Showing papers in "Journal of Gastroenterology and Hepatology in 2017"

What is gluten

Abstract: Gluten is the main storage protein of wheat grains. Gluten is a complex mixture of hundreds of related but distinct proteins, mainly gliadin and glutenin. Similar storage proteins exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as “gluten.” The objective was to discuss the biochemical and functional properties of the gluten proteins, including structure, sources, and dietary intakes. Literature was reviewed from food science and nutrition journals. The gluten protein networks vary because of different components and sizes, and variability caused by genotype, growing conditions, and technological processes. The structures and interactions of this matrix contribute to the unique properties of gluten. The resulting functions are essential to determining the dough quality of bread and other baked products. Gluten is heat stable and has the capacity to act as a binding and extending agent and is commonly used as an additive in processed foods for improved texture, moisture retention, and flavor. Gliadin contains peptide sequences that are highly resistant to gastric, pancreatic, and intestinal proteolytic digestion in the gastrointestinal tract. The average daily gluten intake in a Western diet is thought to be 5–20 g/day and has been implicated in several disorders. Gluten containing grains (wheat, rye, barley, and oats) are important staple foods. Gluten is among the most complex protein networks and plays a key role in determining the rheological dough properties.

Prebiotic inulin-type fructans and galacto-oligosaccharides: definition, specificity, function, and application in gastrointestinal disorders.

Abstract: Prebiotics are non-digestible selectively fermented dietary fibers that specifically promote the growth of one or more bacterial genera in the gastrointestinal tract and thus provide health benefit to the host. The two most investigated prebiotics being the inulin-type fructans and galacto-oligosaccharides. Prebiotic specificity is mediated through species-specific gene clusters within saccharolytic bacteria controlled by signaling sensors for various substrates. Prebiotic health benefits are attributed to immune regulation and bacterial metabolite production. In humans, prebiotic supplementation leads to increased growth of specific gut microbiota (e.g., bifidobacteria), immune modulation, and depending on the bacterial augmentation, short-chain fatty acid production. Irritable bowel syndrome and Crohn's disease are gastrointestinal disorders associated with reductions in some gut bacteria and greater mucosal inflammation. Prebiotic supplementation studies have shown some promise at low doses for modulation of the gut bacteria and reduction of symptoms in IBS; however, larger doses may have neutral or negative impact on symptoms. Studies in Crohn's disease have not shown benefit to bacterial modulation or inflammatory response with prebiotic supplementation. Dietary restriction of fermentable carbohydrates (low FODMAP diet), which restricts some naturally occurring prebiotics from the diet, has shown efficacy in improving symptoms in irritable bowel syndrome, but it lowers the numbers of some key gut microbiota. Further research is required on the effect of prebiotics in gastrointestinal disorders and, in particular, on their use in conjunction with the low FODMAP diet.

Proton pump inhibitors: risks of long-term use

Abstract: Proton pump inhibitors are among the most commonly prescribed classes of drugs, and their use is increasing, in particular for long-term treatment, often being over-prescribed and used for inappropriate conditions. In recent years, considerable attention has been directed towards a wide range of adverse effects, and even when a potential underlying biological mechanism is plausible, the clinical evidence of the adverse effect is often weak. Several long-term side effects have been investigated ranging from interaction with other drugs, increased risk of infection, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia. The most recent literature regarding these adverse effects and their association with long-term proton pump inhibitor treatment is reviewed, and the mechanisms through which these possible complications might develop are discussed.

Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B.

Abstract: Background and Aims Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. The risk of HBV-related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis. Methods We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non-alcoholic fatty liver disease-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3, and PPARG). Results Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52–34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30–11.84; P = 0.013) were independent factors predicting HCC development. Conclusions Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-fold. The risk of HBV-related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.

FODMAPs: food composition, defining cutoff values and international application.

Abstract: The low-FODMAP diet is a new dietary therapy for the management of irritable bowel syndrome that is gaining in popularity around the world. Developing the low-FODMAP diet required not only extensive food composition data but also the establishment of "cutoff values" to classify foods as low-FODMAP. These cutoff values relate to each particular FODMAP present in a food, including oligosaccharides (fructans and galacto-oligosaccharides), sugar polyols (mannitol and sorbitol), lactose, and fructose in excess of glucose. Cutoff values were derived by considering the FODMAP levels in typical serving sizes of foods that commonly trigger symptoms in individuals with irritable bowel syndrome, as well as foods that were generally well tolerated. The reliability of these FODMAP cutoff values has been tested in a number of dietary studies. The development of the techniques to quantify the FODMAP content of foods has greatly advanced our understanding of food composition. FODMAP composition is affected by food processing techniques and ingredient selection. In the USA, the use of high-fructose corn syrups may contribute to the higher FODMAP levels detected (via excess fructose) in some processed foods. Because food processing techniques and ingredients can vary between countries, more comprehensive food composition data are needed for this diet to be more easily implemented internationally.

Alterations of gut microbiota in patients with irritable bowel syndrome: A systematic review and meta-analysis.

Abstract: Background and Aims Alterations of gut microbiota were assumed to be the etiology and pathogenesis of irritable bowel syndrome (IBS) in some studies. However, alterations of gut microbiota in IBS patients had not been systematically assessed with a meta-analysis. We performed a mate-analysis to explore and compare the alterations of gut microbiota in IBS patients from China and other regions around the world. Methods Case-control studies detecting gut microbiota in IBS patients were identified through English and Chinese databases. The standardized mean difference (SMD) with 95% confidence interval (CI) of bacterial counts was calculated. Results Ten studies from China and seven studies from other regions around the world were included in our study. As compared to healthy controls, the SMDs of Bifidobacteria, Lactobacillus, Escherichia Coli and Enterobacter in Chinese IBS patients were -1.42 (CI: -2.10, -0.75), -0.91 (95% CI: -1.31, -0.52), 0.83 (95% CI: 0.26, 1.40) and 0.57 (95% CI: 0.33, 0.82), respectively. But the SMDs of Bacteroides and Enterococcus were found no significant differences in Chinese IBS patients. However, the SMDs of Bifidobacteria and Bacteroides in IBS patients from other regions were -0.76 (CI: -1.43, -0.09) and 1.17 (CI: 0.00, 2.35), while the SMDs of Lactobacillus, Escherichia Coli, Enterobacter and Enterococcus were found no significant differences. Conclusions There were alterations of gut microbiota in IBS patients and it implied that alterations of gut microbiota might be involved in the pathogenesis of IBS. However, the species-specific alterations of gut microbiota were different between IBS patients from China and other regions.

ALBI and PALBI grade predict survival for HCC across treatment modalities and BCLC stages in the MELD Era.

Abstract: Background and Aim The severity of liver dysfunction in hepatocellular carcinoma (HCC) is often estimated with Child–Turcotte–Pugh (CTP) classification or model for end-stage liver disease (MELD) score. We aim to investigate the performance of albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grade, which are recently reported to be simple and objective measurements for liver reserve in HCC. Methods Between 2002 and 2014, consecutive 3182 HCC patients were enrolled to follow up their survival. The area under receiver-operator-characteristic curve (AUC) was calculated to test the discriminatory powers over 1-year, 3-year, and 5-year survival. Results Significant survival differences were found across all ALBI and PALBI grades (both P < 0.001). The majority (73%) of patients were CTP class A. Within CTP class A, ALBI revealed two prognostic groups while PALBI segregated three prognostic groups. The PABLI grade also identified three different survival groups for patients undergoing resection, ablation, and chemoembolization. Both ALBI and PALBI grade were capable of discerning survival among different HCC stages. The PALBI grade had significantly higher AUC compared with CTP classification and ALBI grade at 1, 3, and 5 years. For CTP class A patients, the PALBI grade was also associated with significantly higher AUC compared with ALBI grade at 1-year and 3-year intervals. The MELD score has the lowest AUC compared with other systems. Conclusions Both ALBI and PALBI grade are adequate models to assess liver dysfunction in HCC. The PALBI grade is consistently better in all patients, in patients with minimally decreased liver function, and in patients receiving different aggressive therapies.

Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.

Abstract: Background/Aim Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. Methods C57BL/6 J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 hrs prior to euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction proteins (TJ), TLRs and TNFα were assessed. Caco-2 monolayers with/without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Results Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic TLR mRNA expression and TNFα protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice. Conclusions Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury.

Eosinophilic gastroenteritis: A state-of-the-art review.

Abstract: Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible.

Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

Abstract: Background and Aim There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. Methods A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). Results Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7–14.7), 8.8 (7.1–12.1), and 7.6 (6.3–10.3) kPa, respectively (P 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7–15.2), 9.2 (7.3–12.1), and 7.7 (6.3–10.1) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). Conclusion These results suggest that early improvement of liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis.

Comparison of the Rome IV and Rome III criteria for IBS diagnosis: A cross-sectional survey

Abstract: Background and Aims The aims of this study were to investigate the proportion of clinical irritable bowel syndrome (IBS) at a tertiary hospital in China, to compare the Rome III and Rome IV criteria with regard to IBS diagnosis, to describe the agreement between the Rome III and Rome IV criteria, and to identify differences between Rome IV-positive and -negative IBS patients. Methods A cross-sectional survey was performed among outpatients in the gastrointestinal (GI) department of a tertiary hospital. The patients were categorized as having IBS using Rome III and Rome IV criteria. Results In total, 1,376 (91.7%) patients completed a GI symptom questionnaire. Among them, 352 were suspected of having IBS and 175 were diagnosed with IBS using the Rome III or Rome IV criteria. In particular, 170 (12.4%) patients were diagnosed with IBS using the Rome III criteria, and 84 (6.1%) patients were diagnosed using the Rome IV criteria. Rome IV IBS patients experienced more pain symptoms (P<0.01) and showed higher IBS severity scores. In contrast, no significant differences were noted for demographic characteristics, stool frequency, IBS subtype, disease course, operation history or GI infection history between Rome IV IBS patients and IBS patients not diagnosed with the Rome IV criteria. Conclusions Rome IV-positive IBS patients represented approximately half of Rome III-positive IBS patients at a tertiary hospital in China. More specifically, Rome IV-positive IBS was mainly a subgroup of Rome III-positive IBS with more serious symptoms.

Use of the low-FODMAP diet in inflammatory bowel disease

Abstract: Irritable bowel syndrome (IBS)-like symptoms are not uncommon in patients with quiescent inflammatory bowel disease (IBD). While gluten-free diet is applied by patients, there are no reported interventional studies. The low-FODMAP diet, on the other hand, has efficacy similar to that seen in patients with IBS in three unblinded or observational studies of IBD cohorts who had well-controlled inflammatory disease and in one small randomized cross-over study. FODMAP intake by patients with IBD is not elevated, and, in one study, fructan intakes were lower in patients with Crohn's disease than in controls. There is no clear relationship between the level of FODMAP intake and intestinal inflammation. The risk of compromising nutritional status with a restrictive diet must be seriously considered especially as under-nutrition is already common in this patient population. The effects of FODMAPs on the gut microbiota of patients with Crohn's disease mimic that in IBS, with a balance between prebiosis from the addition of FODMAPs and loss of prebiosis from their reduction. As undernutrition is common in IBD, the use of restrictive diets should be supervised by a dietitian. Thus, low-FODMAP diet is a viable option for IBS-like symptoms but should be carefully supervised to mitigate risk.

The long noncoding RNA‐ROR promotes the resistance of radiotherapy for human colorectal cancer cells by targeting the p53/miR‐145 pathway

Abstract: Background and Aim Long intergenic noncoding RNAs (lincRNAs) have critical roles in elevating efficacy of anticancer therapy and tumor progression. Recent studies show that Regulator of Reprogramming (ROR) is aberrantly expressed in several types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a standard preoperative treatment. However, a considerable number of CRCs are resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in radiotherapy for CRC and detected the underlying molecular mechanism. Methods Real-time polymerase chain reaction was employed to quantify the expression level of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and apoptosis assays were used to confirm the radiotherapy-mediated effects by lincRNA-ROR altered expression. The direct impact of lincRNA-ROR on the expression of p53/miR-145 by loss-of-function and gain-of-function strategy was also analyzed. A xenograft mouse model was used to evaluate the role of linc-ROR in CRC treatment. Results We discovered that lincRNA-ROR was upregulated in CRC cell lines and tissue samples. We further showed that knockdown of lincRNA-ROR enhanced the sensitivity to radiotherapy for CRC by inhibiting cell viability and promoting apoptosis. Activity of the p53/miR-145 pathway may help explain the role of lincRNA-ROR for stress-induced regulation in CRC therapy. Combined specific knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model resulted in a significant reduction in the tumor growth. Conclusion LincRNA-ROR decreases sensitivity to radiotherapy via the negative regulation of p53/miR-145 and may represent a potential target for the treatment of CRC.

Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon.

Abstract: Background and Aim Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. Methods This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. Results There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. Conclusion Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.

How to institute the low-FODMAP diet.

Abstract: A diet low in poorly absorbed, fermentable, short chain carbohydrates (FODMAPs) is an effective strategy to manage symptoms of irritable bowel syndrome (IBS). The diet has gained traction since its original description in Australia 10 years ago and is now an internationally accepted dietary management strategy for IBS. Randomized controlled trials have raised the profile of the low-FODMAP diet to become a viable first-line therapy for IBS, when implemented under a dietitian's guidance. Importantly, the diagnosis of IBS should be confirmed before commencement of the dietary approach. The skill set of the dietitian is then paramount to the success of the diet. Experience in gastrointestinal disorder management, consideration of symptom types, severity, baseline FODMAP intake, and overall nutritional content and meal pattern are vital in the assessment of the patient. If a strict low-FODMAP diet is deemed necessary, it should only be for an initial period of 4 to 6 weeks. Research suggests that a strict long-term, low-FODMAP diet may negatively impact intestinal microbiome. After the initial strict period, follow up with the dietitian should be conducted to achieve the overall goal—a relaxed FODMAP restriction that enables inclusion of prebiotic FODMAPs while still maintaining symptom relief. The diet will be effective in the vast majority of patients. For those in which it fails, FODMAPs should be reintroduced to the diet, and other dietary (or non-dietary) approaches should be considered.

Hepatic stellate cells secreting WFA+-M2BP: Its role in biological interactions with Kupffer cells

Abstract: Background and Aim Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA+-M2BP was identified as a ligand of Mac-2, the function of WFA+-M2BP in hepatic fibrosis remains unclear. Methods Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA+-M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA+-M2BP in activated HSCs was evaluated using immunoblot analysis. Results Numbers of WFA+-M2BP-positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA+-M2BP levels between fibrosis stages F0 and F1–2 (P = 0.012) and between fibrosis stages F1–2 and F3–4 (P < 0.001). HSCs were the source of WFA+-M2BP secretion in in vitro cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX-2 also secreted WFA+-M2BP. Histologically, tissue sections showed that WFA+-M2BP was located in Mac-2-expressing KCs. In vitro assays showed that exogenous WFA+-M2BP stimulation enhanced Mac-2 expression in KCs and that HSCs co-cultured with KCs increased α-smooth muscle actin expression. Finally, Mac-2-depleted KCs with short interfering RNA had reduced α-smooth muscle actin expression following co-culturing with HSCs. Conclusions WFA+-M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic.

Frequency and risk factors of functional gastro-intestinal disorders in a rural Indian population.

Abstract: Background and Aim As best estimates on functional gastrointestinal disorders (FGIDs) prevalence are expected from community studies, which are scanty from Asia, we evaluated the prevalence and risk factors of FGIDs in a rural Indian community. Methods House-to-house survey was undertaken by trained interviewers using translated-validated Rome III and hospital anxiety and depression questionnaires. Result Among 3426 subjects ≥ 18 years old from 3 villages in Uttar Pradesh, 84% participated, of whom 80% were finally analyzed. Of these 2774 subjects (age 38.4 ± 16.5 years, 1573 [56.7%] male), 2654 [95.7%] were vegetarian and 120 [4.3%] non-vegetarian. Socioeconomic classes were upper (16.7%), upper middle (15.1%), lower middle (22%), upper lower (22.2%), and lower (24%) using Prasad's Classification; 603 (21.7%) had FGIDs (413 [14.9%] dyspepsia, 75 [2.7%] irritable bowel syndrome (IBS) and 115 [4.1%] dyspepsia-IBS overlap), by Rome III criteria. In subjects with dyspepsia, 49/528 (9%) had epigastric pain, 141 (27%) postprandial distress syndromes (EPS, PDS) and 338 (64%) EPS-PDS overlap. IBS was more often diarrhea than constipation-predominant subtype. On univariate analysis, chewing tobacco, aerated drink, tea/coffee, disturbed sleep, vegetarianism, and anxiety parameters and presence of dyspepsia predicting occurrence of IBS were associated with FGIDs. On multivariate analysis, chewing tobacco, aerated soft drink, tea/coffee, vegetarianism, anxiety parameters, and presence of dyspepsia predicting IBS were significant. Conclusion Functional gastrointestinal disorders, particularly dyspepsia-IBS overlap, are common in rural Indian population; the risk factors included chewing tobacco, aerated soft drink, tea/coffee, vegetarian diet, disturbed sleep, anxiety, and dyspepsia predicting occurrence of IBS.

Non-coeliac gluten sensitivity

Abstract: Irritable bowel syndrome-like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non-coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non-coeliac gluten sensitivity is excluded by blinded placebo-controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self-reported non-coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem.

Fecal neutrophil gelatinase-associated lipocalin as a biomarker for inflammatory bowel disease

Abstract: Background and Aim Accurate, noninvasive biomarkers are needed to diagnose and monitor inflammatory bowel disease (IBD). Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin 2, is expressed in inflamed colonic epithelium and neutrophilic granulocytes. This study explores its properties as a biomarker in feces and plasma and, for the first time, compares fecal NGAL systematically with the existing fecal biomarker calprotectin. Methods Neutrophil gelatinase-associated lipocalin was measured in feces from 73 patients with IBD, 21 patients with infectious enterocolitis, 21 patients with irritable bowel syndrome, and 23 healthy subjects using ELISA. The results were correlated to calprotectin, clinical score, endoscopic score, and high-sensitive C-reactive protein. Plasma from 119 patients with IBD and 28 healthy controls was analyzed for NGAL. Results Fecal NGAL levels (median and interquartile range) were significantly elevated in active ulcerative colitis (UC) 6.05 (3.6–15.1) mg/kg and Crohn's disease (CD) 4.9 (1.5–7.7) mg/kg, compared with patients with inactive UC 1.3 (0.4–2.6) mg/kg, inactive CD 1.5 (0.5–1.7) mg/kg, irritable bowel syndrome 0.4 (0.2–0.6) mg/kg, and healthy controls (HC) 0.3 (0.1–0.4) mg/kg. Patients with infectious enterocolitis had significantly higher fecal-NGAL levels, 2.7 (1.4–5.6) mg/kg than HC. Sensitivity and specificity was 94.7% and 95.7%, respectively, for distinguishing between active IBD and HC. Stability of NGAL in stool was excellent for 7 days in room temperature. Plasma NGAL was significantly elevated in UC and CD compared with HC. Conclusions Fecal NGAL is a promising biomarker for IBD. As existing biomarkers are expressed mainly in granulocytes, NGAL's epithelial localization may give supplementary diagnostic information.

Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment

Abstract: Background and aim Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. Methods A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. Results In 2014, an estimated 230 470 individuals (range: 180 490-243 990) were living with HCV, among whom 75% were diagnosed (n = 172 720; range: 156 720-188 770), 20% had ever received treatment (n = 45 000; range: 39 280-50 720), and 11% had been cured (n = 24 750; range: 21 520-27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage ≥F3 doubled during the last decade, increasing from 9% (n = 18 580) in 2004 to 19% (n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. Conclusions The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals

Abstract: Background and Aim Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Methods Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. Results The overall SVR12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. Conclusions There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted.

Long-term outcome of surgical resection for intraductal papillary neoplasm of the bile duct.

Abstract: Background & Aims Intraductal papillary neoplasm of the bile duct (IPNB) is a specific type of bile duct tumor. Studies about the surgical outcomes for IPNB are few; therefore, we investigated the survival of patients who underwent curative surgical resection of IPNB. Methods We retrospectively reviewed the medical and pathological records of 148 IPNB patients who underwent curative-intent hepatic resection between January 2005 and December 2011, to examine the prognosis of IPNB. All demographic and operative parameters were analyzed the effect on survival of patients. Results: The median survival of IPNB patients was 1,326 days with a respective 1, 3, and 5 year overall survival of 83.6% (95%CI:76.5-88.7), 64.4% (95%CI:56.0-71.6), and 47% (95%CI:38.4-55.7). The level of invasiveness of IPNB predicted survival very well. For malignant IPNB, univariate analysis showed that serum CA19-9 level, lymph node metastasis, and completeness of resection were significant prognostic factors. Lymph node metastasis and completeness of resection were found in multivariate analysis to be significantly related to survival of the patients. Conclusions The level of invasiveness and lymph node status were found to be associated with patient survival, as was adequacy of surgery. We recommend R0 resection be attempted for patients with IPNB.

BISAP, RANSON, lactate and others biomarkers in prediction of severe acute pancreatitis in a European cohort.

Abstract: Background and Aim The study aims to assess and compare the predicting ability of some scores and biomarkers in acute pancreatitis. Methods We prospectively collected data from 269 patients diagnosed of acute pancreatitis, admitted to Virgen de las Nieves University Hospital between June 2010 and June 2012. Blood urea nitrogen (BUN), C-reactive protein, and creatinine were measured on admission and after 48 h, lactate and bedside index for severity acute pancreatitis (BISAP) only on admission and RANSON within the first 48 h. Definitions from 2012 Atlanta Classification were used. Area under the curve (AUC) was calculated for each scoring system for predicting severe acute pancreatitis (SAP), mortality, and intensive care unit (ICU) admission, obtaining optimal cut-off values from the receiver operating characteristic curves. Results Eight (3%) patients died, 17 (6.3%) were classified as SAP, and 10 (3.7%) were admitted in ICU. BISAP was the best predictor on admission for SAP, mortality, and ICU admission with an AUC of 0.9 (95% CI 0.83–0.97); 0.97 (95% CI 0.95–0.99); and 0.89 (95% CI 0.79–0.99), respectively. After 48 h, BUN 48 h was the best predictor of SAP (AUC = 0.96 CI: 0.92–0.99); BUN 48 h and BISAP were the best predictors for mortality (AUC = 0.97 CI: 0.95–0.99) and creatinine 48 h for ICU admission (AUC = 0.96 CI: 0.92–0.99). Lactate showed an AUC of 0.79 (CI: 0.71–0.88), 0.87 (CI: 0.78–0.96), and 0.77 (CI: 0.67–0.87) for SAP, mortality, and ICU admission, respectively. All parameters were predictors for SAP, mortality, and ICU admission, but C-reactive protein on admission was only a significant predictor of SAP. Conclusion Bedside index for severity acute pancreatitis is a good predictive system for SAP, mortality, and ICU admission, being useful for triaging patients for ICU management. Lactate could be useful for developing new scores.

Anatomical versus non‐anatomical resection for solitary hepatocellular carcinoma without macroscopic vascular invasion: A propensity score matching analysis

Abstract: Background and aim The superiority of anatomical resection (AR) in patients with hepatocellular carcinoma compared with non-anatomical resection (NAR) remains controversial. We aimed to investigate the prognostic outcomes of AR and NAR for solitary hepatocellular carcinoma (HCC) patients without macroscopic vascular invasion, using a propensity score matching (PSM) analysis. Methods A total of 305 consecutive HCC patients without macroscopic vascular invasion who underwent curative hepatectomy were included in our study. PSM was performed in order to eliminate possible selection bias. Results By PSM, the patients were divided into propensity-matched anatomical resection (PS-AR) (n = 114) and propensity-matched non-anatomical resection (PS-NAR) (n = 114) groups. The 1-year, 3-year, and 5-year overall survival rates were 90.4%, 77.7%, and 65.7% in PS-AR and 88.6%, 70.7%, and 52.2% in PS-NAR (P = 0.053), respectively. The 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 84.1%, 64.9%, and 45.1% in PS-AR and 75.4%, 48.1%, and 31.0% in PS-NAR (P = 0.005), respectively. Multivariate analysis showed that ICG-R15 (P = 0.022); the Barcelona clinic liver cancer staging (P = 0.044) and microvascular invasion (MVI; P = 0.005) were independent risk factors for the overall survival rate, while type of resection (P = 0.027), surgical margin (P = 0.039), and MVI (P = 0.024) were independent risk factors for the RFS rate. Patients who underwent NAR were prone to early recurrence and marginal recurrence. Subgroup analysis indicated that the RFS rate was significantly better in PS-AR than that in PS-NAR (surgical margin ≥ 1 cm) (P = 0.025). Better RFS rate was observed in PS-AR with MVI compared with PS-NAR (P = 0.016). Conclusions Anatomical resection contributed to improve the RFS rate in solitary HCC patients without macroscopic vascular invasion using PSM analysis, especially in patients with MVI.

Fecal biomarkers in inflammatory bowel disease.

Abstract: Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

Echoendoscopic ethanol ablation of tumor combined with celiac plexus neurolysis in patients with pancreatic adenocarcinoma.

Abstract: Background and aim Endoscopic ultrasonography guided-celiac plexus neurolysis relieves pain in patients with pancreatic cancer but with often suboptimal and transient results. The study aims to compare the efficacy and safety of endoscopic ultrasound-guided tumor ethanol ablation combined with celiac plexus neurolysis with respect to celiac plexus neurolysis alone for pain management in patients with pancreatic cancer. Methods Among 123 patients with unresectable pancreatic cancer referred to our Institution between 2006 and 2014, 58 treated with endoscopic ultrasound-guided celiac plexus neurolysis (Group 1) and 65 with the combined approach (Group 2) were compared. Logistic regression models were applied to identify predictors of pain relief. Results The two groups presented similar baseline clinical and tumoral parameters. Pre-procedural visual analog scale score was 7 in both groups (P = 0.8), and tumor max diameter was 38 mm (range 25-59) in Group 1 and 43 mm (22-59) in Group 2 (P = 0.4). The combined treatment increased pain relief and complete pain response rate (P = 0.005 and 0.003, respectively). Median duration of pain relief was 10 (7-14) and 18 (13-20) weeks in the two groups, respectively (P = 0.004). At multivariate regression, initial visual analog scale score and endoscopic technique adopted resulted significantly associated with pain relief. No severe treatment-related adverse events were reported. Median overall survival was 6.5 months (5.1-8.6) in Group 1 and 8.3 months (6-11.4) in Group 2 (P = 0.05). Conclusions Endoscopic ultrasound-guided tumor ablation combined with celiac plexus neurolysis appears to be superior to celiac plexus neurolysis alone in terms of pain control and overall survival.

Long non-coding ribonucleic acid zinc finger antisense 1 promotes the progression of colonic cancer by modulating ZEB1 expression

Abstract: Background and aim Long non-coding RNA ZFAS1 (zinc finger antisense 1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer. Methods Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time PCR analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT. Results ZFAS1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (p < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion and lymph node metastasis (p < 0.05). ZFAS1 and ZEB1 were also increased in patients’ plasma. Moreover, ZFAS1 promoted proliferation, invasion and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin. Conclusions LncRNAZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

Re-challenging FODMAPs: the low FODMAP diet phase two

Abstract: The low fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has good evidence for use in the treatment of patients with irritable bowel syndrome. Importantly, patients are encouraged not to remain on a strict low FODMAP diet long-term, and many patients maintain symptom improvement with a relaxed, moderate FODMAP restriction. The re-challenge phase is crucial to assist patients in identifying specific dietary triggers, reduce the level of dietary restriction required, and increase prebiotic intake. Limited evidence is available to guide best practice, but, in practice, beneficial outcomes can be seen through strategic food reintroductions. Here, we set out some practical recommendations based on clinical experience. Dietitians should tailor the challenge process to the individual patient and their needs. Food challenges should aim to improve dietary variety and nutritional adequacy while considering specific food preferences and usual dietary habits. Identifying FODMAP subgroups that are well tolerated is helpful, allowing the reintroduction of some moderate to high FODMAP foods back into the diet without symptom induction. FODMAP subtypes that are less well tolerated may also be reintroduced, but dosage and frequency of consumption need to be individualized. Additional challenges that face dietitians include consideration of patients with multiple dietary restrictions such as in vegetarians or patients with diabetes who are simultaneously following a low FODMAP diet. Ensuring nutritional adequacy is essential. The outcome of the re-challenge process aims to find a balance between good symptom control and expansion of the diet.

Nutritional, microbiological and psychosocial implications of the low FODMAP diet

Abstract: Dietary restriction of certain fermentable carbohydrates (low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet) is effective for managing symptoms of irritable bowel syndrome (IBS). However, there are potential consequences of this diet that relate to its impact on nutritional, microbiological, and health-related quality of life outcomes. Evidence suggests that the low FODMAP diet leads to some alterations in nutrient intake. For example, carbohydrate intake is reduced, and there is a decrease in the proportion of patients meeting the recommended intake for calcium. Intake of other macro and micro-nutrients appears to be adequate in the short term. As well as the impact on nutrient intake, extensive dietary modification can have a pronounced impact on the gastrointestinal microbiota. Indeed, recent data suggests the diet markedly reduces luminal Bifidobacteria concentration, and there is limited evidence that it reduces total bacteria abundance and concentration of other bacterial groups, for example, Faecalibacterium prausnitzii. Finally, despite the evidence for its clinical effectiveness in patients with IBS, the restrictive nature of the diet could pose a significant burden on patients, thereby limiting improvements, or indeed worsening health-related quality of life. In conclusion, while robust evidence supports the clinical effectiveness of the low FODMAP diet, it is important, considering the likelihood of its continued widespread use in IBS and other functional bowel disorders, that we extend our understanding of the impact of the diet on endpoints that may have potential consequences for long term health.

miR-200b-containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial-mesenchymal transition.

Abstract: Background and Aim Epithelial–mesenchymal transition (EMT), characterized by the decrease of E-cadherin (E-Cad) and increase in vimentin and alpha-smooth muscle actin (α-SMA), was demonstrated to participate in inflammatory bowel disease-related fibrosis. miR-200b plays an anti-fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR-200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR-200b in the treatment of fibrosis. Methods Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR-200b. The MVs packaged with miRNA-200b were harvested for the anti-fibrotic treatment using in vitro (transforming growth factor beta 1-mediated EMT in intestinal epithelial cells: IEC-6) and in vivo (TNBS-induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E-Cad, vimentin, α-SMA, ZEB1, and ZEB2, were detected. Results MiR-200b-MVs would significantly reverse the morphology in TGF-β1-treated IEC-6 cells and improve the TNBS-induced colon fibrosis histologically. The treatment of miR-200b-MVs increased miR-200b levels both in the IEC-6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E-Cad was increased, and the expressions of vimentin and α-SMA were decreased. ZBE1 and ZEB2, the targets of miR-200b, were also decreased. Conclusions miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2.