Beta-blockers in patients with cirrhosis and ascites: type of beta-blocker matters
Letter to the Editor: We read with great interest the article by Leithead et al,1 which showed that non-selective beta-blocker (NSBB) therapy was found to be beneficial for patients with ascites, and associated with reduced waitlist deaths even in those with refractory ascites. The study by Sersté et al2 was the first to suggest that NSBB therapy is associated with an increased mortality in patients with cirrhosis and refractory ascites. This led to the NSBB ‘therapeutic window’ hypothesis that claimed that the window would close once a patient developed refractory ascites.3 However, the issue remains co...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Njei, B., McCarty, T. R., Garcia-Tsao, G. Tags: PostScript Source Type: research

Is human albumin solution really the best resuscitation fluid for patients with advanced cirrhosis?
Dear Sirs, We read with interest the revised consensus recommendations for management of acute kidney injury (AKI) ) in cirrhosis by the International Club of Ascites.1 We are concerned that plasma volume expansion only with albumin is recommended for stage 2 and 3 AKI and do not believe that this represents a balanced view of the available evidence. No one doubts that fluid resuscitation is an integral part of the management of AKI; however, studies to date have not established class 1 evidence for an advantage of the use of albumin over other colloids or crystalloids. It can be argued that albumin may represent a superio...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: O'Brien, A., China, L., on behalf of the ATTIRE Trial Management Committee, on behalf of the ATTIRE Trial Management Committee, Forrest, Ryder, Wright, Portal, O'Beirne, Shabir, Skene, Chandler, Garcia-Hernandez Tags: PostScript Source Type: research

Propranolol improves endothelial dysfunction in advanced cirrhosis: the 'endothelial exhaustion hypothesis
We read with interest the recent work of Leithead and coworkers about the use of non-selective β-blockers (NSBBs) in patients in the transplant waiting list. They studied 322 patients, among those 117 had refractory ascites and observed higher survival rate in those using NSBB, including the ones with refractory ascites (HR mortality=0.35; confidence interval (CI) 95%: 0.14 to 0.86).1 However, the use of NSBB has been a polemic issue since the hypothesis proposed by Krag and coworkers suggesting the existence of a ‘therapeutic window’, according to which NSBB would not be beneficial to patients in early or...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Brito-Azevedo, A., Perez, R. d. M., Coelho, H. S. M., Fernandes, E. d. S. M., Castiglione, R. C., Villela-Nogueira, C. A., Bouskela, E. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceViruses in our gut—friend or foe? Yang JY, Kim MS, Kim E, et al. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production. Immunity 2016;44:889–900. Gut homeostasis is regulated by complex interactions between genetic and environmental factors and the host's immune system. When this homeostasis is disrupted, gut inflammation ensues. Microbial imbalance, also known as dysbiosis, plays a critical role in intestinal pathology; however, previous studies have only focused on commensal bacteria despite metagenomic studies revealin...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Erratum: MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor
Kong KL, Kwong DLW, Chan TH-M, et al. MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut 2012;61:33–42. In the previous correction (the representative image of lung (KYSE30-375+) in a SCID mouse in Figure 4 panel D) we have been informed by the authors that this figure was supplied in error. The updated figure is published here.   (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Tags: Correction Source Type: research

PHLDA3 overexpression in hepatocytes by endoplasmic reticulum stress via IRE1-Xbp1s pathway expedites liver injury
Conclusions ER stress in hepatocytes induces PHLDA3 via IRE1–Xbp1s pathway, which facilitates liver injury by inhibiting Akt. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Han, C. Y., Lim, S. W., Koo, J. H., Kim, W., Kim, S. G. Tags: Cirrhosis, Open access Hepatology Source Type: research

The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa
Conclusions The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Lemoine, M., Shimakawa, Y., Nayagam, S., Khalil, M., Suso, P., Lloyd, J., Goldin, R., Njai, H.-F., Ndow, G., Taal, M., Cooke, G., D'Alessandro, U., Vray, M., Mbaye, P. S., Njie, R., Mallet, V., Thursz, M. Tags: Cirrhosis, Open access Hepatology Source Type: research

Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study
Conclusions Diabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Kwok, R., Choi, K. C., Wong, G. L.-H., Zhang, Y., Chan, H. L.-Y., Luk, A. O.-Y., Shu, S. S.-T., Chan, A. W.-H., Yeung, M.-W., Chan, J. C.-N., Kong, A. P.-S., Wong, V. W.-S. Tags: Nonalcoholic steatosis Hepatology Source Type: research

The applicability of hepatocellular carcinoma risk prediction scores in a North American patient population with chronic hepatitis B infection
Conclusions Although all models predicted the risk of HCC, models that incorporated parameters of liver function or cirrhosis (CU-HCC/GAG-HCC) were most accurate. Low-risk patients likely require reduced HCC surveillance. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Abu-Amara, M., Cerocchi, O., Malhi, G., Sharma, S., Yim, C., Shah, H., Wong, D. K., Janssen, H. L. A., Feld, J. J. Tags: Hepatitis B, Hepatic cancer Hepatology Source Type: research

Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP
Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Mukherjee, R., Mareninova, O. A., Odinokova, I. V., Huang, W., Murphy, J., Chvanov, M., Javed, M. A., Wen, L., Booth, D. M., Cane, M. C., Awais, M., Gavillet, B., Pruss, R. M., Schaller, S., Molkentin, J. D., Tepikin, A. V., Petersen, O. H., Pandol, S. J. Tags: Pancreas and biliary tract, Pancreatitis, Open access Source Type: research

Pathogenicity of IgG in patients with IgG4-related disease
Conclusions IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Shiokawa, M., Kodama, Y., Kuriyama, K., Yoshimura, K., Tomono, T., Morita, T., Kakiuchi, N., Matsumori, T., Mima, A., Nishikawa, Y., Ueda, T., Tsuda, M., Yamauchi, Y., Minami, R., Sakuma, Y., Ota, Y., Maruno, T., Kurita, A., Sawai, Y., Tsuji, Y., Uza, N., Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Refinement of screening for familial pancreatic cancer
Objective Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. Methods IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. Results 253 IAR with a median age of 48 (25–81)&...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Bartsch, D. K., Slater, E. P., Carrato, A., Ibrahim, I. S., Guillen-Ponce, C., Vasen, H. F. A., Matthäi, E., Earl, J., Jendryschek, F. S., Figiel, J., Steinkamp, M., Ramaswamy, A., Vazquez-Sequeiros, E., Munoz-Beltran, M., Montans, J., Mocci, E., Tags: Pancreas and biliary tract, Pancreatic cancer Source Type: research

Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C
Conclusions Dominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Müller, T., Rasool, I., Heinz-Erian, P., Mildenberger, E., Hülstrunk, C., Müller, A., Michaud, L., Koot, B. G. P., Ballauff, A., Vodopiutz, J., Rosipal, S., Petersen, B.-S., Franke, A., Fuchs, I., Witt, H., Zoller, H., Janecke, A. Tags: Diarrhoea, Open access Colon Source Type: research

Activating ERBB2/HER2 mutations indicate susceptibility to pan-HER inhibitors in Lynch and Lynch-like colorectal cancer
Conclusions We developed a high-throughput deep sequencing approach for concomitant MSI and mutational analyses in FFPE specimens. We provided novel insights into clinically relevant alterations in MSI CRC and a rationale for targeting ERBB2/HER2 mutations in Lynch and Lynch-like CRC. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Kloth, M., Ruesseler, V., Engel, C., Koenig, K., Peifer, M., Mariotti, E., Kuenstlinger, H., Florin, A., Rommerscheidt-Fuss, U., Koitzsch, U., Wodtke, C., Ueckeroth, F., Holzapfel, S., Aretz, S., Propping, P., Loeffler, M., Merkelbach-Bruse, S., Odenthal, Tags: Colon cancer Source Type: research

Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk
Objective Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16–20 years). Design At the time of the conscription assessment (1969–1976), height and weight were measured and ESR was assayed. By linkage to the national cancer registry, these conscripts...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Kantor, E. D., Udumyan, R., Signorello, L. B., Giovannucci, E. L., Montgomery, S., Fall, K. Tags: Press releases, Colon cancer Source Type: research

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis
Objective Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. Design 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires as...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Wouters, M. M., Van Wanrooy, S., Nguyen, A., Dooley, J., Aguilera-Lizarraga, J., Van Brabant, W., Garcia-Perez, J. E., Van Oudenhove, L., Van Ranst, M., Verhaegen, J., Liston, A., Boeckxstaens, G. Tags: Gastroenteritis Neurogastroenterology Source Type: research

The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease
Conclusions Thus, we demonstrate previously unappreciated diversity and plasticity of the innate IEL compartment and its loss of differentiation potential in patients with RCDII. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Schmitz, F., Kooy-Winkelaar, Y., Wiekmeijer, A.-S., Brugman, M. H., Mearin, M. L., Mulder, C., Chuva de Sousa Lopes, S., Mummery, C. L., Staal, F. J., van Bergen, J., Koning, F. Tags: Coeliac disease Source Type: research

Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety
Conclusions To limit anti-TNF exposure in utero, anti-TNF can be stopped safely in the second trimester in women with IBD in sustained remission. In patients not in sustained remission, anti-TNF may be continued without clear additional risks to the fetus. We observed excellent 1-year child outcomes compared with children from non-IBD controls. (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: de Lima, A., Zelinkova, Z., van der Ent, C., Steegers, E. A. P., van der Woude, C. J. Tags: Inflammatory bowel disease Source Type: research

Xanthoma striatum palmare
A 31-year-old woman presented with a 7-month history of dark-colour urine, pruritus and xanthoma striatum palmare. Physical examination revealed diffuse yellowish and irregular plaques deposited over her fingers and palmar creases (figure 1). Skin biopsy was performed, which revealed accumulation of foam cells in the dermis (figure 2, arrow). The patient's medical history and family history were unremarkable for other skin diseases or coronary heart disease but 3 years ago, the patient was diagnosed with drug-induced liver injury (DILI) after an episode of jaundice attributed to use of over-the-counter herbal medicine...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Tian, Q.-j., Zhao, X.-y. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett's oesophagus
We examined the association between surveillance indication for EAC diagnosis with or without surveillance programme and EAC stage and treatment receipt in logistic regression models, and with time to death or cancer-related death using a Cox proportional hazards regression model. Results Among 29 536 patients with BE, 424 patients developed EAC during a mean follow-up of 5.0 years. A total of 209 (49.3%) patients with EAC were in BE surveillance programme and were diagnosed as a result of surveillance endoscopy. These patients were more likely to be diagnosed at an early stage (stage 0 or 1: 74.7% vs 56.2, p
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: El-Serag, H. B., Naik, A. D., Duan, Z., Shakhatreh, M., Helm, A., Pathak, A., Hinojosa-Lindsey, M., Hou, J., Nguyen, T., Chen, J., Kramer, J. R. Tags: Editor's choice, Oesophageal cancer Oesophagus Source Type: research

Transition from childhood to adulthood in coeliac disease: the Prague consensus report
The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between ...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Ludvigsson, J. F., Agreus, L., Ciacci, C., Crowe, S. E., Geller, M. G., Green, P. H. R., Hill, I., Hungin, A. P., Koletzko, S., Koltai, T., Lundin, K. E. A., Mearin, M. L., Murray, J. A., Reilly, N., Walker, M. M., Sanders, D. S., Shamir, R., Troncone, R. Tags: Open access, Coeliac disease Guidelines Source Type: research

Why is one arm stronger than two arms? IgG4 antibodies in IgG4-related autoimmune pancreatitis
In this issue, Shiokawa et al1 recapitulated the approach, previously established in pemphigus vulgaris,2 of passive transfer of IgG1 and IgG4 purified from patients with autoimmune pancreatitis (AIP) type 1 into neonatal Balb/c mice. These patients suffered from IgG4-related disease (IgG4-RD). IgG4-RD is a novel clinical entity that includes a growing number of medical conditions that have the following features in common: diffuse organ swelling or focal mass formation, sclerosing storiforme (whirl-like) fibrosis with a lymphoplasmacytic infiltrate rich in IgG4-bearing plasma cells and elevated levels of serum IgG4. The d...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Mayerle, J., Lerch, M. M., Greinacher, A. Tags: Commentary Source Type: research

Drug development in IBD: from novel target identification to early clinical trials
Introduction The two major forms of IBD, Crohn's disease (CD) and UC, are chronic inflammatory disorders, the pathogenesis of which involves a complex interplay of multiple factors.1 2 The introduction of biological agents has substantially expanded and improved the therapeutic options for IBD, but a large proportion of patients still do not respond or achieve remission in the short term or long term. Thus, there is still a considerable need to improve the treatment of IBD, and significant research efforts are underway to address this unmet need. During the last two decades, the period of time over which the biologics as w...
Source: Gut - July 7, 2016 Category: Gastroenterology Authors: Danese, S., Fiocchi, C., Panes, J. Tags: Crohn's disease Leading article Source Type: research

Gut microbiota produce alcohol and contribute to NAFLD
The hypothesis that alcohol metabolism contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) dates back to 2000 when Cope et al1 reported elevated alcohol concentration in the breath of ob/ob mice and demonstrated that breath alcohol concentration can be reduced by gut microbial intervention with neomycin. In the last 15 years, accumulating evidence in support of this hypothesis has been reported by several groups (reviewed at ref. 2), including the group led by Bergheim, who first reported elevated serum alcohol in NAFLD.3 Previous studies indicated that the elevated alcohol level in NAFLD is a...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Zhu, L., Baker, R. D., Zhu, R., Baker, S. S. Tags: PostScript Source Type: research

Spleen size for the prediction of clinical outcome in patients with primary sclerosing cholangitis
Dear Sir, We read with interest the work of van der Meer et al1 who propose a risk score for patients with chronic Hepatitis C. The authors demonstrate that the assessment of readily available and objective parameters can stratify patients according to the risk of disease progression. Patients with primary sclerosing cholangitis (PSC) usually develop progressive liver fibrosis and end-stage liver disease within 10–20 years.2 Simple and non-invasive means for disease stratification and prediction of prognosis are urgently needed. Indeed, the International PSC Study Group recently declared the research on surrogat...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Ehlken, H., Wroblewski, R., Corpechot, C., Arrive, L., Lezius, S., Hartl, J., Denzer, U. W., Lohse, A. W., Chazouilleres, O., Schramm, C. Tags: PostScript Source Type: research

Red signs and not severity of cirrhosis should determine non-selective {beta}-blocker treatment in Child-Pugh C cirrhosis with small varices: increased risk of hepatorenal syndrome and death beyond 6 months of propranolol use
We read with great interest the updated guidelines recently published by Tripathi et al1 on behalf of the Clinical Services and Standards Committee of the British Society of Gastroenterology on the management of variceal haemorrhage (VH) in patients with cirrhosis. One of the topics of discussion was the primary prevention of VH. To our knowledge, these are the first guidelines in the literature to recommend that the initiation of non-selective β-blockers (NSBBs) in patients with small varices should be determined only by coexisting red signs and not the severity of liver disease as recommended by the recent Baveno's ...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Kalambokis, G. N., Baltayiannis, G., Christou, L., Christodoulou, D. Tags: PostScript Source Type: research

Functional annotation of colorectal cancer susceptibility loci identifies MLH1 rs1800734 associated with MSI patients
Recently, we read the article by Ma et al with great interest. They conducted a comprehensive meta-analysis that nominated 62 variants in 50 candidate genes with high level of cumulative evidence for genetic susceptibility to colorectal cancer (CRC).1 Interestingly, the authors found that 10 variants in 7 genes were graded strong and moderate association with CRC risk. However, functional annotations of these variants remain largely unknown. To investigate their functional relevance, we annotated the variants and their high related single nucleotide polymorphisms (SNPs) (linkage disequilibrium, r2>0.9) using publicly av...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Ma, G., Ge, Y., Gu, D., Du, M., Chu, H., Chen, J., Zhang, Z., Wang, M. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceIntratumour heterogeneity and genomic instability as a marker of patient prognosis  Andor N, Graham TA, Jansen M, et al. Pan-cancer analysis of the extent and consequences of tumour heterogeneity. Nat Med 2016;22:105–13. Intratumour heterogeneity is one of the current cancer research hot topics. The observation that tumours are composed of a large number of diverse clones has provided a potential explanation as to why cancers are hard to treat—the likelihood that a therapeutic resistant clone can evolve is high. However, there is no consensus on the consequence of tumour heterogeneity on the p...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Erratum: The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells
Cioffi M, Trabulo SM, Sanchez-Ripoll Y, et al. The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells. Gut 2015;64:1936-48. Two errors have been corrected in the text. In the paragraph "Knockdown of p21 inhibits CSC phenotypes including chemoresistance", line 5 has been corrected to "... we therefore focused on p21 as it was specifically upregulated in chemoresistant CSCs (figure 2A)". In the same paragraph, line 16 has been corrected to "and became chemosensitive to gemcitabine (figur...
Source: Gut - June 2, 2016 Category: Gastroenterology Tags: Correction Source Type: research

Protease inhibition as new therapeutic strategy for GI diseases
The GI tract is the most exposed organ to proteases, both in physiological and pathophysiological conditions. For digestive purposes, the lumen of the upper GI tract contains large amounts of pancreatic proteases, but studies have also demonstrated increased proteolytic activity into mucosal tissues (both in the upper and lower GI tract), associated with pathological conditions. This review aims at outlining the evidences for dysregulated proteolytic homeostasis in GI diseases and the pathogenic mechanisms of increased proteolytic activity. The therapeutic potential of protease inhibition in GI diseases is discussed, with ...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Vergnolle, N. Tags: GUT Recent advances in basic science, Pancreas and biliary tract, Open access, Colon cancer Source Type: research

Liver PPAR{alpha} is crucial for whole-body fatty acid homeostasis and is protective against NAFLD
Conclusions Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Montagner, A., Polizzi, A., Fouche, E., Ducheix, S., Lippi, Y., Lasserre, F., Barquissau, V., Regnier, M., Lukowicz, C., Benhamed, F., Iroz, A., Bertrand-Michel, J., Al Saati, T., Cano, P., Mselli-Lakhal, L., Mithieux, G., Rajas, F., Lagarrigue, S., Pinea Tags: Nonalcoholic steatosis, Open access Hepatology Source Type: research

Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis
Conclusions These findings demonstrate a new protumourigenic axis involving type I IFN–microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Yang, Y., Lin, X., Lu, X., Luo, G., Zeng, T., Tang, J., Jiang, F., Li, L., Cui, X., Huang, W., Hou, G., Chen, X., Ouyang, Q., Tang, S., Sun, H., Chen, L., Gonzalez, F. J., Wu, M., Cong, W., Chen, L., Wang, H. Tags: Editor's choice, Hepatic cancer Hepatology Source Type: research

CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism
Conclusions Our data show that deletion of CD248 reduces susceptibility to liver fibrosis via an effect on PDGF signalling, making it an attractive clinical target for the treatment of liver injury. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Wilhelm, A., Aldridge, V., Haldar, D., Naylor, A. J., Weston, C. J., Hedegaard, D., Garg, A., Fear, J., Reynolds, G. M., Croft, A. P., Henderson, N. C., Buckley, C. D., Newsome, P. N. Tags: Cirrhosis, Open access Hepatology Source Type: research

Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue
Conclusions PC-secreted exosomes induce lipolysis in subcutaneous adipose tissue; exosomal AM is a candidate mediator of this effect. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Sagar, G., Sah, R. P., Javeed, N., Dutta, S. K., Smyrk, T. C., Lau, J. S., Giorgadze, N., Tchkonia, T., Kirkland, J. L., Chari, S. T., Mukhopadhyay, D. Tags: Pancreas and biliary tract, Pancreatic cancer Source Type: research

BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling
Conclusions Our study helps to unravel the mechanism by which BCL-3 is linked to poor prognosis in colorectal cancer; we suggest that targeting BCL-3 activity represents an exciting therapeutic opportunity potentially increasing the sensitivity of tumour cells to conventional therapy. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Urban, B. C., Collard, T. J., Eagle, C. J., Southern, S. L., Greenhough, A., Hamdollah-Zadeh, M., Ghosh, A., Poulsom, R., Paraskeva, C., Silver, A., Williams, A. C. Tags: Open access, Colon cancer Source Type: research

Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer
Conclusions Batf-dependent IL-23R+IL-6+CD4+ Th17 cells critically control IL-23 driven colitis-associated tumour formation and the progression of sporadic colon tumours. Batf-dependent IL-23R+ T cells represent a potential future therapeutic target limiting CRC progression. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Punkenburg, E., Vogler, T., Büttner, M., Amann, K., Waldner, M., Atreya, R., Abendroth, B., Mudter, J., Merkel, S., Gallmeier, E., Rose-John, S., Neurath, M. F., Hildner, K. Tags: Crohn's disease, Colon cancer Source Type: research

Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima
Objective The cross-immunogenicity of the recently approved infliximab-biosimilar Remsima (CT-P13) with the originator drug Remicade is still unknown. Design Sera of patients with IBD with or without measurable anti-Remicade antibodies to infliximab (ATI) were tested for their cross-reactivity to two batches of Remsima. Experiments were repeated after deglycosylation of Remicade/Remsima, IgG purification, excipients’ dialysis and monomer purification by size exclusion chromatography. Anti-Remicade antibodies were tested for their functional inhibition of TNF-α binding by Remsima/Remicade by competition assay. ...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Ben-Horin, S., Yavzori, M., Benhar, I., Fudim, E., Picard, O., Ungar, B., Lee, S., Kim, S., Eliakim, R., Chowers, Y. Tags: Inflammatory bowel disease Source Type: research

Antibodies to adalimumab are associated with future inflammation in Crohn's patients receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial
Introduction Data on immunogenicity to adalimumab (ADL) therapy in patients with IBD is limited. We performed additional analyses on the Karmiris cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and sustained response. Methods 536 prospectively collected serum samples were available for analysis of ADL concentration and ATA using HMSA. We studied the role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA formation with a Cox proportional hazards model. Mixed model repeated measur...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Baert, F., Kondragunta, V., Lockton, S., Vande Casteele, N., Hauenstein, S., Singh, S., Karmiris, K., Ferrante, M., Gils, A., Vermeire, S. Tags: Inflammatory bowel disease Source Type: research

Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease
Conclusions Central reading of CDEIS and SES-CD had ‘substantial’ to ‘almost perfect’ intra-rater and inter-rater reliability; however, the responsiveness of these instruments is yet to be determined. Trial registration number Clinicaltrials.gov NCT01466374. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Khanna, R., Zou, G., D'Haens, G., Rutgeerts, P., McDonald, J. W. D., Daperno, M., Feagan, B. G., Sandborn, W. J., Dubcenco, E., Stitt, L., Vandervoort, M. K., Donner, A., Luo, A., Levesque, B. G. Tags: Endoscopy, Crohn's disease, Colon cancer Source Type: research

Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger
Conclusions Motilin may be an important regulator involved in the pathogenesis of obesity. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Deloose, E., Janssen, P., Lannoo, M., Van der Schueren, B., Depoortere, I., Tack, J. Tags: Gastrointestinal hormones Neurogastroenterology Source Type: research

Antibiotics promote inflammation through the translocation of native commensal colonic bacteria
Conclusions These findings reveal an unexpected outcome of antibiotic therapy and suggest that bacterial translocation as a result of alterations in the intestinal microflora may provide a link between increasing antibiotic use and the increased incidence of inflammatory disorders. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Knoop, K. A., McDonald, K. G., Kulkarni, D. H., Newberry, R. D. Tags: Gut microbiota Source Type: research

An unusual cause of GI bleeding
Clinical presentation A 62-year-old woman with a history of hypertension and diabetes mellitus presented with 3 days intermittent passage of melena. Physical examination was unremarkable. The pertinent laboratory findings were haemoglobin, 10.3 g/dL (normal range, 12.0–16.0 g/dL); platelet count, 136x103/μL (normal range, 150–400x103/μL); prothrombin time, 11.9 s (control, 10.6 s; international normalised ratio, 0.91); and activated partial thrombin time, 28.1 s (control, 31.3 s). Esophagogastroduodenoscopy (EGD) revealed a 3 cm tumour with a central ulceration and adher...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Chen, T.-H., Chen, Y.-J., Tai, C.-M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

The MUC1 mucin protects against Helicobacter pylori pathogenesis in mice by regulation of the NLRP3 inflammasome
Conclusions MUC1 is an important, previously unidentified negative regulator of the NLRP3 inflammasome. H. pylori activation of the NLRP3 inflammasome is normally tightly regulated by MUC1, and loss of this critical regulation results in the development of severe pathology. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Ng, G. Z., Menheniott, T. R., Every, A. L., Stent, A., Judd, L. M., Chionh, Y. T., Dhar, P., Komen, J. C., Giraud, A. S., Wang, T. C., McGuckin, M. A., Sutton, P. Tags: Stomach and duodenum Helicobacter pylori Source Type: research

Identification and genetic manipulation of human and mouse oesophageal stem cells
Conclusions We developed clonogenic and organotypic culture systems for the quantitative analyses of human and mouse oesophageal stem/progenitor cells and identified novel cell surface marker combinations that enrich for these cells. Using this system, we demonstrate that elimination of p63 inhibits self-renewal of human oesophageal stem/progenitor cells. We anticipate that these esophagosphere culture systems will facilitate studies of oesophageal stem cell biology and may prove useful for ex vivo expansion of human oesophageal stem cells. (Source: Gut)
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Jeong, Y., Rhee, H., Martin, S., Klass, D., Lin, Y., Nguyen, L. X. T., Feng, W., Diehn, M. Tags: Oesophagus Source Type: research

Hepatic-specific PPAR{alpha}-FGF21 action in NAFLD
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease in the Western countries affecting 20%–30% of the general population. NAFLD is considered as one of the manifestations of the metabolic syndrome, closely associated with obesity and type 2 diabetes, and may range from steatosis to the more aggressive form of non-alcoholic steatohepatitis (NASH). Long-standing NASH may progress in severe form of liver diseases, such as cirrhosis and hepatocellular carcinoma. Steatosis in the liver is characterised by a large intracytoplasmic or well-defined fat droplets accumulation, displac...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Piccinin, E., Moschetta, A. Tags: Commentary Source Type: research

Early HCC treatment: a future strategy against interferon/miR-484 axis to revert precancerous lesions?
Liver tumours are the sixth most common tumour entity worldwide and the second most common cause of cancer-related deaths. Hepatocellular carcinoma (HCC) is the most frequent liver tumour and is mainly related to viral infections, including HBV and HCV, alcohol consumption, metabolic syndrome and aflatoxin B exposure. Hepatocarcinogenesis is described as a multistep process, which starts mostly by a chronic disease and on the basis of cirrhosis formation. In the recent years, precursor lesions are well described by their morphological characterisation and there is evidence that those precursor lesions are involved in HCC f...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Lechel, A., Gougelet, A. Tags: Commentary Source Type: research

Serrated polyposis syndrome: risk stratification or reduction?
Serrated polyposis syndrome (SPS; formerly ‘hyperplastic polyposis syndrome’) has emerged as by far the most common colorectal polyp syndrome.1 2 SPS is characterised by some combination of large and/or numerous serrated class lesions and is associated with an increased risk of colorectal cancer (CRC).3 A genetic basis for SPS has not yet been discovered, and many cases do not have a family history of SPS or even CRC. Thus, any current definition of SPS must be clinical and based on colonoscopic findings and the pathology of polyps removed during colonoscopy. Most clinicians accept the WHO criteria for diagnosi...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Hassan, C., Repici, A., Rex, D. K. Tags: Commentary Source Type: research

Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities
Introduction IBDs, encompassing Crohn's disease (CD) and UC, are chronic, relapsing and remitting, inflammatory diseases of the GI tract. IBD is emerging as a globally important disease with epidemiological studies showing that there is a significant increase in IBD’s incidence in most regions of the world.1 In high-incidence areas such as North America, disease already affects around 0.6% of the population.1 As low/middle-income countries continue to become more industrialised, an increasing incidence is also expected to occur in areas of the globe where IBD was previously considered rare.2 3 Furthermore, as trends ...
Source: Gut - June 2, 2016 Category: Gastroenterology Authors: Torres, J., Burisch, J., Riddle, M., Dubinsky, M., Colombel, J.-F. Tags: Crohn's disease Leading article Source Type: research

Lack of consensus for usage of {beta}-blockers in end-stage liver disease
The decision of ‘if and when’ to stop non-selective β-blockers (NSBB) at certain stages of end-stage cirrhosis has been debated intensively and has generated a number of studies with various outcomes.1 2 Some studies demonstrated deleterious effects, others improved survival.3 4 However, nobody has looked into how these conflicting findings influence doctors and today’s clinical practice when prescribing NSBB. Our hypothesis is that this ongoing controversy causes an unstandardised usage of NSBB depending on the individual clinician. To test this, we performed a survey consisting of 131 branched ques...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Thorhauge, K. H., Lindvig, K. P., Laleman, W., Angeli, P., Singh, S. P., Krag, A. Tags: PostScript Source Type: research

Algorithm to rule out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multicentre study
Recently, the UK guidelines on variceal bleeding1 and other reports have introduced the role of elastography for the diagnosis of oesophageal varices (OVs).2 3 Development of OVs is likely when the hepatic venous pressure gradient is higher than 10 mm Hg, which defines clinically significant portal hypertension (CSPH). Baveno VI implemented transient elastography (TE) as a tool to rule in CSPH in viral aetiologies and to rule out varices (need of screening endoscopy for varices).4 Furthermore, CSPH has a strong prognostic value in patients with cirrhosis. Recent studies introduced Shear-wave elastography of the l...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Jansen, C., Bogs, C., Verlinden, W., Thiele, M., Möller, P., Görtzen, J., Lehmann, J., Praktiknjo, M., Chang, J., Krag, A., Strassburg, C. P., Francque, S., Trebicka, J. Tags: PostScript Source Type: research