Response to: 'Full-spectrum (FUSE) versus standard forward-viewing colonoscopy in an organised colorectal cancer screening programme by Hassan et al
We presented retrospective data at Digestive Disease Week earlier this year describing more than 4000 patients who underwent screening colonoscopy at an ambulatory surgical centre, which transitioned from SFV to Fuse in... (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Nulsen, B., Lewis, B. Tags: PostScript Source Type: research

More viral mutants, less HBsAg clearance? One size may not fit all
Dear Sir, We read with great interest the article by Bayliss et al1 e-published in August 2016. HBV is a DNA virus and viral mutants develop during the course of persistent infection because of the spontaneous error of viral reverse transcription. Some of the viral mutants will be selected and become the predominant strains under the pressure of host immunity if they bear better replication fitness. Two common HBV mutants, mutations in precore stop codon (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A), have been shown to abolish or reduce the production of HBeAg, respectively, which contribute to disease progre...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Tseng, T.-C., Yang, H.-C., Kao, J.-H. Tags: PostScript Source Type: research

Prevention of progression from small to large varices: are we there yet? An updated meta-analysis
We read the article by Bhardwaj and coworkers1 with great interest. With their elegantly designed, randomised, single-blind, placebo-controlled study, Dr. Sarin and his research group have turned over a new leaf in the controversy on the effectiveness of non-selective beta blockers (NSBBs) in preventing the progression from small to large varices in patients who have not bled (table 1). Carvedilol has been shown to be more potent in decreasing portal pressure due to its additional anti-α1-adrenergic activity,2 and thus, achieves hemodynamic response even in non-responders to propranolol.3 Based on the stage-dependent...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Mandorfer, M., Peck-Radosavljevic, M., Reiberger, T. Tags: PostScript Source Type: research

Real-world risk score for hepatocellular carcinoma risk prediction in CHBV: a validation outside of Asia
With great interest we have read the recent paper by Poh et al1 suggesting the use of a routine parameter-based risk score for the development of hepatocellular carcinoma (HCC) in Asian patients with chronic HBV infection (CHBV). With an estimated 240 million people being chronically infected by HBV worldwide, CHBV is a major global health burden, putting these people at risk for the development of liver cirrhosis and HCC.2–4 It remains challenging to identify those patients with CHBV carrying a high risk for HCC development applying an easy to use, readily available and cost effective test system. Therefore risk pre...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Daheim, M., Lang, S., Goeser, T., Steffen, H.-M., Demir, M. Tags: PostScript Source Type: research

Characterisation of the faecal microbiota in Japanese patients with paediatric-onset primary sclerosing cholangitis
Dear Sir, Primary sclerosing cholangitis (PSC) is a liver disease often associated with IBD.1 Dysbiosis of the gut microbiota is implicated in PSC aetiology in adults,2–4 but less is known about paediatric-onset PSC. We analysed the faecal microbiota of 27 Japanese patients with paediatric-onset PSC as well as 16 age-matched patients with UC and 23 healthy controls (HCs) (see online S1) with pyrosequencing data of 16S rRNA gene V1-V2 region (accession #DRA004773). We assessed the influence of medications on the gut microbiota and found that salazosulfapyridine (SASP) treatment affected the microbiota structure with s...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Iwasawa, K., Suda, W., Tsunoda, T., Oikawa-Kawamoto, M., Umetsu, S., Inui, A., Fujisawa, T., Morita, H., Sogo, T., Hattori, M. Tags: Open access PostScript Source Type: research

GI highlights from the literature
Basic scienceHelicobacter pylori infection evades gastric acidity Bugaytsova JA, Björnham O, Chernov YA, et al. Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host Microbe 2017;21:376–389. Helicobacter pylori (HP) infects billions of people worldwide and is linked to both peptic ulcer disease and gastric cancer. HP colonises the gastric epithelium and its overlying mucus and is partially protected against luminal acidity by epithelial secretions, intrinsic urease production and chemotaxis. In addition, tight adherence to mucosal glycan receptors a...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

CRISPR/Cas9: at the cutting edge of hepatology
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome engineering has revolutionised biomedical science and we are standing on the cusp of medical transformation. The therapeutic potential of this technology is tremendous, however, its translation to the clinic will be challenging. In this article, we review recent progress using this genome editing technology and explore its potential uses in studying and treating diseases of the liver. We discuss the development of new research tools and animal models as well as potential clinical applications, strategies and challenges. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Pankowicz, F. P., Jarrett, K. E., Lagor, W. R., Bissig, K.-D. Tags: GUT Recent advances in basic science, Editor's choice Source Type: research

Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease
Conclusions Differential DNA methylation at the PPAR promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPAR could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Hardy, T., Zeybel, M., Day, C. P., Dipper, C., Masson, S., McPherson, S., Henderson, E., Tiniakos, D., White, S., French, J., Mann, D. A., Anstee, Q. M., Mann, J. Tags: Open access Hepatology Source Type: research

Role and therapeutic potential of vascular stem/progenitor cells in pathological neovascularisation during chronic portal hypertension
Conclusions These findings demonstrate that VSPC-derived neovessel growth (ie, vasculogenesis) and angiogenesis cooperatively stimulate mesenteric neovascularisation in PH and identify VSPC and CPEB4 as potential therapeutic targets. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Garcia-Pras, E., Gallego, J., Coch, L., Mejias, M., Fernandez-Miranda, G., Pardal, R., Bosch, J., Mendez, R., Fernandez, M. Tags: Hepatology Source Type: research

Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment
Conclusions Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Melgar-Lesmes, P., Balcells, M., Edelman, E. R. Tags: Hepatology Source Type: research

Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma
Objective Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Palbociclib, a well-tolerated and selective CDK4/6 inhibitor, has shown promising results in the treatment of retinoblastoma (RB1)-positive breast cancer. RB1 is rarely mutated in HCC, suggesting that palbociclib could potentially be used for HCC therapy. Here, we provide a comprehensive characterisation of the efficacy of palbociclib in multiple preclinical models of HCC. Design The effects of palbociclib on cell proliferation, cellular senescence and cell death were investigated in a panel of human liver cancer cell ...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Bollard, J., Miguela, V., Ruiz de Galarreta, M., Venkatesh, A., Bian, C. B., Roberto, M. P., Tovar, V., Sia, D., Molina-Sanchez, P., Nguyen, C. B., Nakagawa, S., Llovet, J. M., Hoshida, Y., Lujambio, A. Tags: Open access Hepatology Source Type: research

Pharmacological macrophage inhibition decreases metastasis formation in a genetic model of pancreatic cancer
Conclusions Pharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with impaired angiogenesis and reduced CD4+CD25+ T cell levels. Pharmacological targeting of infiltrating macrophages represents a promising novel tool for antimetastatic therapeutic approaches. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Griesmann, H., Drexel, C., Milosevic, N., Sipos, B., Rosendahl, J., Gress, T. M., Michl, P. Tags: Pancreas Source Type: research

Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers
Conclusions We showed that uc.158– is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Carotenuto, P., Fassan, M., Pandolfo, R., Lampis, A., Vicentini, C., Cascione, L., Paulus-Hock, V., Boulter, L., Guest, R., Quagliata, L., Hahne, J. C., Ridgway, R., Jamieson, T., Athineos, D., Veronese, A., Visone, R., Murgia, C., Ferrari, G., Guzzardo, Tags: Open access GI cancer Source Type: research

Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended?
Conclusions The diagnostic yield of FIT screening using a lowered positivity threshold in combination with an extended screening interval (up to 5 years) may be similar to conventional FIT strategies. This justifies and motivates further research steps in this direction. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Haug, U., Grobbee, E. J., Lansdorp-Vogelaar, I., Spaander, M. C. W., Kuipers, E. J. Tags: Colon Source Type: research

Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease
Conclusions Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Barbara, G., Scaioli, E., Barbaro, M. R., Biagi, E., Laghi, L., Cremon, C., Marasco, G., Colecchia, A., Picone, G., Salfi, N., Capozzi, F., Brigidi, P., Festi, D. Tags: Gut microbiota Source Type: research

Gallstone mimicry: a rare cause of abdominal pain
A previously fit and well 43-year-old male triathlete presented with severe central abdominal pain persisting for several hours. Three similar episodes in the past 18 months had spontaneously resolved. Prior investigations with abdominal ultrasound, upper and lower GI endoscopies had been unremarkable. On this presentation, the patient also had worsening malaise and fever at 40°C. He was fluid resuscitated and commenced on broad-spectrum antibiotics (intravenous piperacillin–tazobactam 4.5 g and 350 mg gentamicin). Initial biochemistry revealed absolute eosinophil count 0.56x109/L, asparate aminotransfe...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Singh, A., Smith, P. J., Cropley, I. M., Planche, K. L., Hamilton, M. I., Murray, C. D. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial
Objective To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. Design We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota compo...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: McIntosh, K., Reed, D. E., Schneider, T., Dang, F., Keshteli, A. H., De Palma, G., Madsen, K., Bercik, P., Vanner, S. Tags: Neurogastroenterology Source Type: research

Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)
Conclusion The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Zorzi, M., Senore, C., Da Re, F., Barca, A., Bonelli, L. A., Cannizzaro, R., de Pretis, G., Di Furia, L., Di Giulio, E., Mantellini, P., Naldoni, C., Sassatelli, R., Rex, D. K., Zappa, M., Hassan, C., the Equipe Working Group, Feliciangeli, Campari, Falci Tags: Endoscopy Source Type: research

Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview
Conclusions The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: IJspeert, J. E. G., Bevan, R., Senore, C., Kaminski, M. F., Kuipers, E. J., Mroz, A., Bessa, X., Cassoni, P., Hassan, C., Repici, A., Balaguer, F., Rees, C. J., Dekker, E. Tags: Endoscopy Source Type: research

Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome
Conclusion These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2 nanoparticles. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Ruiz, P. A., Moron, B., Becker, H. M., Lang, S., Atrott, K., Spalinger, M. R., Scharl, M., Wojtal, K. A., Fischbeck-Terhalle, A., Frey-Wagner, I., Hausmann, M., Kraemer, T., Rogler, G. Tags: Open access Inflammatory bowel disease Source Type: research

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux
Background and aims Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. Methods We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine,...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Robertson, E. V., Derakhshan, M. H., Wirz, A. A., Mitchell, D. R., Going, J. J., Kelman, A. W., Ballantyne, S. A., McColl, K. E. L. Tags: Oesophagus Source Type: research

Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis
Conclusions Our findings reveal for the first time that autophagy may function as a cytoprotective mechanism to maintain epithelial redox balance and homeostasis under EoE inflammation-associated stress, providing mechanistic insights into the role of autophagy in EoE pathogenesis. (Source: Gut)
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Whelan, K. A., Merves, J. F., Giroux, V., Tanaka, K., Guo, A., Chandramouleeswaran, P. M., Benitez, A. J., Dods, K., Que, J., Masterson, J. C., Fernando, S. D., Godwin, B. C., Klein-Szanto, A. J., Chikwava, K., Ruchelli, E. D., Hamilton, K. E., Muir, A. B Tags: Oesophagus Source Type: research

British Society of Gastroenterology position statement on serrated polyps in the colon and rectum
Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: East, J. E., Atkin, W. S., Bateman, A. C., Clark, S. K., Dolwani, S., Ket, S. N., Leedham, S. J., Phull, P. S., Rutter, M. D., Shepherd, N. A., Tomlinson, I., Rees, C. J. Tags: Open access Guidelines Source Type: research

CDK4/6 inhibition and sorafenib: a menage a deux in HCC therapy?
Hepatocytes are the foreign legionnaires in our body. They are exposed to various xenobiotics, which invigorates them and when transformed into malignant cells, renders them drug resistant. So far, treatment with the multikinase inhibitor sorafenib, which blocks Raf, vascular endothelial growth factor receptor and platelet-derived growth factor receptor signalling, is the only approved targeted therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib extends the average life expectancy of patients only 2.8 months over the placebo,1 which offers room for improvement. Unfortunately, several other drugs an...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Calvisi, D., Eferl, R. Tags: Commentary Source Type: research

Novel lncRNA T-UCR as a potential downstream driver of the Wnt/{beta}-catenin pathway in hepatobiliary carcinogenesis
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver tumours and their incidence is increasing worldwide. HCC commonly originates from chronic necroinflammation of liver parenchyma that promotes the malignant transformation of proliferating hepatocytes, whereas CCA arises from neoplastic biliary transformation. These types of cancer are frequently diagnosed in advanced stages compromising the limited therapeutic options mainly based on surgery. The molecular and cellular heterogeneity of these tumours, together with their rich tumour microenvironment, contribute to drug resistance...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Fernandez-Barrena, M. G., Perugorria, M. J., Banales, J. M. Tags: Commentary Source Type: research

Do diverticula provide a unique niche for microbiota which can lead to activation of the innate immune system?
As individuals living a Western lifestyle age, the prevalence of diverticulosis steadily rises reaching around 50% over the age of 75 years.1 While for most this is a harmless ageing change reflecting weakening of colonic connective tissue, around 30% suffer recurrent abdominal pain, often with diarrhoea,2 and 1–4% will be hospitalised with diverticulitis.3 As our population steadily ages this represents a substantial health burden, however, we know surprisingly little about the underlying mechanisms of this disease. Heritability of symptomatic diverticular disease is around 40%,4 however, studies of immigrants ...
Source: Gut - June 6, 2017 Category: Gastroenterology Authors: Spiller, R. C., Sloan, T. J. Tags: Commentary Source Type: research

Thank you to reviewers 2016
The Editor would like to publicly acknowledge the people listed below who served as reviewers on the journal during 2016. Without their efforts, the quality of the journal could not be sustained. Abel, Laurent Abraham, Clara Abrams, Julian Aden, Konrad Adolph, Timon Aghemo, Alessio Aghemo, Alessio Ahlenstiel, Golo Albano, Emanuele Alexandropoulos, Konstantina Alguel, Hana Allavena, Paola Allison, James Almeida, Maria Ines Aloman, Costica Altomonte, Jennifer Alvarez, Luis Anania, Frank Andersen, Jesper Andersen, Mads Hald Andrea, De Gottardi Andrisani, Ourania Angeli, Paolo Annese, Vito Annibale, Bruno Antoine, Daniel Appel...
Source: Gut - June 6, 2017 Category: Gastroenterology Tags: Reviewers Source Type: research

Clarifying misunderstandings and misinterpretations about proton pump inhibitor-responsive oesophageal eosinophilia
We appreciate the interest of Muir et al1 in our Position Paper on proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE).2 Their letter highlights the ongoing controversies related to PPI-REE, particularly regarding practical diagnostic concerns in paediatric patients. We would like to address several issues raised by the authors:When the clinical presentation is consistent with gastro-oesophageal reflux disease (GORD), an empiric trial of PPI therapy is always appropriate. Teenagers and adults with dysphagia, however, should undergo an endoscopic procedure, because dysphagia is a red-flag symptom. In adult p...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Molina-Infante, J., Hirano, I., Spechler, S. J., on behalf of the PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS) Tags: PostScript Source Type: research

Percutaneous cooled-probe microwave versus radiofrequency ablation in early-stage hepatocellular carcinoma: a phase III randomised controlled trial
We read with interest the article by Bruix et al1 on currently available treatment options for hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) is now the first-line technique for HCC ablation. RFA produces tumour necrosis in situ through temperature modification. Compared with RFA, microwave ablation (MWA) is one relatively recent advancement of thermoablative technology, which shows multiple theoretical advantages over RFA.2–4 We wish to report the results of a phase III randomised controlled trial (RCT) by comparing ultrasound-guided percutaneous cooled-probe MWA and RFA in ≤5 cm HCC (NCT 0253...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Yu, J., Yu, X.-l., Han, Z.-y., Cheng, Z.-g., Liu, F.-y., Zhai, H.-y., Mu, M.-j., Liu, Y.-m., Liang, P. Tags: Open access PostScript Source Type: research

Lack of evidence for germline RNF43 mutations in patients with serrated polyposis syndrome from a large multinational study
Serrated polyposis syndrome (SPS) is characterised by the occurrence of multiple serrated polyps in the large bowel. Defined clinically by the 2010 revised WHO, SPS is associated with an increased risk of colorectal cancer (CRC) for affected individuals and their first-degree relatives. Yan et al1 recently reported their findings from whole-exome sequencing (WES) of six individuals with SPS from four families, identifying a single family carrying a germline likely pathogenic variant in RNF43 (c.953-1 G>A, c.953_954delAG, p.E318fs). In this family, six carriers were identified, five of whom met the WHO criteria for SPS. ...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Buchanan, D. D., Clendenning, M., Zhuoer, L., Stewart, J. R., Joseland, S., Woodall, S., Arnold, J., Semotiuk, K., Aronson, M., Holter, S., Gallinger, S., Jenkins, M. A., Sweet, K., Macrae, F. A., Winship, I. M., Parry, S., Rosty, C., on behalf of the Gen Tags: PostScript Source Type: research

The {gamma}-glutamyl transpeptidase to platelet ratio (GPR) in HBV patients: just adding up?
We read with interest the article by Lemoine et al evaluating routine tests as non-invasive markers of fibrosis in patients with chronic hepatitis B (CHB).1 The -glutamyl transpeptidase to platelet ratio (GPR) has been proposed as a new fibrosis test, allegedly more accurate than classical biomarkers like the Aspartate Aminotransferase to Platelet Ratio Index (APRI) and FIB-4 in African cohorts. Therefore, we performed a validation analysis of GPR in 147 patients with untreated CHB from two Brazilian reference centres. The mean age was 40.6±13.7 years and 68% were male. Hepatitis B e antigen (HBeAg) was positiv...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Schiavon, L. L., Narciso-Schiavon, J. L., Ferraz, M. L. G., Silva, A. E. B., Carvalho-Filho, R. J. Tags: PostScript Source Type: research

Dyspepsia and the microbiome: time to focus on the small intestine
We note with interest two recent publications in Gut regarding alterations to the gut microbiome in individuals on proton pump inhibitor (PPI) therapy.1 2 With PPI use, both studies observed an increase in oral bacteria in the stool. These changes overlap with those described in patients with cirrhosis of the liver.3 However, very little is known about the impact of this dysbiosis over the length of the GI tract, and how it may link to gut function. While the data from both Jackson et al1 and Imhann et al2 are demonstrative of a shift towards oral-associated bacteria, it is important to note that many of these bacteria hav...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Zhong, L., Shanahan, E. R., Raj, A., Koloski, N. A., Fletcher, L., Morrison, M., Walker, M. M., Talley, N. J., Holtmann, G. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the authors use singlemolecule fluorescence in situ hybridisation and single-cell RNA sequencing (scRNA-seq) to define exhaustively the zonation profiles of all liver genes in mice. Using a panel of six zonally distributed genes (Glul, Cyp2e1, Ass1, Asl, Alb, Cyp2f2), they defined a ‘spatial barcode’, whereby the relative expression of these zonal genes could infer the location of a given cell within one of nine lobule layers between the central vein and portal node. They proceeded to perform scRNA-seq on freshly isolated hepatocytes and used expression levels of the spatial barcode genes to assi...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Drug-induced liver injury: recent advances in diagnosis and risk assessment
Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. New emerging biomarkers which could be useful in asses...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Kullak-Ublick, G. A., Andrade, R. J., Merz, M., End, P., Benesic, A., Gerbes, A. L., Aithal, G. P. Tags: GUT Recent advances in clinical practice, Open access Source Type: research

Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory ‘milieu’ initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Adams, L. A., Anstee, Q. M., Tilg, H., Targher, G. Tags: GUT Recent advances in clinical practice Source Type: research

Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury
Conclusions During liver fibrosis, the increase in OPN induces HMGB1, which acts as a downstream alarmin driving collagen-I synthesis in HSCs. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Arriazu, E., Ge, X., Leung, T.-M., Magdaleno, F., Lopategi, A., Lu, Y., Kitamura, N., Urtasun, R., Theise, N., Antoine, D. J., Nieto, N. Tags: Cirrhosis Hepatology Source Type: research

Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer
Objective Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. Design We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Bao, Y., Prescott, J., Yuan, C., Zhang, M., Kraft, P., Babic, A., Morales-Oyarvide, V., Qian, Z. R., Buring, J. E., Cochrane, B. B., Gaziano, J. M., Giovannucci, E. L., Manson, J. E., Ng, K., Ogino, S., Rohan, T. E., Sesso, H. D., Stampfer, M. J., Fuchs, Tags: Pancreas and biliary tract, Editor's choice, Pancreatic cancer Source Type: research

Inhibition of RAF1 kinase activity restores apicobasal polarity and impairs tumour growth in human colorectal cancer
Conclusions RAF1 plays a critical role in maintaining the transformed phenotype of CRC cells, including those with mutated KRAS. The effects of RAF1 are kinase-dependent, but MEK-independent. Despite the lack of activating mutations in RAF1, its kinase domain is an attractive therapeutic target for CRC. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Borovski, T., Vellinga, T. T., Laoukili, J., Santo, E. E., Fatrai, S., van Schelven, S., Verheem, A., Marvin, D. L., Ubink, I., Borel Rinkes, I. H. M., Kranenburg, O. Tags: Colon cancer Source Type: research

RSPO3 expands intestinal stem cell and niche compartments and drives tumorigenesis
Conclusions We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis. This establishes RSPO3 as a potent driver of intestinal cancer and proposes RSPO3 as a candidate target for therapy in patients with colorectal cancer harbouring RSPO3 fusions. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Hilkens, J., Timmer, N. C., Boer, M., Ikink, G. J., Schewe, M., Sacchetti, A., Koppens, M. A. J., Song, J.-Y., Bakker, E. R. M. Tags: Open access GI cancer Source Type: research

{alpha}-Conotoxin Vc1.1 inhibits human dorsal root ganglion neuroexcitability and mouse colonic nociception via GABAB receptors
Conclusions Vc1.1-mediated activation of GABABR is a novel mechanism for reducing the excitability of human DRG neurons. Vc1.1-induced activation of GABABR on the peripheral endings of colonic afferents reduces nociceptive signalling. The enhanced antinociceptive actions of Vc1.1 during CVH suggest it is a novel candidate for the treatment for CVP. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Castro, J., Harrington, A. M., Garcia-Caraballo, S., Maddern, J., Grundy, L., Zhang, J., Page, G., Miller, P. E., Craik, D. J., Adams, D. J., Brierley, S. M. Tags: Open access Neurogastroenterology Source Type: research

The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review
Conclusions The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Sperber, A. D., Dumitrascu, D., Fukudo, S., Gerson, C., Ghoshal, U. C., Gwee, K. A., Hungin, A. P. S., Kang, J.-Y., Minhu, C., Schmulson, M., Bolotin, A., Friger, M., Freud, T., Whitehead, W. Tags: Neurogastroenterology Source Type: research

A rare cause of GI bleeding in a 56-year-old man
A 56-year-old man, with a known history of diabetes for 1 year, presented with a 5-day history of melena that was associated with one episode of haematemesis. One month prior, he had completed a course of oral amoxicillin for a dental infection that occurred after a tooth extraction. The only other significant past medical problem was hypertension for 10 years. Physical examination only showed pallor and abdominal examination was normal. Laboratory investigations revealed haemoglobin level of 8.4 g/dL and HbA1C of 7.8%. His upper GI endoscopy showed a diffuse irregular friable exudative ulcerative lesio...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Lin, P.-Y., Tang, J.-H., Chang, C.-C. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease
Conclusions NPC1 confers increased risk of early-onset severe CD. Our data support the concept that genetic defects at different checkpoints of selective autophagy cause a shared outcome of CD-like immunopathology linking monogenic and polygenic forms of IBD. Muramyl dipeptide-driven cytokine responses and antibacterial autophagy induction are parallel and independent signalling cascades downstream of the NOD2-RIPK2-XIAP complex. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Schwerd, T., Pandey, S., Yang, H.-T., Bagola, K., Jameson, E., Jung, J., Lachmann, R. H., Shah, N., Patel, S. Y., Booth, C., Runz, H., Düker, G., Bettels, R., Rohrbach, M., Kugathasan, S., Chapel, H., Keshav, S., Elkadri, A., Platt, N., Muise, A. Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials
Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, ...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Panes, J., Sandborn, W. J., Schreiber, S., Sands, B. E., Vermeire, S., D'Haens, G., Panaccione, R., Higgins, P. D. R., Colombel, J.-F., Feagan, B. G., Chan, G., Moscariello, M., Wang, W., Niezychowski, W., Marren, A., Healey, P., Maller, E. Tags: Open access Inflammatory bowel disease Source Type: research

Fungal microbiota dysbiosis in IBD
Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Sokol, H., Leducq, V., Aschard, H., Pham, H.-P., Jegou, S., Landman, C., Cohen, D., Liguori, G., Bourrier, A., Nion-Larmurier, I., Cosnes, J., Seksik, P., Langella, P., Skurnik, D., Richard, M. L., Beaugerie, L. Tags: Open access Inflammatory bowel disease Source Type: research

The effect of heritability and host genetics on the gut microbiota and metabolic syndrome
Conclusions Our results suggest that an altered microbiota composition mediated by a specific host genotype can contribute to the development of MetS. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Lim, M. Y., You, H. J., Yoon, H. S., Kwon, B., Lee, J. Y., Lee, S., Song, Y.-M., Lee, K., Sung, J., Ko, G. Tags: Gut microbiota Source Type: research

The learning curve to achieve satisfactory completion rates in upper GI endoscopy: an analysis of a national training database
Conclusions There are limited published data on the OGD learning curve. This is the largest study to date analysing the learning curve for competency acquisition. The JAG competency requirement for 200 procedures appears appropriate. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Ward, S. T., Hancox, A., Mohammed, M. A., Ismail, T., Griffiths, E. A., Valori, R., Dunckley, P. Tags: Endoscopy Source Type: research

Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids
Conclusions Gastric carcinoids require threshold levels of hypergastrinemia, which modulates p27Kip1 cellular location and stability. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Sundaresan, S., Kang, A. J., Hayes, M. M., Choi, E.-Y. K., Merchant, J. L. Tags: Gastrointestinal hormones, Stomach and duodenum Source Type: research

Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis
Conclusions Notch signalling is required to maintain gastric antral stem cells. Notch1 and Notch2 are the primary Notch receptors regulating epithelial cell homoeostasis in mouse and human stomach. (Source: Gut)
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Gifford, G. B., Demitrack, E. S., Keeley, T. M., Tam, A., La Cunza, N., Dedhia, P. H., Spence, J. R., Simeone, D. M., Saotome, I., Louvi, A., Siebel, C. W., Samuelson, L. C. Tags: Stomach and duodenum Source Type: research

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care
The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Brooks, A. J., Smith, P. J., Cohen, R., Collins, P., Douds, A., Forbes, V., Gaya, D. R., Johnston, B. T., McKiernan, P. J., Murray, C. D., Sebastian, S., Smith, M., Whitley, L., Williams, L., Russell, R. K., McCartney, S. A., Lindsay, J. O. Tags: Guidelines Source Type: research