PGAM5: a new player in immune-mediated liver injury
Mechanisms of cell death are critical in any pathophysiology and hence have been extensively investigated in a number of different organ systems. Initially, the term ‘programmed cell death’ was exclusively applied to apoptosis, where molecular mediators and signalling pathways involved in the process were relatively well characterised. The other form of cell death, namely necrosis, was considered to be an uncontrolled process, where catastrophic events within the cell resulted in a rupture of the plasma membrane with release of cell contents. However, this paradigm has been rapidly evolving as new pathways and ...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Ramachandran, A., Jaeschke, H. Tags: Commentary Source Type: research

A small RNA in neutrophils protects against acute-on-chronic alcoholic liver injury
Alcoholic liver disease (ALD) is a major cause of chronic liver injury worldwide.1 2 Clinically, jaundice and liver failure are hallmark presentations of patients with severe alcoholic hepatitis (AH) who typically have been drinking up to the time of admission or have stopped drinking within 4–6 weeks of their presentation of symptoms. The liver histology of AH has features of steatohepatitis, hepatic neutrophil infiltration, cholestasis and florid inflammation.3 Among patients with ALD, liver-related mortality is much higher in patients with AH than those with only simple steatosis.3 Current recommended treatme...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Wang, S., Ding, W.-X. Tags: Commentary Source Type: research

Colorectal cancer cells use the negative feedback regulators of WNT signalling to activate epithelial-mesenchymal transition pathways
Epithelial–mesenchymal transition (EMT) is a reversible embryonic genetic programme pathologically activated in cancer. The EMT phenomenon has been considered in the context of distant metastases in different carcinoma types including colorectal cancer (CRC). The hallmark of EMT is dissolution of epithelial intercellular junctions and global reorganisation of the cytoskeleton leading to the loss of epithelial features and gain of mesenchymal morphology. EMT programmes are controlled by several groups of embryonic transcription factors (EMT-TFs), of which TWIST1, SNAIL1, ZEB1 and ZEB2 expression correlated with poor p...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Tulchinsky, E. Tags: Commentary Source Type: research

Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury
Dear Editor, We read with great interest the elegant work of Sayed et al,1 which established a mouse model for chronic hepatitis E virus (HEV) infections. The study showed that mice with humanised livers could be infected with both HEV-1 and HEV-3 and develop a chronic viral infection. The establishment of this model meets the urgent need for a research animal model to study chronic hepatitis E infection as increasing cases of such infections have been reported in immunocompromised patients.2 We have recently reported on a chronic hepatitis E case caused by HEV-4 in a woman with nephritic syndrome.3 HEV RNA and antigen wer...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Wang, L., Xia, J., Wang, L., Wang, Y. Tags: PostScript Source Type: research

Author response to letter: colonic stenting in patients on P2Y12 receptor antagonists and direct oral anticoagulants--are current BSG/ESGE guidelines practical?
We thank the authors for their interest in the recently published British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy (ESGE) guidelines on endoscopy in patients on antiplatelet or anticoagulant therapy.1 As stated in the summary of recommendations, these guidelines refer to the management of elective endoscopic procedures. For elective palliative colonic stenting, there is often adequate time to discontinue antithrombotic therapy, including P2Y12 antagonists. In an emergency situation, we agree with the authors that the balance of risk between haemorrhage due to stenting versus death due ...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Veitch, A., Dumonceau, J.-M. Tags: PostScript Source Type: research

Stool frequency is associated with gut microbiota composition
We examined the association between gut microbiota and stool frequency in the Population-based Colonoscopy study, a general population-based cohort from Stockholm, Sweden, previously described in detail.5 Sixty-nine individuals (21 males and... (Source: Gut)
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Hadizadeh, F., Walter, S., Belheouane, M., Bonfiglio, F., Heinsen, F.-A., Andreasson, A., Agreus, L., Engstrand, L., Baines, J. F., Rafter, J., Franke, A., D'Amato, M. Tags: PostScript Source Type: research

Sequential shear-wave elastography of liver and spleen rules out clinically significant portal hypertension in compensated advanced chronic liver disease
With interest we read the letter entitled ‘Ruling in and ruling out with elastography in compensated advanced chronic liver disease’ by Agustin et al1 to our study ‘Algorithm to rule-out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multi-centre study’.2 Indeed, we would like to thank our colleagues for their interest in our study and deciphering the strengths and weaknesses of this study. Besides acknowledging the merits of the study, the colleagues commented on the selection of patients regarding severity and aetiology of advanced c...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Jansen, C., Bogs, C., Krag, A., Francque, S., Trebicka, J. Tags: PostScript Source Type: research

Reply to letter to the editor of Gut by Dickson and Cox
Dear editor, We are thankful for the letter of Drs Dickson and Cox in response to our paper on the effect of the intestinal microbiota on host responses during pneumococcal pneumonia.1 We do agree that we cannot rule out that the antibiotics we used in our experiments could have influenced the microbiota in the airways and we do underwrite the importance of studying local host–microbe interactions within the respiratory tract during pneumonia. However, some points need to be addressed. The relative importance of the microbiota of the lower airways, the area where alveolar macrophages reside, is a matter of debate. A ...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Lankelma, J. M., Schuijt, T. J., Wiersinga, W. J. Tags: PostScript Source Type: research

The reduced chance of a live birth in women with IBD receiving assisted reproduction is due to a failure to achieve a clinical pregnancy
We recently reported that for women with UC receiving assisted reproductive technology (ART) treatment, the chance of a live birth after each embryo transfer cycle decreased significantly. In women with Crohn's disease (CD), the chance of a live birth after each embryo transfer cycle also decreased but was not significant in the fully adjusted regression model.1 In our study, we chose the outcome live birth because it was the most important clinical outcome for patients with UC and CD undergoing ART. After demonstrating the negative effects of UC and CD on chances of live birth, we wish to update our readers by exploring w...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Friedman, S., Larsen, P. V., Fedder, J., Norgard, B. M. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceMutation burden in cancer cells Blokzijl F, de Ligt J, Jager M, et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 2016;538:260–4. In cancer, stem cells are thought to be the primary target for genetic defects due to the fact that they live far longer than any differentiated cells; however, no accurate estimation of the mutation rate in human tissue stem cells (particularly colon, small intestine and liver) has been established. Here, the authors have generated 45 organoid cultures, from 19 donors ranging in age from 3 to 87 years, from stem cells extracted fr...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Don't mistake it as a polyp!
CLINICAL PRESENTATION A middle-aged woman first presented with vague abdominal symptoms of bloatedness and change in bowel habits. Physical examination was otherwise unremarkable. A colonoscopic evaluation was performed, which demonstrated a possible appendiceal mass (figure 1). A CT scan of the abdomen and pelvis was performed, which confirmed the bulky appendix (figure 2). In view of the indeterminate nature of the lesion and inability to rule out an underlying neoplastic process, the patient was counselled for surgical resection of the appendix, with the possibility of a limited right hemicolectomy. Intraoperatively, th...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Tian-Zhi, L., Leong Qi Hui, F., Tan, K.-K. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Acute-on-chronic liver failure: an update
Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%–50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment fail...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Hernaez, R., Sola, E., Moreau, R., Gines, P. Tags: GUT Recent advances in clinical practice, Open access Source Type: research

Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma
Objective Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance. Design HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative s...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Tovar, V., Cornella, H., Moeini, A., Vidal, S., Hoshida, Y., Sia, D., Peix, J., Cabellos, L., Alsinet, C., Torrecilla, S., Martinez-Quetglas, I., Lozano, J. J., Desbois-Mouthon, C., Sole, M., Domingo-Domenech, J., Villanueva, A., Llovet, J. M. Tags: Hepatic cancer Hepatology Source Type: research

Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis
Conclusions In severe liver fibrosis and cirrhosis, failure to control bacterial infection is caused by augmented IFN and IL-10 expression that incapacitates antibacterial immunity of myeloid cells. Targeted interference with the immune regulatory host factors IL-10 and IFN reconstitutes antibacterial immunity and may be used as therapeutic strategy to control bacterial infections in patients with liver cirrhosis. (Source: Gut)
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Hackstein, C.-P., Assmus, L. M., Welz, M., Klein, S., Schwandt, T., Schultze, J., Förster, I., Gondorf, F., Beyer, M., Kroy, D., Kurts, C., Trebicka, J., Kastenmüller, W., Knolle, P. A., Abdullah, Z. Tags: Cirrhosis Hepatology Source Type: research

Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis
Objective To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians’ recommendation, patient personal choice or comorbidities precluding surgery. Methods In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific s...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Crippa, S., Bassi, C., Salvia, R., Malleo, G., Marchegiani, G., Rebours, V., Levy, P., Partelli, S., Suleiman, S. L., Banks, P. A., Ahmed, N., Chari, S. T., Fernandez-del Castillo, C., Falconi, M. Tags: Pancreas and biliary tract Source Type: research

Risk stratification of individuals with low-risk colorectal adenomas using clinical characteristics: a pooled analysis
Objective For individuals with 1–2 small (
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Gupta, S., Jacobs, E. T., Baron, J. A., Lieberman, D. A., Murphy, G., Ladabaum, U., Cross, A. J., Jover, R., Liu, L., Martinez, M. E. Tags: Endoscopy, Colon cancer Source Type: research

Adenoma detection with Endocuff colonoscopy versus conventional colonoscopy: a multicentre randomised controlled trial
Background and aims Colonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC). Methods We performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: van Doorn, S., van der Vlugt, M., Depla, A., Wientjes, C., Mallant-Hent, R., Siersema, P., Tytgat, K., Tuynman, H., Kuiken, S., Houben, G., Stokkers, P., Moons, L., Bossuyt, P., Fockens, P., Mundt, M., Dekker, E. Tags: Endoscopy, Colon cancer Source Type: research

Microbiota-induced obesity requires farnesoid X receptor
Conclusions Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition. (Source: Gut)
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Parseus, A., Sommer, N., Sommer, F., Caesar, R., Molinaro, A., Stahlman, M., Greiner, T. U., Perkins, R., Bäckhed, F. Tags: Open access Gut microbiota Source Type: research

Efficacy of psychotropic drugs in functional dyspepsia: systematic review and meta-analysis
Conclusions Psychotropic drugs may be an effective treatment for FD, but the effect appears to be limited to antipsychotics and tricyclic antidepressants with fewer trials for other agents, meaning that firm conclusions for efficacy cannot be made. More data from high quality RCTs are required to support their use in the treatment of FD. (Source: Gut)
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Ford, A. C., Luthra, P., Tack, J., Boeckxstaens, G. E., Moayyedi, P., Talley, N. J. Tags: Dyspepsia Neurogastroenterology Source Type: research

The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis
Conclusions Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage. (Source: Gut)
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Fisher, O. M., Lord, S. J., Falkenback, D., Clemons, N. J., Eslick, G. D., Lord, R. V. Tags: Open access, Oesophageal cancer Oesophagus Source Type: research

Gut microbiota and Toll-like receptors set the stage for cytokine-mediated failure of antibacterial responses in the fibrotic liver
The gut–liver axis is increasingly recognised as a key contributor to chronic liver disease. A failing gut barrier contributes to increased bacterial translocation, which results in an elevated risk of bacterial infection and a chronic inflammatory state that may promote the progression of chronic liver disease and the development of long-term complications such as fibrosis and HCC.1 2 The most important clinical consequence of increased translocation is acute bacterial infection, a common cause of hospital admissions and a major contributor to morbidity and mortality in patients with cirrhosis. Moreover, bacterial i...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Kuntzen, C., Schwabe, R. F. Tags: Commentary Source Type: research

Preventing disease relapses in autoimmune pancreatitis with maintenance steroids: are we there yet?
Autoimmune pancreatitis (AIP) is a fibro-inflammatory disease, which has defining histopathology and is characterised by a dramatic response to steroid treatment.1 Type 1 AIP describes the pancreatic manifestation of a multiorgan syndrome, currently referred to as IgG4-related disease and is frequently associated with an elevated serum IgG4 antibody level.2 This is a chronic disease with relapses occurring in 30–50% of patients within 3 years of disease onset.3 4 Published data suggest that low-dose maintenance steroids may decrease the risk for future disease relapse; however, this has not been demonstrated in ...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Hart, P. A., Chari, S. T. Tags: Commentary Source Type: research

Building pancreatic organoids to aid drug development
Comment on: gutjnl-2016-312423 ‘Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling’ Much of our understanding of human diseases comes from the study of model systems such as cell lines. Cell lines are derived from cells that have obtained the property to proliferate indefinitely, often by immortalisation or isolation from cancerous tissues. They have the great advantage that they are easy to work with and can be kept in culture almost endlessly. The disadvantage is that they have lost the genetic signature of healthy pr...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Wills, E. S., Drenth, J. P. H. Tags: Commentary Source Type: research

Ethics and hepatitis B cure research
Recent scientific advances, including the development of curative therapies for HCV and the establishment of global cure initiatives for HIV, have led to international calls seeking a cure for chronic infection with HBV.1 2 Over 240 million people live with chronic HBV, resulting in up to 780 000 deaths annually due to hepatic fibrosis/cirrhosis and hepatocellular carcinoma (HCC).3 4 Persons chronically infected with HBV who do not receive treatment have a lifelong risk of developing HCC, the third most common cause of disease globally.5–7 Along with scaled-up approaches to preventing and treating chronic HBV in...
Source: Gut - February 14, 2017 Category: Gastroenterology Authors: Sugarman, J., Revill, P., Zoulim, F., Yazdanpanah, Y., Janssen, H. L. A., Lim, S. G., Lewin, S. R. Tags: Hepatic cancer Leading article Source Type: research

Reply to the letter by Dr Graham concerning ethical and interpretation issues with vonoprazan-containing H. pylori eradication therapy
We thank Dr Graham for his interest in our article.1 2 In Japan, 7 days administration of PPI+amoxicillin+clarithromycin is standard treatment for Helicobacter pylori eradication3 and is the only approved treatment as first-line therapy in Japan. Therefore, there is no ethical issue in increasing sample size to match the current eradication rate. In a blinded interim analysis, the overall eradication rate was 81.6%, which was a lower rate than 90% that we used in the initial sample size estimation. However, at the time, it was difficult to determine whether this was due to a difference between a high eradication rate ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Murakami, K., Sakurai, Y., Shiino, M., Funao, N., Nishimura, A., Asaka, M. Tags: PostScript Source Type: research

The gut-adherent microbiota of PSC-IBD is distinct to that of IBD
Primary sclerosing cholangitis–IBD (PSC–IBD) is an inflammatory autoimmune hepato–biliary–enteric disease in which it is predicted that gut microbiota have potential pathophysiological effects, relevant to disease initiation and outcome. The recent article by Kummen et al1 who reported that the gut microbiota in PSC is distinct compared with those from healthy controls and patients with UC without liver disease, is therefore of interest. However, it remains unclear if these alterations in the gut microbiota are a cause or an effect of liver disease, and there remains a challenging task to link dysbi...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Quraishi, M. N., Sergeant, M., Kay, G., Iqbal, T., Chan, J., Constantinidou, C., Trivedi, P., Ferguson, J., Adams, D. H., Pallen, M., Hirschfield, G. M. Tags: PostScript Source Type: research

Gut microbiota and protection from pneumococcal pneumonia
Dear Editor, We read with interest the work by Schuijt et al1 reporting that sustained treatment with broad-spectrum antibiotics increases the susceptibility of mice to pneumococcal pneumonia, an effect that is reversed via faecal microbiota transplantation (FMT). Yet we question the authors' confidence that this effect is entirely attributable to alterations in gut microbiota. Antibiotic therapy, as used by the authors, alters the microbiota of the upper and lower respiratory tract.2 3 The authors used FMT to determine that the protective effect was due to gut microbiota, yet their protocol for FMT—oral gavage with ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Dickson, R. P., Cox, M. J. Tags: PostScript Source Type: research

Vonoprazan Helicobacter pylori eradication therapy: ethical and interpretation issues
We read with interest the important study on vonoprazan in Helicobacter pylori eradication therapy.1 Vonoprazan likely represents a significant advance in antisecretory and H. pylori eradication therapy. Despite being technically well done, several issues related to study conduct and interpretation remain. Their sample size was based on 90% success with lansoprazole, which has not been achieved in Japan for several decades. When the cure rates proved to be lower, the sample size was increased to ‘maintain the statistical power of the study’. We question whether this was ethical. It is generally considered uneth...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Graham, D. Y. Tags: PostScript Source Type: research

Colonic stenting in patients on P2Y12 receptor antagonists and direct oral anticoagulants: are current BSG/ESGE guidelines practical?
We thank the British Society of Gastroenterology and the European Society of Gastrointestinal Endoscopy for updating guidelines relating to endoscopy in patients on antiplatelets or anticoagulation therapy.1 However, we wish to raise two important issues. First, this guideline recommends deferring colonic stent placement in patients on P2Y12 receptor antagonists until it is discontinued for at least 5 days. However, malignant colonic obstruction (unlike oesophageal or pyloric obstruction) is an emergency, which if not dealt with immediately could potentially result in serious adverse events. Self-expanding mesh stent ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Murugesan, S. V. M., Hendrickse, M. T. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceMLKL-mediated hepatocyte necrosis in immune liver disease—not all hepatocyte death is the same Gunther C, He GW, Kremer AE, et al. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis. J Clin Invest 2016;126:4346–60. Hepatocellular death has long been associated with both acute and chronic liver injury. Mechanisms of cell death can extend beyond apoptosis and necrosis and vary greatly, with pathways such as necroptosis (programmed cell necrosis) now well described. A more detailed dissection of the pathways involved in hepatocellular death in dif...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD?
The genetics of isolated colonic Crohn's disease place it approximately midway between Crohn's disease with small intestinal involvement and UC, making a case for considering it as a separate condition. We have therefore systematically reviewed its epidemiology, pathophysiology and treatment. Key findings include a higher incidence in females (65%) and older average age at presentation than Crohn's disease at other sites, a mucosa-associated microbiota between that found in ileal Crohn's disease and UC, no response to mesalazine, but possibly better response to antitumour necrosis factor than Crohn's disease at other sites...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Subramanian, S., Ekbom, A., Rhodes, J. M. Tags: Crohn's disease, GUT Recent advances in clinical practice, Editor's choice Source Type: research

STAT4-associated natural killer cell tolerance following liver transplantation
Objective Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. Design Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. Results NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Jamil, K. M., Hydes, T. J., Cheent, K. S., Cassidy, S. A., Traherne, J. A., Jayaraman, J., Trowsdale, J., Alexander, G. J., Little, A.-M., McFarlane, H., Heneghan, M. A., Purbhoo, M. A., Khakoo, S. I. Tags: Open access Hepatology Source Type: research

Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma
Conclusions The close proximity of tumour-infiltrating T cells and B cells indicates a functional interaction between them that is linked to an enhanced local immune activation and contributes to better prognosis for patients with HCC. (Source: Gut)
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Garnelo, M., Tan, A., Her, Z., Yeong, J., Lim, C. J., Chen, J., Lim, K. H., Weber, A., Chow, P., Chung, A., Ooi, L. L. P., Toh, H. C., Heikenwalder, M., Ng, I. O. L., Nardin, A., Chen, Q., Abastado, J.-P., Chew, V. Tags: Open access, Hepatic cancer Hepatology Source Type: research

Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study
This study was conducted to evaluate the association between NAFLD and the progression of coronary atherosclerosis. Methods This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD), liver disease or cancer at baseline who participated in a repeated regular health screening examination between 2004 and 2013. Fatty liver was diagnosed by ultrasound based on standard criteria, including parenchymal brightness, liver-to-kidney contrast, deep beam attenuation and bright vessel walls. Progression of coronary artery calcium (CAC) scores was measured using multidetector CT ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Sinn, D. H., Kang, D., Chang, Y., Ryu, S., Gu, S., Kim, H., Seong, D., Cho, S. J., Yi, B.-K., Park, H.-D., Paik, S. W., Song, Y. B., Lazo, M., Lima, J. A. C., Guallar, E., Cho, J., Gwak, G.-Y. Tags: Nonalcoholic steatosis Hepatology Source Type: research

When banding fails; investigation hails
Clinical presentation A 67-year-old man presented to our centre 5 years ago with a short history of jaundice and weight loss. A diagnosis of autoimmune hepatitis was made following laboratory investigations, imaging and a trans-jugular liver (TJ) biopsy. He was treated with prednisolone and azathioprine, which resulted in normalisation of his transaminases and bilirubin. Four years later, he was diagnosed with cirrhosis (Childs class A) based on clinical, biochemical and radiological parameters. He underwent a screening endoscopy, which revealed grade III oesophageal varices with multiple red signs and was started on ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Arnold, F., Patch, D., Yu, D., Westbrook, R. H. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release
Objective Caffeine reduces toxic Ca2+ signals in pancreatic acinar cells via inhibition of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated signalling, but effects of other xanthines have not been evaluated, nor effects of xanthines on experimental acute pancreatitis (AP). We have determined effects of caffeine and its xanthine metabolites on pancreatic acinar IP3R-mediated Ca2+ signalling and experimental AP. Design Isolated pancreatic acinar cells were exposed to secretagogues, uncaged IP3 or toxins that induce AP and effects of xanthines, non-xanthine phosphodiesterase (PDE) inhibitors and cyclic adenosine monopho...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Huang, W., Cane, M. C., Mukherjee, R., Szatmary, P., Zhang, X., Elliott, V., Ouyang, Y., Chvanov, M., Latawiec, D., Wen, L., Booth, D. M., Haynes, A. C., Petersen, O. H., Tepikin, A. V., Criddle, D. N., Sutton, R. Tags: Pancreas and biliary tract, Pancreatitis, Open access Source Type: research

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program
Conclusions Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC. (Source: Gut)
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Chiu, S. Y.-H., Chuang, S.-L., Chen, S. L.-S., Yen, A. M.-F., Fann, J. C.-Y., Chang, D.-C., Lee, Y.-C., Wu, M.-S., Chou, C.-K., Hsu, W.-F., Chiou, S.-T., Chiu, H.-M. Tags: Endoscopy, Open access, Colon cancer Source Type: research

Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme
Objective Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional ‘full-dose, day-before’ regimen in terms of ADR. Design In a multicentre, randomised, endoscopist-blinded study, 50–69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to rece...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Radaelli, F., Paggi, S., Hassan, C., Senore, C., Fasoli, R., Anderloni, A., Buffoli, F., Savarese, M. F., Spinzi, G., Rex, D. K., Repici, A. Tags: Endoscopy, Colon cancer Source Type: research

Apelin targets gut contraction to control glucose metabolism via the brain
Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. (Source: Gut)
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Fournel, A., Drougard, A., Duparc, T., Marlin, A., Brierley, S. M., Castro, J., Le-Gonidec, S., Masri, B., Colom, A., Lucas, A., Rousset, P., Cenac, N., Vergnolle, N., Valet, P., Cani, P. D., Knauf, C. Tags: Open access Neurogastroenterology Source Type: research

Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing
Conclusion GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development. Trial registration number NCT02344758. (Source: Gut)
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Moreno, M. d. L., Cebolla, A., Munoz-Suano, A., Carrillo-Carrion, C., Comino, I., Pizarro, A., Leon, F., Rodriguez-Herrera, A., Sousa, C. Tags: Open access, Coeliac disease Source Type: research

Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis
Objective To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed. Design Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. ...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Castano-Rodriguez, N., Kaakoush, N. O., Lee, W. S., Mitchell, H. M. Tags: Campylobacter, Salmonella, Shigella, Escherichia coli, Helicobacter pylori, Crohn's disease Inflammatory bowel disease Source Type: research

TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice
Conclusions These results suggest that TGR5 contributes to the glucoregulatory benefits of VSG surgery by promoting metabolically favourable shifts in the circulating bile acid pool. (Source: Gut)
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: McGavigan, A. K., Garibay, D., Henseler, Z. M., Chen, J., Bettaieb, A., Haj, F. G., Ley, R. E., Chouinard, M. L., Cummings, B. P. Tags: Bariatric surgery Source Type: research

Non-alcoholic fatty liver disease as driving force in coronary heart disease?
Non-alcoholic fatty liver disease (NAFLD) has emerged as an imperative public health problem worldwide. NAFLD is now the most common chronic liver disease in high-income countries, and is estimated to affect at least 25%–30% of the general population.1 NAFLD typically exists in a ‘milieu’ of altered metabolism, including abdominal obesity, insulin resistance, dysglycaemia and atherogenic dyslipidaemia.1 Cumulatively, these aetiological factors increase the risk for cardiovascular disease (CVD), and so it is, perhaps, not surprising that CVD is the leading cause of mortality in patients with NAFLD. The cha...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Targher, G. Tags: Commentary Source Type: research

NEMO--CXCL12/CXCR4 axis: a novel vantage point for antifibrotic therapies in chronic pancreatitis?
Chronic pancreatitis (CP) is a common GI disorder with an incidence of 4/100 000 and a prevalence of 41/100 000.1 Owing to the chronic nature of the disease, patients with CP are often admitted to hospital and represent a serious socioeconomic burden across continents. Patients with CP have an increased mortality by more than threefold compared with the normal population, and the 20-year survival rate is reduced to 45% compared with 65% of the normal population.1 The disease mostly occurs in repeated episodes of acute inflammatory bouts of the pancreas parenchyma that progressively leads to exocrine and endocrine...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Neesse, A., Ellenrieder, V. Tags: Commentary Source Type: research

Prognostic RNAs in oesophageal squamous cell carcinoma: small is beautiful
Oesophageal cancer is a deadly malignancy and is highly heterogeneous at the histological, geographical and molecular levels. It is broadly divided into adenocarcinomas and oesophageal squamous cell carcinomas (OSCCs). OSCCs are particularly prevalent in Asia and Africa where the disease has been linked to tobacco smoking, alcohol consumption and population-specific genetic risk variants.1 Clinically, oesophagectomy is the standard of care for curative therapy, usually proceeded by neoadjuvant chemotherapy/concurrent chemoradiotherapy, or in some cases definitive chemoradiotherapy without surgery. Unfortunately, the majori...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Tan, P., Petty, R. Tags: Commentary Source Type: research

Next generation of small molecules in inflammatory bowel disease
Introduction Inflammatory bowel disease (IBD) encompasses two major entities: ulcerative colitis (UC) and Crohn's disease (CD).1 Both are chronic, progressive, disabling conditions that require lifelong medical treatment in most cases. IBD has a major impact on the patient's health-related quality of life,2 and the treatment-related costs place a significant burden on healthcare systems.3 Historically, the medical management of IBD has been based on the use of several small-molecule drugs (SMDs), including corticosteroids, immunomodulators (such as azathioprine, 6-mercaptopurine and methotrexate) and aminosalicylates.4 The...
Source: Gut - January 5, 2017 Category: Gastroenterology Authors: Olivera, P., Danese, S., Peyrin-Biroulet, L. Tags: Crohn's disease, Ulcerative colitis Leading article Source Type: research

Ruling in and ruling out with elastography in compensated advanced chronic liver disease
The recent letter by Jansen et al1 presenting an algorithm to rule out clinically significant portal hypertension (CSPH) by combining shear-wave elastography of liver (L-SWE) and spleen (S-SWE) is an important contribution to the increasing knowledge regarding non-invasive assessment of patients with compensated advanced chronic liver disease (cACLD). Baveno VI recommendations focused on transient elastography as a tool to rule in CSPH in patients with the authors cACLD of viral etiology,2 3 but there is no doubt that other related elastography techniques should work similarly. Also, recent UK guidelines on variceal bleedi...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Augustin, S., Pons, M., Genesca, J. Tags: PostScript Source Type: research

The appropriate dose and cost of iron replacement therapy in patients with IBD
We read with great interest the article by Lee et al,1 who performed an open-label clinical trial to compare the effects of per os (PO) versus intravenous iron replacement therapy (IRT) for iron deficiency in patients with IBD. They concluded that IRT in patients with iron deficiency or anaemia induced significant shifts in bacterial community structure and metabolite landscape in faeces, and PO iron therapy affected the presence of specific molecular bacterial species. These are impressive findings that raise two important issues. First, Lee et al1 enrolled participants with Crohn’s disease (n=31), UC (n=22) and non...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Dong, R., Zheng, S., Chen, G. Tags: PostScript Source Type: research

Diagnostic accuracy of the gamma-glutamyl transpeptidase to platelet ratio (GPR) using transient elastography as a reference
We read with great interest the letter from Stockdale et al1 in which they concluded that the gamma-glutamyl transpeptidase to platelet ratio (GPR) and aspartate transaminase (AST)-to-platelet ratio index (APRI) would not be ideal for the diagnosis of liver fibrosis in patients with HIV–HBV coinfection from West Africa. In a relatively small cohort of HIV–HBV coinfected subjects (n=100) from Ghana, the authors reported poor sensitivity (57%–67%) and specificity (63%–79%) of GRP and APRI in diagnosing advanced fibrosis (≥F3) and cirrhosis (F4). These findings are interesting, but should be interpr...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Lemoine, M., Thursz, M., Mallet, V., Shimakawa, Y. Tags: PostScript Source Type: research

Effects of enteral polymeric diet on gut microbiota in children with Crohn's disease
We read with great interest the article by Wu et al1 showing that the impact of diet on the composition of the gut microbiota was milder than its impact on metabolites produced by the gut microbiota, in healthy humans. Enteral nutrition is an effective treatment to manage active Crohn's disease (CD) in children.2 CD is known to be associated with gut microbial dysbiosis that is characterised by decreased diversity and imbalances in the intestinal microbiome. Recent evidence indicates that exclusive enteral nutrition (EEN) may affect gut microbiota in children with CD,3 but it remains elusive whether the aforementioned chan...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Guinet-Charpentier, C., Lepage, P., Morali, A., Chamaillard, M., Peyrin-Biroulet, L. Tags: PostScript Source Type: research