Bone marrow Th17 TNF{alpha} cells induce osteoclast differentiation and link bone destruction to IBD
Osteoporosis in IBD has long been attributed to impaired bone formation caused by malabsorption and consequent vitamin D and calcium deficiency or to long-term steroid therapy. However, systemic bone loss is not restricted to chronic inflammatory conditions of the intestine such as IBD or coeliac disease, but is also found in non-intestinal chronic inflammatory conditions including rheumatoid arthritis, ankylosing spondylitis and psoriatric arthritis.1 In a groundbreaking paper in 1999, rheumatologists started to shed light on the process of inflammation-induced bone loss.2 In this work by Kong and colleagues, the initial ...
Source: Gut - June 9, 2015 Category: Gastroenterology Authors: Syrbe, U., Siegmund, B. Tags: Commentary Source Type: research

Environment and invironment in IBDs: partners in crime
IBD are chronic inflammatory disorders of the GI tract of unknown aetiology. Crohn's disease (CD) and UC may present with a variable clinical phenotype, and they run a highly variable disease course with a considerable proportion of patients with CD eventually developing penetrating or stricturing complications.1 The key mechanism underlying the pathogenesis of these diseases is assumed to be a dysregulated immune response to commensal flora in a genetically susceptible host.2 Thus, host genetics, the intestinal microbiota (commensal flora and dysbiosis) and external environmental factors are all thought to play an importa...
Source: Gut - June 9, 2015 Category: Gastroenterology Authors: Lakatos, P. L., Burisch, J. Tags: Commentary Source Type: research

Correction
Kalla R, Ventham NT, Kennedy NA, et al. MicroRNAs: new players in inflammatory bowel disease. Gut 2015;64:504–13. The Open Access licence has been corrected to CC BY. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Tags: Correction Source Type: research

The natural course of serrated lesions: a difficult enigma to resolve
To the editor, The serrated pathway is an established sequence to colorectal cancer (CRC), but little is known about the exact malignant potential of serrated polyps (SPs). Therefore, we have read with great interest the article by Holme et al1 who evaluated the long-term risk of CRC in individuals with large (≥10 mm) SPs as well as the natural course of these lesions. Based on their results, the authors state that the increased CRC risk for individuals with large SPs may not be due to the malignant growth of the SP itself, but rather to an overall field effect in patients with these lesions. However, this statemen...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: IJspeert, J. E. G., Bastiaansen, B. A. J., Fockens, P., Dekker, E. Tags: PostScript Source Type: research

Early effect of screening programmes on incidence and mortality rates of colorectal cancer
We thank Logan and Halloran for their interest in our study1 and admit that we were equally surprised at the early impact of screening programmes on colorectal cancer mortality rates.2 With respect to incidence trends, rates peaked during the prevalence round and showed a sharp reduction below the prescreening values within 5 years of screening set-up.2 These results are in line with the few evidences in the literature that evaluated the effect of population screening programmes based on the faecal occult blood test. Ventura et al3 compared the cumulative incidence between cohorts of screened and non-screened individu...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Zorzi, M., Fedeli, U. Tags: PostScript Source Type: research

Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test
Sir, Zorzi et al1 are to be commended for their timely analysis of the impact of using a faecal immunochemical test (FIT) on colorectal cancer mortality in their screening programme. The 24% colorectal cancer mortality reduction they report will surely give impetus to efforts to introduce FIT into other screening programmes. As they rightly observe, the impact of these newer screening tests is likely only to be determined from observational studies such as their study rather than further randomised trials. Nevertheless, some of their findings are quite surprising. It is remarkable that the mortality reduction they report s...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Logan, R. F., Halloran, S. P. Tags: PostScript Source Type: research

Discontinuation of long-term NA therapy in HBeAg-negative chronic hepatitis B
We read the article of Seto et al1 and we were really surprised by a very high rate of virological relapse (91%), much higher than 58% in a similar study by Jeng et al,2 and their conclusion that "the high rates of virologic relapse suggest that nucleos(t)ide analogue (NA) therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance". However, in hitherto conducted studies in Asian and Western patients with HBeAg-negative chronic hepatitis B, virological relapses alone defined as HBV DNA>2000 IU/mL with normal ALT levels, have first been monitored at frequent int...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Hadziyannis, S., Liaw, Y.-F. Tags: PostScript Source Type: research

Virtual portal pressure gradient from anatomic CT angiography
By definition, portal hypertension means pathological elevation of the portal pressure gradient (PPG), the direct measurement of which is extremely invasive. This has prompted the use of the less invasive hepatic venous pressure gradient (HVPG), widely accepted as the PPG equivalent.1–3 In a recent article in Gut, HVPG was used as the only criterion to assess haemodynamic response (reduction in HVPG of ≥20% or to values
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Qi, X., Li, Z., Huang, J., Zhu, Y., Liu, H., Zhou, F., Liu, C., Xiao, C., Dong, J., Zhao, Y., Xu, M., Xing, S., Xu, W., Yang, C. Tags: PostScript Source Type: research

A no biopsy strategy for adult patients with suspected coeliac disease: making the world gluten-free
In this study the PPV of anti-tissue transglutaminase antibody (tTG) was only 28.6%, despite sensitivity and specificity of greater than 90%, which only increased to 71.7% when combined with a positive endomysial antibody (EMA). In simple terms if we follow the approach advocated by Austin and colleagues 3... (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Kurien, M., Ludvigsson, J. F., Sanders, D. S., on behalf of the authors of the BSG guidelines Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the recruitment of CD8+ T cells to the intestine and the role that distinct microenvironments within the infected intestine can play in regulating cell development was investigated. The authors used Yersinia pseudotuberculosis (Yptb) infection as a model to... (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance
Key messages Colorectal cancer can occur via more than one molecular pathway. The serrated pathway probably accounts for 20%–30% of colorectal cancer. Histopathological nomenclature for serrated lesions varies internationally. We suggest the terms hyperplastic polyp (HP), sessile serrated polyp (SSP), and traditional serrated adenoma to describe these lesions. Colonoscopy is the best detection tool for serrated polyps, but detection rates are variable. Chromoendoscopy and slower withdrawal time are the only interventions that have been demonstrated to increase serrated lesion detection. High-definition endoscopy and ...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: East, J. E., Vieth, M., Rex, D. K. Tags: Endoscopy, GUT Recent advances in clinical practice, Colon cancer Source Type: research

Effectiveness, training and quality assurance of colonoscopy screening for colorectal cancer
Screening for colorectal cancer has been proven to be effective in reducing colorectal cancer incidence and mortality. While the precise benefit of screening exclusively by colonoscopy is not yet known, unarguably, the exam is central to the success of any screening programme. The test affords the opportunity to detect and resect neoplasia across the entire large bowel and is the definitive examination when other screening tests are positive. However, colonoscopy is invasive and often requires sedation as well as extensive bowel preparation, all of which puts the patient at risk. Furthermore, the test can technically be de...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Robertson, D. J., Kaminski, M. F., Bretthauer, M. Tags: Endoscopy, GUT Recent advances in clinical practice, Colon cancer Source Type: research

Enhanced expression of BMP6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease
Conclusions Steatosis-induced upregulation of BMP6 in NAFLD is hepatoprotective. Induction of BMP6-signalling may be a promising antifibrogenic strategy. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Arndt, S., Wacker, E., Dorn, C., Koch, A., Saugspier, M., Thasler, W. E., Hartmann, A., Bosserhoff, A. K., Hellerbrand, C. Tags: Nonalcoholic steatosis Hepatology Source Type: research

Serological and clinical outcomes of horizontally transmitted chronic hepatitis B infection in New Zealand Māori: results from a 28-year follow-up study
We report the 28-year follow-up data on clinical and serological outcomes in indigenous New Zealand Māori with early horizontally acquired HBV. Methods In 1984, community seroprevalence study identified 572 HBsAg-positive individuals, followed for 28 years. Liver-related mortality and hepatocellular carcinoma (HCC) incidence were compared between these 572 HBV carriers and 1140 HBsAg-negative matched case-controls. Surviving HBsAg-positive individuals have been followed up in 2012 with clinical assessment, blood tests and liver transient elastography. Rates of hepatitis B e-antigen (HBeAg) and HBsAg seroconversion w...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Lim, T. H., Gane, E., Moyes, C., Borman, B., Cunningham, C. Tags: Hepatic cancer Hepatology Source Type: research

Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication
Conclusions Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Florimond, A., Chouteau, P., Bruscella, P., Le Seyec, J., Merour, E., Ahnou, N., Mallat, A., Lotersztajn, S., Pawlotsky, J.-M. Tags: Cirrhosis Hepatology Source Type: research

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study
Objective To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. Design In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Hezode, C., Hirschfield, G. M., Ghesquiere, W., Sievert, W., Rodriguez-Torres, M., Shafran, S. D., Thuluvath, P. J., Tatum, H. A., Waked, I., Esmat, G., Lawitz, E. J., Rustgi, V. K., Pol, S., Weis, N., Pockros, P. J., Bourliere, M., Serfaty, L., Vierling, Tags: Hepatology Source Type: research

Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice
Conclusions Mnk1 is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and eIF4E phosphorylation. It is required for the physiological secretory response of acinar cells and for the homeostatic response to caerulein administration during acute pancreatitis. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Cendrowski, J., Lobo, V. J. S.-A., Sendler, M., Salas, A., Kuhn, J.-P., Molero, X., Fukunaga, R., Mayerle, J., Lerch, M. M., Real, F. X. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Long-term risk of colorectal cancer in individuals with serrated polyps
Conclusions Individuals with large serrated polyps have an increased risk of CRC, comparable with individuals with advanced adenomas. However, this risk may not be related to malignant growth of the serrated polyp. Trial registration number The Norwegian Colorectal Cancer Screening trial is registered at clinicaltrials.gov (NCT00119912). (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Holme, O., Bretthauer, M., Eide, T. J., Loberg, E. M., Grzyb, K., Loberg, M., Kalager, M., Adami, H.-O., Kjellevold, O., Hoff, G. Tags: Endoscopy, Colon cancer Source Type: research

FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study
Conclusions No differences in mPFS were found between the FCGR polymorphisms HH and the others and VV versus the others in KRAS-WT mCRC patients refractory to irinotecan, oxaliplatin and 5-fluorouracil treated with cetuximab. We cannot confirm the effects of other IgG1 antibodies, which may be weaker than previously suggested. Other markers may be needed to study the actual host antibody response to cetuximab. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Geva, R., Vecchione, L., Kalogeras, K. T., Jensen, B. V., Lenz, H.-J., Yoshino, T., Paez, D., Montagut, C., Souglakos, J., Cappuzzo, F., Cervantes, A., Frattini, M., Fountzilas, G., Johansen, J. S., Hogdall, E. V., Zhang, W., Yang, D., Yamazaki, K., Nishi Tags: Colon cancer Source Type: research

Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays
Conclusions This culture system will facilitate the study of interindividual, functional studies of human intestinal epithelial cells, including host–microbial interactions. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: VanDussen, K. L., Marinshaw, J. M., Shaikh, N., Miyoshi, H., Moon, C., Tarr, P. I., Ciorba, M. A., Stappenbeck, T. S. Tags: Editor's choice Colon Source Type: research

Intestinal steroidogenesis controls PPAR{gamma} expression in the colon and is impaired during ulcerative colitis
Conclusions These results demonstrate cortisol control of PPAR expression in CEC, highlighting cortisol production deficiency in colonocytes as a key molecular event in the pathophysiology of UC. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Bouguen, G., Langlois, A., Djouina, M., Branche, J., Koriche, D., Dewaeles, E., Mongy, A., Auwerx, J., Colombel, J.-F., Desreumaux, P., Dubuquoy, L., Bertin, B. Tags: Ulcerative colitis Inflammatory bowel disease Source Type: research

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study
Objective Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. Design In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Reinisch, W., Panes, J., Khurana, S., Toth, G., Hua, F., Comer, G. M., Hinz, M., Page, K., O'Toole, M., Moorehead, T. M., Zhu, H., Sun, Y., Cataldi, F. Tags: Inflammatory bowel disease Source Type: research

Human buccal epithelium acquires microbial hyporesponsiveness at birth, a role for secretory leukocyte protease inhibitor
Conclusions We identify SLPI as a new player in acquisition of microbial hyporesponsiveness by buccal and intestinal epithelium in the first weeks after microbial colonisation. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Menckeberg, C. L., Hol, J., Simons-Oosterhuis, Y., Raatgeep, H. C., de Ruiter, L. F., Lindenbergh-Kortleve, D. J., Korteland-van Male, A. M., El Aidy, S., van Lierop, P. P. E., Kleerebezem, M., Groeneweg, M., Kraal, G., Elink-Schuurman, B. E., de Jongste, Tags: Crohn's disease Gut microbiota Source Type: research

Recurrent cholangitis in a 65-year-old man
Part 1: Case report A 65-year-old man was referred for assessment of advanced liver disease. Seventeen years previously he had been diagnosed with ulcerative colitis, and 7 years later with primary sclerosing cholangitis (PSC). After several episodes with variceal bleeding caused by secondary biliary cirrhosis, a transjugular intrahepatic portosystemic shunt (TIPS) was created. Because of recurrent bacterial cholangitis, endoscopic retrograde cholangiography was performed, showing irregular narrowing of the intrahepatic bile ducts with saccular dilatations, findings considered compatible with PSC (figure 1). Also, a r...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Joosse, M. E., Schipper, M. E. I., Libbrecht, L., van Buuren, H. R., de Man, R. A. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice
Conclusions CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp. population. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Anhe, F. F., Roy, D., Pilon, G., Dudonne, S., Matamoros, S., Varin, T. V., Garofalo, C., Moine, Q., Desjardins, Y., Levy, E., Marette, A. Tags: Gut microbiota Source Type: research

Surveillance in patients with long-segment Barrett's oesophagus: a cost-effectiveness analysis
Conclusions Based on a Dutch healthcare perspective and assuming a willingness-to-pay threshold of 35.000 per QALY, surveillance with EMR and RFA for HGD or early OAC, and oesophagectomy for advanced OAC is cost-effective every 5 years for ND and every 3 years for LGD. (Source: Gut)
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Kastelein, F., van Olphen, S., Steyerberg, E. W., Sikkema, M., Spaander, M. C. W., Looman, C. W. N., Kuipers, E. J., Siersema, P. D., Bruno, M. J., de Bekker-Grob, E. W., Biermann, Geldof, van der Valk, ter Borg, Giard, Felt, Meijer, Alderliesten, Heinhui Tags: Oesophageal cancer Oesophagus Source Type: research

Piecing together the key players of fibrosis in chronic hepatitis C: what roles do non-hepatic liver resident cell types play?
WHO estimates suggest that worldwide 150–200 million people are chronic carriers of HCV. Of these up to 30% will develop chronic liver inflammation and fibrosis and progress to cirrhosis or hepatocellular carcinoma (HCC) in the long term. New HCV infections are still occurring, and most HCV carriers are unaware of their status. Therefore incidences of HCV-induced liver disease and cancer are predicted to rise in the coming decade in spite of important recent progress in the development of direct antiviral agents. These new treatments appear to have greatly improved efficacies and safety profiles combined with a high ...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Bartosch, B. Tags: Commentary Source Type: research

Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C
With the introduction of direct-acting antivirals (DAA), the treatment for chronic hepatitis C is evolving at an astonishingly rapid pace.1 Among DAAs, HCV NS5A inhibitors show substantial promise as anti-HCV therapeutics. NS5A inhibitors in clinical development include daclatasvir (DCV), ledipasvir, ombitasvir and MK-8742.2 With in vitro anti-HCV activities in the low picomolar range, these represent the most potent class of DAAs to target HCV. The HCV NS5A protein is known to function in multiple aspects of the HCV life cycle, including roles in viral replication and assembly, as well as complex interactions with cellula...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Aghemo, A., De Francesco, R. Tags: Commentary Source Type: research

Intestinal epithelial spheroids: new tools for studying gastrointestinal diseases
The intestinal tract is one of the most complex organs of our body because it has to perform several functions, including digestion and absorption of nutrients. Being exposed to a continuous insult by the local microbiota, the intestinal epithelium is constantly renewed from Lgr5+ stem cell progenitors located in the crypts of Lieberkuhn.1 These progenitors have been recently exploited to regenerate ‘mini-guts’ (organoids) in vitro.2 An appropriate cocktail of small molecules and growth factors has been identified that preserves stemness but also favours the differentiation of enterocytes and Paneth cells thus ...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Rescigno, M. Tags: Commentary Source Type: research

Failure of interleukin 13 blockade in ulcerative colitis
Contrary to a decade ago, clinical development in ulcerative colitis (UC) has become highly active with multiple promising innovative assets currently in early and late phase clinical studies. The anti-integrin α4β7 monoclonal antibody vedolizumab has been leading this wave, and has received marketing authorisation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on an excellent efficacy and safety record. One of the targets that had raised high hopes several years ago was interleukin 13 (IL-13), together with IL-4 and IL-5 the signature cytokine of a T helper 2 (Th2) im...
Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Tilg, H., Kaser, A. Tags: Commentary Source Type: research

Author response: oral contraceptives and Crohn's disease
We appreciate the suggestion by Dr Rhodes to further evaluate the link between oral contraceptive (OC) use and risk of Crohn's disease according to the anatomical location of disease involvement.1 We agree that a plausible mechanism for the link between OC use and risk of Crohn's disease may be through the effect of oestrogen on subacute thrombosis, leading to the development of multifocal ischaemia and infarction of the colon that manifests as colitis. In our study,2 we documented 315 incident cases of Crohn's disease through 2007 in Nurses’ Health Study II (NHS II) and 2008 in NHS I. Among these cases, 141 (45%) we...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Khalili, H., Chan, A. T. Tags: PostScript Source Type: research

Successful delivery of clinical gastroenterology studies in the UK
Recent publications in Gut1 2 have highlighted the beneficial role of the National Institute for Health Research (NIHR) Clinical Research Network in supporting clinical gastroenterology research in the UK.3 On an European level, the European Clinical Research Infrastructures Network provides integrated support to multinational clinical research projects in partner countries. The overarching aim of the NIHR Clinical Research Network is to maximise clinical research delivery by providing the infrastructure that allows high-quality studies to be undertaken in the NHS. The support available encompasses many aspects of the stud...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Hull, M. A., McLaughlin, J. T. Tags: PostScript Source Type: research

Authors' response: virus-host interactions in HBV-related hepatocellular carcinoma: more to be revealed?
We acknowledge Cao et al1 for being interested in our recent study on molecular features of hepatitis B related hepatocellular carcinoma (HBV-related HCC).2 As they suggested, we searched for the HBx-LINE1 chimerical transcript recently identified in a Chinese population of HBV-related HCC by Lau et al3 in our series of HCC treated in France.2 To this aim, we have selected and analysed 50 HBV-related HCC tumours which were included in our last report.2 Total RNAs were extracted using Trizol (Invitrogen) from frozen tissues and converted into cDNA by SuperScript VILO cDNA Synthesis Kit (Life Technologies). Reverse-transcrib...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Cao, Q., Imbeaud, S., Datta, S., Zucman-Rossi, J. Tags: PostScript Source Type: research

Virus-host interactions in HBV-related hepatocellular carcinoma: more to be revealed?
Sir, We read with interest the paper by Amaddeo et al1 describing a comprehensive and integrative study to understand the molecular characteristics of HBV-related hepatocellular carcinoma (HCC). Chronic HBV infection is one of the most common causes of HCC. Although integration of viral gene into host genome has been implicated as an important oncogenic mechanism, a series of studies have reported that both direct and indirect hepatocarcinogenic actions of HBV infection exist. Amaddeo et al1 found a frequent inactivation of p53 and overexpression of stem cell-related genes in HBV-infected HCC tumours. Most importantly, TP5...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Cao, W., Peppelenbosch, M. P., Pan, Q. Tags: PostScript Source Type: research

Authors' response: Bile acids are important in the pathophysiology of IBS
We thank Dr Aziz et al1 for expressing their interest in our recent paper, where we demonstrate that bile acids entering the colon may be an important factor for generation of part of the symptoms in patients who fulfil current diagnostic criteria for IBS.2 We agree with their comment that clinicians managing patients with IBS should be aware of the fact that an abnormal 75Se-labelled homocholic acid-taurine (75SeHCAT) test is quite a common finding in patients with non-constipated IBS, and that treating patients with IBS and an abnormal 75SeHCAT test with a bile acid binding agent may improve some of the key symptoms in t...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Bajor, A., Tornblom, H., Rudling, M., Ung, K.-A., Simren, M. Tags: PostScript Source Type: research

Screening for bile acid diarrhoea in suspected irritable bowel syndrome
We read the paper by Bajor et al with interest.1 The authors demonstrated that 18% of patients who meet criteria for IBS may have underlying bile acid diarrhoea (BAD), using 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning. This issue has been the subject of a previous systematic review and meta-analysis2 which reported that up to 30% of individuals with IBS had evidence of idiopathic BAD. However, many of the included studies were retrospective, and few used accepted symptom-based criteria to define the presence of IBS, underlining the importance of the data from Bajor et al1 who recruited a well characterised and ri...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Aziz, I., Kurien, M., Sanders, D. S., Ford, A. C. Tags: PostScript Source Type: research

GI highlights from the literature
This study characterised the normal human and IBD enteric virome and... (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches
The recent approval of two immune checkpoint inhibitors for the treatment of malignant melanoma has sparked great interest by physicians and basic scientists searching for novel therapeutics for GI cancer. Chronic inflammation is recognised as a major risk factor for the development of hepatocellular carcinoma (HCC) and makes this type of cancer a potentially ideal target for an immune based treatment approach. Further evidence for a critical role of immune responses in patients with HCC is derived from the fact that immune signatures and profiles predict patients’ outcome as well as the fact that tumour-induced spon...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Greten, T. F., Wang, X. W., Korangy, F. Tags: GUT Recent advances in clinical practice, Hepatic cancer Source Type: research

Pathobiology of liver fibrosis: a translational success story
Reversibility of hepatic fibrosis and cirrhosis following antiviral therapy for hepatitis B or C has advanced the prospect of developing antifibrotic therapies for patients with chronic liver diseases, especially non-alcoholic steatohepatitis. Mechanisms of fibrosis have focused on hepatic stellate cells, which become fibrogenic myofibroblasts during injury through ‘activation’, and are at the nexus of efforts to define novel drug targets. Recent studies have clarified pathways of stellate cell gene regulation and epigenetics, emerging pathways of fibrosis regression through the recruitment and amplification of...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Lee, Y. A., Wallace, M. C., Friedman, S. L. Tags: GUT Recent advances in basic science, Cirrhosis Source Type: research

Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas
Conclusions Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Amaddeo, G., Cao, Q., Ladeiro, Y., Imbeaud, S., Nault, J.-C., Jaoui, D., Gaston Mathe, Y., Laurent, C., Laurent, A., Bioulac-Sage, P., Calderaro, J., Zucman-Rossi, J. Tags: Open access, Hepatic cancer Hepatology Source Type: research

Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection
This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. Design We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. Results Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Fitzmaurice, K., Hurst, J., Dring, M., Rauch, A., McLaren, P. J., Gunthard, H. F., Gardiner, C., Klenerman, P., Irish HCV Research Consortium and the Swiss HIV Cohort Study, Courtney, G., Crosbie, O., Crowe, J., Fanning, L., Hegarty, J., Kelleher, D., Law Tags: Open access Hepatology Source Type: research

Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis
Objectives We used a screening strategy of global serum microRNA (miRNA) profiling, followed by a second stage of independent replication and exploration of liver expression of selected miRNAs to study: (1) the circulating miRNA signature associated with non-alcoholic fatty liver disease (NAFLD) progression and predictive power, (2) the role of miRNAs in disease biology and (3) the association between circulating miRNAs and features of the metabolic syndrome. Methods The study used a case-control design and included patients with NAFLD proven through biopsy and healthy controls. Results Among 84 circulating miRNAs analys...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Pirola, C. J., Fernandez Gianotti, T., Castano, G. O., Mallardi, P., San Martino, J., Mora Gonzalez Lopez Ledesma, M., Flichman, D., Mirshahi, F., Sanyal, A. J., Sookoian, S. Tags: Nonalcoholic steatosis Hepatology Source Type: research

Vitamin D counteracts fibrogenic TGF-{beta} signalling in human hepatic stellate cells both receptor-dependently and independently
Conclusions VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Beilfuss, A., Sowa, J.-P., Sydor, S., Beste, M., Bechmann, L. P., Schlattjan, M., Syn, W.-K., Wedemeyer, I., Mathe, Z., Jochum, C., Gerken, G., Gieseler, R. K., Canbay, A. Tags: Cirrhosis, Nonalcoholic steatosis Hepatology Source Type: research

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test
Conclusions FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Zorzi, M., Fedeli, U., Schievano, E., Bovo, E., Guzzinati, S., Baracco, S., Fedato, C., Saugo, M., Dei Tos, A. P. Tags: Colon cancer Source Type: research

Prediction of proximal advanced neoplasia: a comparison of four existing sigmoidoscopy-based strategies in a Chinese population
Conclusions The US criteria had the highest sensitivity for detection of APN and lowest NNS and the UK score had the highest specificity and the lowest NNR. The performance of all these four criteria to predict APN is limited, highlighting an urgent need to devise a novel APN prediction system for Asian subjects. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Wong, M. C. S., Ching, J. Y. L., Ng, S. C., Wong, S., Chan, V. C. W., Shum, J. P., Lam, T. Y. T., Luk, A. K. C., Sung, J. J. Y. Tags: Endoscopy, Colon cancer Source Type: research

Targeting tumour necrosis factor receptor 1 assembly reverses Th17-mediated colitis through boosting a Th2 response
Conclusions The Th2 cytokine milieu induced by PLAD.Fc rebalanced T-helper cell subsets and conferred a protection against colitis in BLIMP-1 knockout mice. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Fu, S.-H., Lin, M.-H., Yeh, L.-T., Wang, Y.-L., Chien, M.-W., Lin, S.-H., Chang, D.-M., Sytwu, H.-K. Tags: Crohn's disease, Diarrhoea Inflammatory bowel disease Source Type: research

Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch
Conclusions Significant gene expression alterations exist in an apparently unaffected proximal SB. Alterations in the pouch and the proximal SB were comparable, suggesting that inflammation may not be limited to the pouch, but that it extends to the proximal SB. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Yanai, H., Ben-Shachar, S., Baram, L., Elad, H., Gitstein, G., Brazowski, E., Tulchinsky, H., Pasmanik-Chor, M., Dotan, I. Tags: Ulcerative colitis Inflammatory bowel disease Source Type: research

IL-9 and its receptor are predominantly involved in the pathogenesis of UC
Conclusions Our results provide evidence that IL-9 is predominantly involved in the pathogenesis of UC suggesting that targeting IL-9 might become a therapeutic option for patients with UC. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Nalleweg, N., Chiriac, M. T., Podstawa, E., Lehmann, C., Rau, T. T., Atreya, R., Krauss, E., Hundorfean, G., Fichtner-Feigl, S., Hartmann, A., Becker, C., Mudter, J. Tags: Inflammatory bowel disease Source Type: research

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants
Conclusions In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. Trial registration number NCT01111864. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Jaeggi, T., Kortman, G. A. M., Moretti, D., Chassard, C., Holding, P., Dostal, A., Boekhorst, J., Timmerman, H. M., Swinkels, D. W., Tjalsma, H., Njenga, J., Mwangi, A., Kvalsvig, J., Lacroix, C., Zimmermann, M. B. Tags: Clostridium difficile, Diarrhoea Gut microbiota Source Type: research

Unusual cause of a giant antral ulcer
Clinical presentation A 31-year-old man visited our gastroenterology clinic owing to continuous epigastric pain lasting 3 months, diarrhoea during the previous month and an associated 10 kg weight loss. An ulcer in his antrum was discovered by oesophagogastroduodenoscopy (EGD), and he took a proton-pump inhibitor for a month. However, his clinical symptoms and ulcer worsened. He denied melena, haematemesis, fever, arthralgia, recurrent aphthous ulcer and genital ulcer. He had a>10-year history of asthma and eczema. Physical examination was unremarkable except for emaciation and upper abdominal tenderness. Laborator...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Wang, X.-Y., Dai, Y.-H., Yang, Y.-M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research