Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells
Conclusions H. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between H. pylori and epithelial cells within the gastric niche. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Wroblewski, L. E., Piazuelo, M. B., Chaturvedi, R., Schumacher, M., Aihara, E., Feng, R., Noto, J. M., Delgado, A., Israel, D. A., Zavros, Y., Montrose, M. H., Shroyer, N., Correa, P., Wilson, K. T., Peek, R. M. Tags: Editor's choice, Pancreatic cancer Helicobacter pylori Source Type: research

Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development
Conclusions KLF5/GATA4/GATA6 may promote GC development by engaging in mutual crosstalk, collaborating to maintain a pro-oncogenic transcriptional regulatory network in GC cells. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Chia, N.-Y., Deng, N., Das, K., Huang, D., Hu, L., Zhu, Y., Lim, K. H., Lee, M.-H., Wu, J., Sam, X. X., Tan, G. S., Wan, W. K., Yu, W., Gan, A., Tan, A. L. K., Tay, S.-T., Soo, K. C., Wong, W. K., Dominguez, L. T. M., Ng, H.-H., Rozen, S., Goh, L.-K., Teh Tags: Pancreatic cancer Stomach Source Type: research

Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel
Conclusions Confirmed LGD in BO has a markedly increased risk of malignant progression. However, the vast majority of patients with community LGD will be downstaged after expert review and have a low progression risk. Therefore, all BO patients with LGD should undergo expert histological review of the diagnosis for adequate risk stratification. (Source: Gut)
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Duits, L. C., Phoa, K. N., Curvers, W. L., ten Kate, F. J. W., Meijer, G. A., Seldenrijk, C. A., Offerhaus, G. J., Visser, M., Meijer, S. L., Krishnadath, K. K., Tijssen, J. G. P., Mallant-Hent, R. C., Bergman, J. J. G. H. M. Tags: Oesophageal cancer Oesophagus Source Type: research

Vitamin D and liver fibrosis: let's start soon before it's too late
Vitamin D is a prohormone that requires sequential enzymatic modification of 25 and 1a-hydroxylation in the liver and kidney respectively, leading to production of calcitriol (1,25(OH)2D3), the active form of vitamin D.1 Several studies have supported the notion that vitamin D, in addition to its classical action of maintaining systemic calcium homoeostasis and bone mineralisation, has non-classical extraskeletal actions including a potential capacity to inhibit fibrosis in various tissues. Murine lung fibroblasts treated with 1,25(OH)2D3, inhibited transforming growth factor (TGF)-β1-induced fibroblast proliferation,...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Nobili, V., Reif, S. Tags: Commentary Source Type: research

Dietary iron supplementation: a proinflammatory attack on the intestine?
Iron deficiency is a global health problem affecting likewise two billion people, and this condition is more prevalent in developing than in industrialised countries. Specifically, in childhood, iron deficiency and subsequent iron deficiency anaemia are considered to negatively affect the development of children causing growth and mental retardation.1 This is due to the fact that iron is essential for oxygen transport as being the central molecule in haemoglobin and referred to the metal's function as an essential compound of many vital enzymes in mitochondrial respiration, metabolism, hormone synthesis and DNA replication...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Weiss, G. Tags: Commentary Source Type: research

What we talk about when we talk about low-grade dysplasia
Nearly a decade has elapsed since initial publication of a multicentre randomised trial of porfimer sodium photodynamic therapy (psPDT) for the treatment of Barrett's oesophagus (BO) containing high-grade dysplasia (HGD).1 With the addition of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) to the therapeutic armamentarium, a seismic shift has now ensued in the treatment landscape of BO-associated mucosal neoplasia. An ever-increasing proportion of patients with BO HGD or T1 oesophageal adenocarcinoma (OAC), opt for endoscopic therapy rather than surgery.2 Durable disease remission is achievable for th...
Source: Gut - April 1, 2015 Category: Gastroenterology Authors: Yachimski, P. Tags: Commentary Source Type: research

Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study
Dear Editor, Increasing evidence suggests that genetic factors play a role in the multifactorial aetiology of liver fibrosis. In their recent paper, Zhao et al1 support this by describing the role of the Jnk1 gene in liver fibrogenesis. Previously, the role of other inflammatory-related genes in the development of liver fibrosis has been described in patients with chronic liver diseases. In patients with chronic hepatitis C, Nalpas et al2 demonstrated a strong association between single nucleotide polymorphisms (SNP) in the interferon gamma receptor 2 (IFNGR2) gene and progression of liver fibrosis. The role of interferon ...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Plompen, E. P. C., Hansen, B. E., Schouten, J. N. L., Murad, S. D., Loth, D. W., Brouwer, W. P., Isaacs, A., Taimr, P., Hofman, A., van Duijn, C. M., Uitterlinden, A. G., Stricker, B. H. C., Leebeek, F. W. G., Janssen, H. L. A. Tags: PostScript Source Type: research

British Society of Gastroenterology guidelines on the diagnosis and management of coeliac disease
The British Society of Gastroenterology (BSG) guidelines1 on diagnosis and management of coeliac disease (CD) contain much useful information, but in our opinion are badly misleading on the important topic of diagnosis and the relative merits of small intestinal biopsy and serology tests. The authors recommend that a duodenal biopsy is essential for diagnosis in all patients and cannot be replaced by serology alone even in a subset of patients. Other studies have now confirmed earlier work showing that using an appropriate cut-off for IgA-class anti-tissue transglutaminase antibody (IgA-tTG), the diagnosis can be made with...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Hill, P., Austin, A., Forsyth, J., Holmes, G. Tags: PostScript Source Type: research

Inhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatment
Recently in Gut, Xiao et al1 detailed an extensive analysis of synergistic inhibition of HCV achieved in various in vitro and in vivo models systems when HCV entry inhibitors were combined with different direct acting antivirals (DAA) and host-targeted antiviral. However, a follow-up commentary by Pawlotsky suggested that ‘there is no unmet clinical need’ for the treatment of HCV that cannot be addressed by the HCV drugs currently approved or in late-stage clinical development.2 Here, we comment on the original study and subsequent commentary. Consistent with the Xiao et al study, we have reported that blocking...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Uprichard, S. L., Sainz, B. Tags: PostScript Source Type: research

Somatic loss of polycystic disease genes contributes to the formation of isolated and polycystic liver cysts
We read with interest the paper by Urribarri et al1 which describes that metalloprotease hyperactivity plays an important role in cyst expansion and that metalloprotease inhibition reduces cyst proliferation. As such, these results help to identify potential drug targets.2 We hypothesise that the expansion and maintenance of the cyst is preceded by mutational events that trigger cytogenesis, and we used genetic analysis to provide additional insight into this process. The majority of polycystic diseases are autosomal dominant disorders where every patient cell possesses one germ line mutation (first hit).3 As somatic secon...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Janssen, M. J., Salomon, J., Cnossen, W. R., Bergmann, C., Pfundt, R., Drenth, J. P. H. Tags: PostScript Source Type: research

Multidirectional clinical profile (MDCP) for the functional GI disorders: first edition
There is a well-established opinion among gastroenterologists from all nations that functional GI disorders and irritable bowel syndrome are the most common diagnoses made in GI clinics and yet represent some of the most challenging patients to manage. The medical mind set is to establish a diagnosis through history, examination and diagnostic tests and to come up with a clear organic explanation for GI disorders. Unfortunately in functional GI disorders, this pathway is often fraught with pitfalls and difficulties and frequently results in endless investigations and fruitless end outcomes for patients in whom no clear org...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Hamdy, S. Tags: PostScript Source Type: research

ATG16L1 contributes to Crohn's disease susceptibility in Koreans: overmuch concern for ethnic difference?
The incidence of Crohn’s disease (CD) increases steadily in Asia, but is still quite low compared with Western countries.1 So far, over 140 susceptibility loci to CD have been identified in Caucasians through genome-wide association studies (GWASs) and meta-analyses.2 Recent GWASs in Korean and Japanese populations identified a few more susceptibility loci, but could not replicate many established CD loci.3 4 A Japanese large scale replication study consisting of 1311 cases and 6585 controls could replicate less than half of 71 CD susceptibility loci identified in Caucasians.5 Particularly, it aroused concern that su...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Yang, S.-K., Ye, B. D., Song, K. Tags: PostScript Source Type: research

GI highlights from the literature
In this study by Nguyen and colleagues, the expression and function of GPR15 on effector T cells in mice and humans was investigated. The authors showed that GPR15 is important for TH1 and TH17... (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis
Conclusions Progression of NASH and NASH-related hepatic mitochondrial dysfunction can be prevented by RYGB. RYGB preserves respiratory chain complex activity, thereby restoring energy output, probably by limiting the amount of oxidative stress and TNF-α. These data suggest that modulation of hepatic mitochondrial function contributes to the favourable effect of RYBG on established NASH. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Verbeek, J., Lannoo, M., Pirinen, E., Ryu, D., Spincemaille, P., Vander Elst, I., Windmolders, P., Thevissen, K., Cammue, B. P. A., van Pelt, J., Fransis, S., Van Eyken, P., Ceuterick-De Groote, C., Van Veldhoven, P. P., Bedossa, P., Nevens, F., Auwerx, J Tags: Hepatology Source Type: research

Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study
Conclusions Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Seto, W.-K., Hui, A. J., Wong, V. W.-S., Wong, G. L.-H., Liu, K. S.-H., Lai, C.-L., Yuen, M.-F., Chan, H. L.-Y. Tags: Hepatology Source Type: research

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats
Conclusions This study provides compelling experimental evidence indicating that PEDF could be a novel therapeutic agent worthy of assessment in portal hypertension and cirrhosis. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Mejias, M., Coch, L., Berzigotti, A., Garcia-Pras, E., Gallego, J., Bosch, J., Fernandez, M. Tags: Hepatology Source Type: research

Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study
Conclusions These are the first results indicating that ABO blood type-B as well as FUT2 non-secretor status are common population-wide risk factors for developing chronic pancreatitis. They also imply that, even within the reference range, elevated lipase activities may indicate subclinical pancreatic injury in asymptomatic subjects. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Weiss, F. U., Schurmann, C., Guenther, A., Ernst, F., Teumer, A., Mayerle, J., Simon, P., Volzke, H., Radke, D., Greinacher, A., Kuehn, J.-P., Zenker, M., Volker, U., Homuth, G., Lerch, M. M. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
Conclusions The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Yu, J., Wu, W. K. K., Li, X., He, J., Li, X.-X., Ng, S. S. M., Yu, C., Gao, Z., Yang, J., Li, M., Wang, Q., Liang, Q., Pan, Y., Tong, J. H., To, K. F., Wong, N., Zhang, N., Chen, J., Lu, Y., Lai, P. B. S., Chan, F. K. L., Li, Y., Kung, H.-F., Yang, H., Wa Tags: Open access, Colon cancer Source Type: research

Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics
Conclusions This fluorescence virus-guided viable CTC capturing method provides a non-invasive alternative to tissue biopsy or surgical resection of primary tumours for companion diagnostics. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Shigeyasu, K., Tazawa, H., Hashimoto, Y., Mori, Y., Nishizaki, M., Kishimoto, H., Nagasaka, T., Kuroda, S., Urata, Y., Goel, A., Kagawa, S., Fujiwara, T. Tags: Colon cancer GI cancer Source Type: research

Mechanisms of activation of mouse and human enteroendocrine cells by nutrients
Conclusions Specific nutrient receptors associate with distinct activation pathways within EEC. These may provide discrete, complementary pharmacological targets for intervention in obesity and type II diabetes. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Symonds, E. L., Peiris, M., Page, A. J., Chia, B., Dogra, H., Masding, A., Galanakis, V., Atiba, M., Bulmer, D., Young, R. L., Blackshaw, L. A. Tags: Open access Neurogastroenterology Source Type: research

Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity
Conclusions The development of oesophageal hyperalgesia is prevented by physiologically increasing parasympathetic tone. This effect is pharmacologically blocked with atropine, providing evidence that the PNS influences the development of oesophageal pain hypersensitivity. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Botha, C., Farmer, A. D., Nilsson, M., Brock, C., Gavrila, A. D., Drewes, A. M., Knowles, C. H., Aziz, Q. Tags: Neurogastroenterology Source Type: research

Dyspepsia and weight loss in a 47-year-old man
A 47-year-old man presented with mild epigastric pain, dyspepsia and 4 kg weight loss for the last 2 months. There was no history of fever, GI bleeding, cough or pertinent past illnesses or surgery. Physical examination was unremarkable. Routine laboratory tests were within the normal range except for mild anaemia (haemoglobin concentration 11.4 g/dL) and increased erythrocyte sedimentation rate (54 mm/h). ECG and chest X-ray were normal, and serology of HIV, HBV and HCV were negative. Upper endoscopy showed several multilobulated subepithelial lesions (SEL) in the gastric body, cardia and antrum with n...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Ramchandani, M., Lakhtakia, S., Galasso, D., Baron, T., Sekaran, A., Reddy, D. N. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Caspase-8 controls the gut response to microbial challenges by Tnf-{alpha}-dependent and independent pathways
Conclusions Together, our data demonstrate an essential role for caspase-8 in maintaining the gut barrier in response to mucosal pathogens by permitting inflammatory shedding and preventing necroptosis of infected cells. These data suggest that therapeutic strategies targeting the cell death machinery represent a promising new option for the treatment of inflammatory and infective enteropathies. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Gunther, C., Buchen, B., He, G.-W., Hornef, M., Torow, N., Neumann, H., Wittkopf, N., Martini, E., Basic, M., Bleich, A., Watson, A. J. M., Neurath, M. F., Becker, C. Tags: Open access Small bowel Source Type: research

The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation
Conclusions These findings point to uPAR as an essential component of intestinal macrophage functions and unravel a new potential target to control mucosal inflammation in IBD. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Genua, M., D'Alessio, S., Cibella, J., Gandelli, A., Sala, E., Correale, C., Spinelli, A., Arena, V., Malesci, A., Rutella, S., Ploplis, V. A., Vetrano, S., Danese, S. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Early endoscopic, laboratory and clinical predictors of poor disease course in paediatric ulcerative colitis
Conclusions Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Schechter, A., Griffiths, C., Gana, J. C., Shaoul, R., Shamir, R., Shteyer, E., Bdolah-Abram, T., Ledder, O., Turner, D. Tags: Ulcerative colitis Inflammatory bowel disease Source Type: research

Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis
Objective Over 100 ulcerative colitis (UC) loci have been identified by genome-wide association studies (GWASs) primarily in Caucasians (CEUs). Many of them have weak effects on disease susceptibility, and the bulk of the heritability cannot be ascribed to these loci. Very little is known about the genetic background of UC in non-CEU groups. Here we report the first GWAS on UC in a genetically distinct north Indian (NI) population. Design A genome-wide scan was performed on 700 cases and 761 controls. 18 single-nucleotide polymorphisms (SNPs) (p
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Juyal, G., Negi, S., Sood, A., Gupta, A., Prasad, P., Senapati, S., Zaneveld, J., Singh, S., Midha, V., van Sommeren, S., Weersma, R. K., Ott, J., Jain, S., Juyal, R. C., Thelma, B. K. Tags: Ulcerative colitis Inflammatory bowel disease Source Type: research

Abnormal fibre usage in UC in remission
Conclusions Gut fermentation of NSP and starch is diminished in patients with UC. This cannot be explained by abnormal gut transit and was not corrected by increasing RS/WB intake, and may be due to abnormal functioning of the gut microbiota. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12614000271606. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: James, S. L., Christophersen, C. T., Bird, A. R., Conlon, M. A., Rosella, O., Gibson, P. R., Muir, J. G. Tags: Inflammatory bowel disease Source Type: research

Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis
Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Cao, Q., Didelot, X., Wu, Z., Li, Z., He, L., Li, Y., Ni, M., You, Y., Lin, X., Li, Z., Gong, Y., Zheng, M., Zhang, M., Liu, J., Wang, W., Bo, X., Falush, D., Wang, S., Zhang, J. Tags: Open access, Stomach and duodenum Helicobacter pylori Source Type: research

CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis
Conclusions CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy. (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Hayakawa, Y., Jin, G., Wang, H., Chen, X., Westphalen, C. B., Asfaha, S., Renz, B. W., Ariyama, H., Dubeykovskaya, Z. A., Takemoto, Y., Lee, Y., Muley, A., Tailor, Y., Chen, D., Muthupalani, S., Fox, J. G., Shulkes, A., Worthley, D. L., Takaishi, S., Wang Tags: Gastrointestinal hormones, Pancreatic cancer Stomach Source Type: research

Small intestinal permeability in patients with eosinophilic oesophagitis during active phase and remission
Background Eosinophilic oesophagitis (EoE) is presumed to be an isolated oesophageal disease; yet other allergic diseases associated with eosinophilic infiltration of target tissues, such as asthma and eczema, show perturbed functions of other sites that may be involved in the diathesis of allergy modulation. Aim To analyse small intestinal permeability in patients with active EoE and in a separate group of patients in remission. Methods Small bowel permeability was determined using a dual sugar method by calculating lactulose:mannitol (L:M) ratio in 17 patients who met consensus criteria for active EoE (>15 eos/HPF) ...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Katzka, D. A., Geno, D. M., Blair, H. E., Lamsam, J. L., Alexander, J. A., Camilleri, M. Tags: Oesophagus Source Type: research

Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites
Introduction Acute renal failure (ARF) is a common complication in patients with decompensated cirrhosis. The traditional diagnostic criteria of renal failure in these patients were proposed in 19961 and have been refined in subsequent years.2 According to these criteria, ARF is defined as an increase in serum creatinine (sCr) of ≥50% from baseline to a final value>1.5 mg/dL (133 µmol/L). However, the threshold value of 1.5 mg/dL (133 µmol/L) sCr to define renal failure in patients with decompensated cirrhosis has been challenged.3 4 In addition, the timeframe to distinguish acute from...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Angeli, P., Gines, P., Wong, F., Bernardi, M., Boyer, T. D., Gerbes, A., Moreau, R., Jalan, R., Sarin, S. K., Piano, S., Moore, K., Lee, S. S., Durand, F., Salerno, F., Caraceni, P., Kim, W. R., Arroyo, V., Garcia-Tsao, G. Tags: Cirrhosis, Editor's choice Leading article Source Type: research

Circulating tumour cells go green
This study is published in Gut.1 Shigeyasu et al1 capture, image and characterise epithelial... (Source: Gut)
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Hoffman, R. M. Tags: Commentary Source Type: research

Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue?
Treatment cessation is one of the few challenges left to clinicians to deal with after the marketing and widespread use of third generation oral analogues (nucleos(t)ide analogue (NUC)), entecavir (ETV) and tenofovir (TDF) for the treatment of HBeAg negative chronic hepatitis B (CHB). Treatment efficacy is in fact unquestioned as more than 95% of patients, including NUC experienced and resistant ones, achieve complete suppression of viral replication and improvement of hepatic inflammation and fibrosis within the first 5 years of treatment.1–3 As a consequence, in a majority of patients, progression to cirrhosis...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Lampertico, P. Tags: Commentary Source Type: research

Gastric bypass surgery in NASH: a major modulator of hepatic mitochondrial dysfunction
Non-alcoholic fatty liver disease (NAFLD), the hepatic counterpart of metabolic syndrome, has gained increasing recognition worldwide as a component of the obesity and type 2 diabetes pandemic. The spectrum of NAFLD ranges from simple fatty liver with benign prognosis, to non-alcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis, thereby increasing morbidity and mortality. According to the traditional view, hepatic fat accumulation represents the prerequisite for hepatocyte injury to develop, whereas cytokines, adipokines, bacterial endotoxin, mitochondrial dysfunction and/or endoplasmic reti...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Baraille, F., Guilmeau, S., Postic, C. Tags: Commentary Source Type: research

Boosting pigment epithelial-derived factor: a promising approach for the treatment of early portal hypertension
Portal hypertension (PHT) is a heterogeneous clinical entity which develops in patients with cirrhosis. It is responsible for many of the complications that occur in cirrhosis, including gastroesophageal varices, hepatorenal syndrome, ascites, hepatic encephalopathy and hypersplenism.1 There are three principal factors responsible for the development of PHT, namely (1) purely mechanical obstruction resulting from hepatic fibrosis and regenerative nodules; (2) contraction of sinusoidal and perisinusoidal contractile cells due to an imbalance between intrahepatic vasoconstrictory and vasodilatory mediators and (3) splanchnic...
Source: Gut - March 6, 2015 Category: Gastroenterology Authors: Vespasiani-Gentilucci, U., Rombouts, K. Tags: Open access Commentary Source Type: research

Authors' response to the letter: Liver resection for patients with hepatocellular carcinoma and macrovascular invasion, multiple tumours or portal hypertension by Zhong et al
We appreciate the opportunity to comment on the controversial issues surrounding treatment options for patients with hepatocellular carcinoma. In the field of surgery or interventional radiology it is common to emphasise technical feasibility and early morbidity/mortality rather than medium/long-term survival. Expanding life expectancy of the patients in comparison with that offered by other treatments, or even no treatment, is the goal of therapy. In our review1 and in practice guidelines2 3 the recommendations were based on robust data from prospective studies, preferably randomised, in the target population that had the...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Bruix, J., Gores, G., Mazzaferro, V. Tags: PostScript Source Type: research

Liver resection for patients with hepatocellular carcinoma and macrovascular invasion, multiple tumours, or portal hypertension
This article recommended palliative treatments for patients with hepatocellular carcinoma (HCC) involving macrovascular invasion, multiple tumours, or portal hypertension. With better patient selection and improvement of perioperative care, liver resection (LR) offers the most consistent and clinically meaningful long-term survival in HCC over the past 20 years, which has been documented by both Eastern and Western centres.2 3 However, Western official guidelines do not recommend LR for treating intermediate and advanced stage HCC.4 5 Here, we systematically searched PubMed database for studies investigating the safet...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Zhong, J.-H., Ke, Y., Wang, Y.-Y., Li, L.-Q. Tags: PostScript Source Type: research

Author response: linking lifestyle and microbes
Marlicz and Loniewski1 offer complementary comments regarding the design and execution of our study of exercise and associated dietary extremes on gut microbial diversity.2 They expand on some of the caveats already raised by us. First, we were careful not to transmute correlation into causation. As implied in the title of our study and explicit in our report, we acknowledged and recorded the dietary changes that accompany exercise, particularly in professional athletes. A further study has been designed to control for and examine the separate contributions of diet and exercise in a prospective manner in non-professional a...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Shanahan, F., Clarke, S. F., Murphy, E. F., O'Sullivan, O., Cotter, P. Tags: PostScript Source Type: research

The effect of exercise and diet on gut microbial diversity
We have read with great interest the study by Clarke et al1 who in a very elegant and sophisticated manner documented the increase in gut microbial diversity in association with exercise and dietary extremes in professional rugby players. The observed microbial shifts were accompanied by lower inflammatory and healthier metabolic profiles among athletes. Significantly higher proportions of the genus Akkermansia muciniphila in athletes as well as in low Body Mass Index control group were found. As previously shown, the presence of these bacteria in the human GI tract has been associated with improved metabolic profiles, pos...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Marlicz, W., Loniewski, I. Tags: PostScript Source Type: research

Species-specific and pathotype-specific binding of bacteria to zymogen granule membrane glycoprotein 2 (GP2)
Dear Editor, With interest we read the paper by Juste et al1 proposing the amount of zymogen-granule membrane glycoprotein 2 (GP2) on the surface of intestinal bacteria as a Crohn's disease (CD) marker. Indeed, a decreased GP2 level was found on microbes in patients with CD as compared to those of healthy controls. GP2 is a homologue to the urinary Tamm–Horsefall protein demonstrating an antimicrobial function by binding type 1-fimbriated uropathogenic Escherichia coli (UPEC). Likewise, GP2 seems to interact with intestinal bacteria as a specific receptor of bacterial type-1 fimbriae (FimH) on intestinal microfold ce...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Schierack, P., Rodiger, S., Kolenda, R., Hiemann, R., Berger, E., Grzymajło, K., Swidsinski, A., Juretzek, T., Meissner, D., Mydlak, K., Reinhold, D., Nolan, L. K., Roggenbuck, D. Tags: PostScript Source Type: research

Importance of defining loss of response before therapeutic drug monitoring
Dear Sir, I read with interest the study by Steenholdt et al1 which concluded that individualised infliximab therapy was more cost effective compared with empirical dose escalation in Crohn's disease (CD) patients who developed secondary non-response to infliximab. The study methodology has a number of questions that require attention. First, 80% of the patients recruited for the study had non-fistulising disease, and the study entry criterion for them was having a Crohn's Disease Activity Index (CDAI) score of ≥220. Furthermore, the endpoint for clinical response for them was defined as CDAI reduction of ≥70 points....
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Tan, M. Tags: PostScript Source Type: research

Paradoxical responses of plasma glucagon and bile acid levels after duodenal nutrient exclusion
Dear Sir, We read with interest the article by Habegger et al1 who demonstrated that duodenal nutrient exclusion using duodenal endoluminal sleeve (DES) improves metabolic syndrome and stimulates intestinal villus hyperplasia, especially the bypassed duodenum, in a rodent model of type 2 diabetes mellitus. There were three intriguing results. First, with regard to DES improving glucose homeostasis, the area under curve analysis showed that both sham-operated and the DES group had statistically significant improvements in glucose homeostasis. Nevertheless, since the pair-fed group had received the same sham operation, it is...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Chen, P.-C., Inui, A., Chen, C.-Y. Tags: PostScript Source Type: research

GI highlights from the literature
This study by Goodrich and colleagues assessed whether specific bacterial taxa within the gut microbiome were heritable and could be related to host body mass index (BMI). They also looked at whether predicted... (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

MicroRNAs: new players in IBD
MicroRNAs (miRNAs) are small non-coding RNAs, 18–23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Kalla, R., Ventham, N. T., Kennedy, N. A., Quintana, J. F., Nimmo, E. R., Buck, A. H., Satsangi, J. Tags: GUT Recent advances in basic science, Open access Source Type: research

Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection
Objective To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV. Methods This nationwide cohort study screened 293 480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12 384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24 768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute ...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Hsu, Y.-C., Ho, H. J., Huang, Y.-T., Wang, H.-H., Wu, M.-S., Lin, J.-T., Wu, C.-Y. Tags: Hepatology Source Type: research

Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C
Conclusions Our results provide a rationale for the development of antiviral strategies combining entry inhibitors with DAAs or HTAs by taking advantage of synergy. The uncovered combinations provide perspectives for efficient strategies to prevent liver graft infection and novel interferon-free regimens. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Xiao, F., Fofana, I., Thumann, C., Mailly, L., Alles, R., Robinet, E., Meyer, N., Schaeffer, M., Habersetzer, F., Doffoel, M., Leyssen, P., Neyts, J., Zeisel, M. B., Baumert, T. F. Tags: Open access Hepatology Source Type: research

Effects of HDV infection and pegylated interferon {alpha} treatment on the natural killer cell compartment in chronically infected individuals
Conclusions We describe in detail how HDV infection, and IFNα treatment of this infection, affects the NK cell compartment and what consequences this has for the functional capacity of NK cells. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Lunemann, S., Malone, D. F. G., Grabowski, J., Port, K., Beziat, V., Bremer, B., Malmberg, K.-J., Manns, M. P., Sandberg, J. K., Cornberg, M., Ljunggren, H.-G., Wedemeyer, H., Bjorkstrom, N. K. Tags: Hepatology Source Type: research

Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect
Conclusions These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Wang, X., Yang, Y., Huycke, M. M. Tags: Open access, Colon cancer Gut microbiota Source Type: research

Abdominal pain following percutaneous mitral valve repair (MitraClip)
Clinical presentation An 81-year-old man underwent percutaneous mitral valve repair (MitraClip) due to severe symptomatic mitral valve regurgitation. Coronary heart disease was excluded prior to mitral valve repair. Approximately 8 h after the uneventful and successful intervention, the patient presented with progressive abdominal pain, in particular tenderness in the right upper quadrant with guarding. Laboratory tests did not reveal any acute alterations; serum lactate was 2.4 mmol/L. Bedside ultrasonography showed a distended ascending colon with a pronounced hyperechoic large bowel wall (figure 1A). Native CT...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Neesse, A., Nimphius, W., Schoppet, M., Gress, T. M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD
Background Bacteria play a role in the onset and perpetuation of intestinal inflammation in IBD. Compositional alterations may also change the metabolic capacities of the gut bacteria. Objective To examine the metabolic activity of the microbiota of patients with Crohn's disease (CD), UC or pouchitis compared with healthy controls (HC) and determine whether eventual differences might be related to the pathogenesis of the disease. Methods Faecal samples were obtained from 40 HC, 83 patients with CD, 68 with UC and 13 with pouchitis. Disease activity was assessed in CD using the Harvey–Bradshaw Index, in UC using the...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: De Preter, V., Machiels, K., Joossens, M., Arijs, I., Matthys, C., Vermeire, S., Rutgeerts, P., Verbeke, K. Tags: Crohn's disease Inflammatory bowel disease Source Type: research