-onset neuropsychiatric alterations have been referred to us. We therefore set out to study neuropsychiatric function in relation to DAAs prospectively. Methods Ten patients with cirrhosis and 12 post-liver transplant (post-LT) patients were enrolled. All underwent wake electroencephalography (EEG) and a neuropsychological evaluation (paper and pencil battery, simple/choice reaction times, working memory task) at baseline, at the end of treatment with DAAs and after 6 months. At the same time points, full blood count, liver/kidney function tests, quantitative HCV RNA, ammonia and immunosuppressant drug levels were obtained, as appropriate. Results Patients with cirrhosis were significantly older than post-LT patients (65±12 vs 55±7 years; P Conclusion Some degree of neuropsychiatric impairment was observed in relation to treatment with DAAs in patients with cirrhosis, but not in post-LT patients, suggesting that the former may be sensitive to mild DAA neurotoxicity.

Economic study of the value of expanding HCV treatment capacity in Germany

Abstract: Background Today9s highly efficacious, low-toxicity interferon-free treatment regimens for chronic hepatitis C virus (HCV) can cure most patients with HCV in 12–24 weeks. The aim of this study was to understand how the introduction of shorter duration treatment regimens for HCV will impact the capacity for treatment and value to society. Methods A Markov model of HCV transmission and progression was constructed, incorporating nationally representative data on HCV prevalence, incidence and progression; mortality, treatment costs, medical expenditures, employment probabilities and disability payments in Germany. The model was stratified by HCV genotype and exposure route (1-time healthcare exposure, injection drug use and sexual activity). Treatment scenarios were based on German treatment guidelines and projected treatment capacity. The impact of different treatment scenarios on disease transmission and prevalence, quality-adjusted life years (QALYs), treatment costs, medical expenditures, employment and disability expenditures was calculated. Results Depending on their adoption profile, new treatment regimens and protocols introduced over the next several years will increase HCV treatment capacity in Germany by 8–30%, reducing disease transmission and prevalence, increasing QALYs and adding €94–310 million in discounted social value (QALYs plus medical savings net of treatment costs) over a 30-year horizon. Additional social value in the form of higher employment and lower disability would also result. Conclusions The introduction of shorter HCV treatment regimens and the resulting increased treatment capacity in Germany would result in large gains to society by reducing disease transmission and prevalence, resulting in longer, healthier, more productive lives for current and future generations.

Comparison of outcomes between symptomatic and asymptomatic patients with colorectal cancer: a propensity score-matched analysis of surgical invasiveness, medical costs and oncological outcomes.

Abstract: Background and aims Whether asymptomatic patients with colorectal cancer (CRC) who are treated in hospitals show better outcomes than symptomatic patients with CRC still remains unknown. The aim of this study was to evaluate differences in clinical benefits following treatment in asymptomatic and symptomatic patients with CRC. Methods This study was a retrospective cohort analysis with data obtained from records. A cohort of 145 asymptomatic and 123 symptomatic patients who underwent CRC surgery between January 2009 and December 2011 was enrolled. To reduce bias in comparing outcomes, propensity score (PS) analysis was used for matching of patients in the symptomatic and asymptomatic groups based on clinicopathological factors. Surgical invasiveness, medical costs and oncological outcomes were examined by unadjusted and PS-matched analysis. Results Tumours in the symptomatic group were more often diagnosed in advanced stages compared with tumours in the asymptomatic group. Therefore, fewer symptomatic group patients underwent minimally invasive surgery. Short-term outcomes, including amount of blood loss, duration of postoperative hospital stay and perioperative medical costs, were significantly better in the asymptomatic group. Although overall survival was significantly better in the asymptomatic group, there was no significant difference between the groups when the patients were adjusted on the basis of PS. Conclusions Though this study was limited by the retrospective nature and small sample size, favourable outcomes in asymptomatic patients were due to the higher proportion of patients in this group who were diagnosed with CRC in earlier stages, due to participation in CRC screening programmes.