Showing papers in "Journal of Gastroenterology and Hepatology in 2020"

Covid-19 and the digestive system.

Abstract: The novel coronavirus disease is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Betacoronavirus genus that also includes the SARS-CoV and Middle East respiratory syndrome coronavirus. While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS-CoV-2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease.

The epidemiology of inflammatory bowel disease: East meets west

Abstract: The incidence of inflammatory bowel diseases (IBD) in East has risen over the past decade to become a global disease. The increasing number of studies on the incidence and course of IBD in East has enabled us to explore East versus West differences in the epidemiology of IBD which could enhance our understanding of the heterogeneity of the disease and eventually assist in the discovery of novel therapeutic targets and design of preventive strategies. Comparison of population-based data in East and West reveals that the incidence of IBD has risen rapidly in East while plateauing in West. Furthermore, the clinical presentation and course of IBD differs between East and West with more patients in East presenting with complicated disease. Considering the scarcity of population-based data from East and the lack of studies with long durations of follow-up, it remains to be clarified whether these differences reflect true differences in disease presentation. The effects of genetic and environmental risk factors contributing to IBD also differ between Eastern and Western populations. Considering the differential effects of genetic and environmental risk factors in East and West, future studies should seek to discover novel genetic and environmental risk factors which might specifically apply to eastern populations. In this narrative review, we compare the epidemiology of IBD between eastern and western countries by summarizing evidence from population-based cohort studies in the last ten years. Furthermore, we look at differences in genetic susceptibility and environmental triggers of IBD between East and West.

Overview of guidance for endoscopy during the coronavirus disease 2019 pandemic.

Abstract: From its beginning in December 2019, the coronavirus disease 2019 outbreak has spread globally from Wuhan and is now declared a pandemic by the World Health Organization. The sheer scale and severity of this pandemic is unprecedented in the modern era. Although primarily a respiratory tract infection transmitted by direct contact and droplets, during aerosol-generating procedures, there is a possibility of airborne transmission. In addition, emerging evidence suggests possible fecal-oral spread of the virus. Clinical departments that perform endoscopy are faced with daunting challenges during this pandemic. To date, multiple position statements and guidelines have been issued by various professional organizations to recommend practices in endoscopic procedures. This article aims to summarize and discuss available evidence for these practices, to provide guidance for endoscopy to enhance patient safety, avoid nosocomial outbreaks, protect healthcare personnel, and ensure rational use of personal protective equipment. Responses adapted to national recommendations and local infection control guidelines and tailored to the availability of medical resources are imminently needed to fight the coronavirus disease 2019 pandemic.

Gastric cancer prevention strategies: A global perspective

Abstract: Gastric cancer (GC) is the fifth most common cancer worldwide, and mortality rates are still high. Primary preventive strategies, aimed to reduce risk factors and promote protective ones, will lead to a decrease in GC incidence. Helicobacter pylori infection is a well-established carcinogen for GC, and its eradication is recommended as the best strategy for the primary prevention. However, the role of other factors such as lifestyle, diet, and drug use is still under debate in GC carcinogenesis. Unfortunately, most patients with GC are diagnosed at late stages when treatment is often ineffective. Neoplastic transformation of the gastric mucosa is a multistep process, and appropriate diagnosis and management of preneoplastic conditions can reduce GC-related mortality. Several screening strategies in relation to GC incidence have been proposed in order to detect neoplastic lesions at early stages. The efficacy of screening strategies in reducing GC mortality needs to be confirmed. This review provides an overview of current international guidelines and recent literature on primary and secondary prevention strategies for GC.

International consensus statements for endoscopic management of distal biliary stricture

Abstract: Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico-biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato-biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS.

Automatic detection of blood content in capsule endoscopy images based on a deep convolutional neural network.

Abstract: Background and aim Detecting blood content in the gastrointestinal tract is one of the crucial applications of capsule endoscopy (CE). The suspected blood indicator (SBI) is a conventional tool used to automatically tag images depicting possible bleeding in the reading system. We aim to develop a deep learning-based system to detect blood content in images and compare its performance with that of the SBI. Methods We trained a deep convolutional neural network (CNN) system, using 27 847 CE images (6503 images depicting blood content from 29 patients and 21 344 images of normal mucosa from 12 patients). We assessed its performance by calculating the area under the receiver operating characteristic curve (ROC-AUC) and its sensitivity, specificity, and accuracy, using an independent test set of 10 208 small-bowel images (208 images depicting blood content and 10 000 images of normal mucosa). The performance of the CNN was compared with that of the SBI, in individual image analysis, using the same test set. Results The AUC for the detection of blood content was 0.9998. The sensitivity, specificity, and accuracy of the CNN were 96.63%, 99.96%, and 99.89%, respectively, at a cut-off value of 0.5 for the probability score, which were significantly higher than those of the SBI (76.92%, 99.82%, and 99.35%, respectively). The trained CNN required 250 s to evaluate 10 208 test images. Conclusions We developed and tested the CNN-based detection system for blood content in CE images. This system has the potential to outperform the SBI system, and the patient-level analyses on larger studies are required.

Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Abstract: Background and aim Lean non-alcoholic fatty liver disease (NAFLD) is a potentially metabolically unhealthy state that refers to NAFLD occurring in non-overweight/nonobese subjects Yet its global epidemiology and metabolic characteristics are not extensively elucidated Methods PubMed, EMBASE, Web of Science and Cochrane databases were searched for eligible studies until January 2020 Random-effects/fixed-effects models were used to estimate the global prevalence of lean NAFLD and to compare clinical characteristics among lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD subjects "Lean" NAFLD was defined by ethnic-specific body mass index measurements in the normal range Meta-regression and subgroup analyses were performed to determine potential sources of heterogeneity Results A total of 33 observational studies were included with 205 307 individuals from 14 countries The global prevalence of lean NAFLD was 41% (95% confidence interval [CI]: 34-48%) In lean subjects, the prevalence of NAFLD was 97% (95% CI: 77-118%) The prevalence of lean NAFLD with diabetes, hypertension, metabolic syndrome, dyslipidemia, or central obesity was 06% (95% CI: 04-09%), 18% (95% CI: 12-25%), 14% (95% CI: 10-19%), 28% (95% CI: 19-37%), and 20% (95% CI: 16-24%), respectively The prevalence of lean NAFLD showed an upward trend between 1988 and 2017 Asian individuals had the highest prevalence of lean NAFLD (48%, 95% CI: 40-56%) Middle-aged people (45-59 years old) had the highest prevalence of lean NAFLD (44%, 95% CI: 32-55%) The prevalence of metabolic complications in lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD groups increased sequentially Conclusions Lean NAFLD occurs with metabolic complications and is not an uncommon condition The highest prevalence of lean NAFLD occurs in middle-aged individuals of Asian countries

The impact of deep convolutional neural network-based artificial intelligence on colonoscopy outcomes: A systematic review with meta-analysis.

Abstract: BACKGROUND AND AIM The utility of artificial intelligence (AI) in colonoscopy has gained popularity in current times. Recent trials have evaluated the efficacy of deep convolutional neural network (DCNN)-based AI system in colonoscopy for improving adenoma detection rate (ADR) and polyp detection rate (PDR). We performed a systematic review and meta-analysis of the available studies to assess the impact of DCNN-based AI-assisted colonoscopy in improving the ADR and PDR. METHODS We queried the following database for this study: PubMed, Embase, Cochrane Library, Web of Sciences, and Computers and Applied Sciences. We only included randomized controlled trials that compared AI colonoscopy to standard colonoscopy (SC). Our outcomes included ADR and PDR. Risk ratios (RR) with 95% confidence interval (CI) were calculated using random effects model and DerSimonian-Laird approach for each outcome. RESULTS A total of three studies with 2815 patients (1415 in SC group and 1400 in AI group) were included. AI colonoscopy resulted in significantly improved ADR (32.9% vs 20.8%, RR: 1.58, 95% CI 1.39-1.80, P = < 0.001) and PDR (43.0% vs 27.8%, RR: 1.55, 95% CI 1.39-1.72, P = < 0.001) compared with SC. CONCLUSION Given the results and limitations, the utility of AI colonoscopy holds promise and should be evaluated in more randomized controlled trials across different population, especially in patients solely undergoing colonoscopy for screening purpose as improved ADR will ultimately help in reducing incident colorectal cancer.

Non-alcoholic fatty liver disease and the incidence of myocardial infarction: A cohort study.

Abstract: BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease associated with an increased risk of cardiovascular disease (CVD), diabetes, and chronic kidney disease. Indeed, CVD is the most common cause of death in NAFLD patients. This study aimed to evaluate the association between NAFLD and the risk of incident myocardial infarction. METHODS This is a retrospective cohort study involving 111 492 adults over 40 years old without history of CVD, liver disease, or cancer at baseline who participated in a regular health screening exam between 2003 and 2013. Fatty liver was diagnosed by ultrasonography. RESULTS During 725 706.9 person-years of follow-up, 183 participants developed myocardial infarction (incidence rate 0.3 cases per 1000 person-years). The age, sex, and year of visit-adjusted hazard ratio (HR) for incident myocardial infarction comparing participants with NAFLD with those without it was 2.14 (95% confidence interval 1.59, 2.89). This association remained significant in fully adjusted models (HR 1.54; 95% confidence interval 1.11, 2.14). Compared with participants without NAFLD, in participants with low NAFLD fibrosis score (NFS) (< -1.455) and with intermediate-to-high NFS (≥ -1.455), the fully adjusted HRs for incident myocardial infarction were 1.70 (1.22, 2.36) and 1.88 (1.24, 2.87), respectively. CONCLUSION In this large cohort study, NAFLD was associated with an increased incidence of myocardial infarction independently of established risk factors. In addition, this association was similar in participants with and without evidence of more advanced NAFLD as indicated by the NFS. NAFLD patients may need to be carefully monitored and managed early to prevent myocardial infarction.

Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

Abstract: Background and aim Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. Methods A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. Results Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. Conclusions Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.

Abstract: Background and aim We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis. Methods We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases. Cirrhosis was defined by histological features, imaging data, and symptoms. We compared NAFLD-related HCC with or without cirrhosis and non-cirrhotic NAFLD with or without HCC. Results There were 48 non-cirrhotic HCC patients and 71 cirrhotic HCC patients. Multiple logistic regression analysis revealed that other than liver function factors, male gender (OR: 5.603, 95%CI: 1.577-19.900), light drinker (OR: 2.797, 95%CI: 1.031-7.589), and tumor size (OR: 1.031, 95%CI 1.009-1.055) differ significantly between these two groups. The recurrence rate was significantly lower in the non-cirrhotic HCC group than the cirrhotic HCC group, with risk factors being des-γ-carboxy prothrombin and the number of HCCs. The non-cirrhotic HCC group showed significantly better survival because of absence of non-cancerous liver failure. Comparison between non-cirrhotic NAFLD patients with or without HCC (n = 612) revealed the following risk factors for HCC: male gender (OR: 7.774, 95%CI: 2.176-27.775), light drinker (OR: 4.893, 95%CI: 1.923-12.449), and high FIB4 index (OR 2.634, 95%CI: 1.787-3.884). Conclusion In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB4 index. HCC recurrence and survival were only influenced by the tumor stage. We should be aware of alcohol consumption as a modifiable risk factor for HCC.

Consensus on eradication of Helicobacter pylori and prevention and control of gastric cancer in China (2019, Shanghai).

Abstract: Background and aim China is a country with high prevalence of Helicobacter pylori (H. pylori) infection, which in turn is closely related to the occurrence of gastric cancer. Therefore, the risks of H. pylori infection and gastric cancer are highly overlapping, and the prevention and treatment of H. pylori infection are necessary to prevent gastric cancer. Methods Based on evidence-based medicine and the Delphi method, the National Clinical Medical Research Center for Digestive Disease along with the National Early Gastrointestinal Cancer Prevention and Treatment Center Alliance organized dozens of experts in the fields of digestive diseases, H. pylori research, gastric cancer surgery, epidemiology, health economics, and health management to discuss the relationship between H. pylori eradication and prevention and the treatment of gastric cancer. Results A preliminary consensus on the relationship between H. pylori infection and gastric cancer, H. pylori eradication and gastric cancer prevention, and H. pylori screening and eradication strategy was reached. The consensus further clarified the relationship between H. pylori and gastric cancer and how to formulate future prevention and control strategies for gastric cancer. Conclusions This consensus could provide guidance on early detection, diagnosis, and treatment of H. pylori to reduce the occurrence of gastric cancer in China.

Regulation of lipid-induced macrophage polarization through modulating peroxisome proliferator-activated receptor-gamma activity affects hepatic lipid metabolism via a Toll-like receptor 4/NF-κB signaling pathway.

Abstract: Background and aim Chronic inflammation links closely to insulin resistance and lipid metabolism in nonalcoholic fatty liver disease (NAFLD). Macrophage M1 activation plays an important role in the initiation and continuing of pro-inflammatory response of NAFLD. Our study was to investigate whether macrophage M1/M2 polarization switching would affect hepatic inflammation and lipid metabolism through modulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activity in vivo and in vitro. Methods RAW264.7 macrophages were treated with different fatty acids, and cell culture supernatants were collected to prepare conditioned media (CM). Different co-culture systems between primary hepatocytes and CM from macrophages were established. A PPAR-γ agonist or antagonist was administered to regulate PPAR-γ activity and macrophage polarization. M1/M2 phenotype markers, inflammatory signaling pathway, and lipid-related genes expression were determined. Wild-type C57BL/6 mice were fed a high-fat diet to induce NAFLD and given rosiglitazone to regulate PPAR-γ activity in vivo. Results Saturated fatty acids induced M1-polarized macrophages while polyunsaturated fatty acids induced M2-polarized macrophages. M1-polarized macrophages significantly promoted lipid synthesis and accumulation in primary hepatocytes through upregulation of a toll-like receptor 4 (TLR4)/NF-κB signaling pathway. The PPAR-γ agonist made lipid-induced M1-polarized macrophages switch to an M2-predominant phenotype, while PPAR-γ antagonist had the opposite effect. Macrophage polarization shifting subsequently affected lipid metabolism in primary hepatocytes. Administration of rosiglitazone improved high-fat diet induced hepatic steatosis and lipid metabolism through reducing hepatic TLR4/NF-κB expression and M1-polarized Kupffer cells. Conclusions Lipid-induced macrophage M1 polarization promoted hepatic lipid metabolism. Modulation of PPAR-γ activity could shift macrophage polarization and subsequently affect lipid metabolism. Upregulation of the TLR4/NF-κB signaling pathway is closely linked to dysregulated lipid metabolism in NAFLD.

Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non-alcoholic fatty liver disease.

Abstract: Background and aim A causal relationship between changes of the gut microbiome and non-alcoholic fatty liver disease (NAFLD) remains unclear. We demonstrated that endogenous ethanol (EnEth) produced by intestinal microbiota is likely a causative agent of NAFLD. Methods Two mutants with different alcohol-producing abilities, namely, W14-adh and W14Δadh, were constructed using the clinical high alcohol-producing (HiAlc) Klebsiella pneumoniae strain W14 as a parent. Damage to hepatocytes caused by bacteria with different alcohol-producing capacities was evaluated (EtOH group as positive control). The ultrastructural changes of mitochondria were assessed via transmission electron microscopy (TEM). Hepatic levels of mitochondrial reactive oxygen species (ROS), DNA damage, and adenosine triphosphate were examined. Results The results illustrated that steatosis was most severe in the W14-adh group, followed by the W14 group, whereas the W14Δadh group had few fatty droplets. TEM and examination of related protein expression revealed that the mitochondrial integrity of HepG2 hepatocytes was considerably damaged in the EtOH and bacteria treatment groups. The impaired mitochondrial function in HepG2 hepatocytes was evidenced by reduced adenosine triphosphate content and increased mitochondrial ROS accumulation and DNA damage in the EtOH and bacteria treatment groups, especially the W14-adh group. Meanwhile, liver injury and mitochondrial damage were observed in the hepatocytes of mice. The livers of mice in the W14-adh group, which had the highest ethanol production, exhibited the most serious damage, similar to that in the EtOH group. Conclusions EnEth produced by HiAlc bacteria induces mitochondrial dysfunction in NAFLD.

Prevalence of the pathobiont adherent-invasive Escherichia coli and inflammatory bowel disease: a systematic review and meta-analysis.

Abstract: BACKGROUND AND AIM Escherichia coli pathobionts and particularly the adherent-invasive E. coli (AIEC) may play a putative role in initiating and maintaining the inflammatory process in the intestinal tissues of inflammatory bowel disease (IBD) patients, by providing stimulatory factors that trigger gut immune system activation. The aim of this study is to conduct a systematic review and meta-analysis to determine the prevalence of AIEC among patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS Electronic databases were searched up to February 2020 for relevant publications reporting the prevalence of AIEC in IBD patients. The prevalence rate of AIEC among CD and UC patients, the odds ratio (OR) and 95% confidence interval (CI) were calculated compared to non-IBD controls. RESULTS The final dataset included 12 studies, all investigating AIEC isolates from ileal/colonic specimens. The OR for prevalence of AIEC in CD patients was 3.27 (95% CI 1.79-5.9) compared with non-IBD controls. The overall pooled prevalence of AIEC among CD patients was 29% (95% CI 0.17-0.45), whereas this prevalence was calculated to be 9% (95% CI 0.03-0.19) in controls. Moreover, the prevalence of AIEC in UC subjects was calculated 12% (95% CI 0.01-0.34), while AIEC showed a prevalence of 5% (95% CI 0.0-0.17) among the controls. The OR for prevalence of AIEC in UC patients was 2.82 (95% CI 1.11-7.14) compared with controls. CONCLUSIONS There is a substantial increase in the prevalence of AIEC in IBD patients compared with controls. This review supports the growing evidence that AIEC could be involved in both CD and UC pathogenesis.

Is fecal calprotectin an accurate marker in the management of Crohn's disease?

Abstract: Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.

COVID-19 and its effects on the digestive system and endoscopy practice

Abstract: The Coronavirus Disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been classified as a pandemic by the World Health Organization in March 2020. Several studies have demonstrated that the gastrointestinal (GI) tract is also a potential route. As the pandemic is continuously evolving, and more data are made available, this article highlights the best evidence and practices regarding the effects of the SARS-CoV-2 virus relevant to GI practice. Published clinical studies have supported that SARS-CoV-2 affects the GI tract and the liver. The largest published dataset comprised of 4243 patients and showed a pooled prevalence of GI symptoms at 17.6%. GI symptoms varied and usually preceded pulmonary symptoms by 1–2 days. These include anorexia (26.8%), nausea and vomiting (10.2%), diarrhea (12.5%), and abdominal pain (9.2%). Incidence of liver injury ranges from 15 to 53%. Evidence shows that the severity of COVID-19 infection is compounded by its effects on nutrition, most especially for the critically ill. As such, nutrition societies have recommended optimization of oral diets and oral nutritional supplements followed by early enteral nutrition if nutritional targets are not met, and parenteral nutrition in the distal end of the spectrum. In addition to possible fecal–oral transmission, GI endoscopy procedures, which are considered to be aerosol-generating procedures, contribute to increased risk to GI health-care professionals. Infection prevention measures and guidelines are essential in protecting both patients and personnel.

A meta‐analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome

Abstract: Background Enteric microbiota is increasingly being recognized as an important factor in the pathogenesis of irritable bowel syndrome (IBS). The reported prevalence of small intestinal bacterial overgrowth (SIBO) in subjects with IBS is highly variable, and there is no consensus on the role of SIBO in different subtypes of IBS, and indications and methods of testing. Methods A comprehensive literature search was performed for studies applying tests for SIBO in subjects with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of SIBO in subjects with IBS using different tests. The odds ratios of SIBO among subjects with IBS as compared with healthy controls using different tests were calculated. Results Of the available studies (22, 17, 5, and 3 using lactulose and glucose hydrogen breath tests [LHBT and GHBT], jejunal aspirate culture, and more than one tests, respectively) meeting the inclusion criteria, 36.7% (95% confidence interval [CI] 24.2-44.6) had a positive test for SIBO. Patients with IBS were 2.6 (95% CI 1.3-6.9) and 8.3 (95% CI 3.0-5.9) times more likely to have a positive test for SIBO as compared with healthy controls using GHBT and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS were more likely to have positive GHBT as compared with the other subtypes. Conclusions Patients with IBS were more likely to have SIBO as compared with healthy subjects using GHBT and jejunal aspirate culture but not using LHBT. Patients with diarrhea-predominant IBS more often have SIBO.

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting.

Abstract: Background and aim Lenvatinib has been recently approved as a first-line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child-Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real-world setting. Methods Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.

Does cold snare polypectomy completely resect the mucosal layer? A prospective single‐center observational trial

Abstract: BACKGROUND AND AIM The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy (CSP) is unknown. We examined the incidence of incomplete muscularis mucosa resection both with and without cold snare defect protrusion (CSDP). METHODS We prospectively enrolled patients undergoing polypectomy for 4 to 9mm nonpedunculated polyps. We evaluated the presence of CSDP immediately following CSP and biopsied the CSDP or the center of the mucosal defect without CSDP. The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically. The primary outcome was the incidence of incomplete mucosal layer resection defined as the presence of muscularis mucosa or residual polyp in the biopsies. RESULTS From August 2017 to October 2018, 188 patients were screened, and 357 polyps were included. CSDP was detected in 122/355 (34%) evaluated mucosal defects. Excluding five lesions requiring hemostasis immediately following CSP, 352 mucosal defects were biopsied. After excluding 102 biopsies containing normal mucosa, we evaluated 250 biopsies. The overall incidence of incomplete mucosal layer resection was 63% (159/250), 76% (68/90) with CSDP and 57% (91/159) without CSDP (P < 0.01). Both univariate and multivariate analyses showed that size (≥ 6 mm), resection time (≥ 5 s), and serrated lesions were risk factors for CSDP. CONCLUSIONS Cold snare defect protrusion (CSDP), which was present with 36%, was a good indicator for incomplete mucosal layer resection. Even in nonCSDP polypectomies, 57% of the mucosal layer was not removed completely. Thus, CSP should be used for intra-epithelial lesions only, and careful pretreatment evaluation is recommended.

Herbal medicine in the treatment of functional gastrointestinal disorders: A systematic review with meta-analysis.

Abstract: Background and aims The efficacy of herbal medicines (HMs) for functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional dyspepsia (FD) and functional constipation (FC) is controversial. A systematic review with meta-analysis was conducted to determine their effectiveness for FGIDs. Methods We searched the following electronic databases till July 2019 with English language restriction: The Cochrane Library, EMBASE and PUBMED. Randomized double-blind controlled trials of HMs compared with placebo or conventional pharmacological drugs for adult FGIDs patients were included. Results In total, 49 trials involving 7396 participants with FGIDs were included. The risk of bias was low in 9, unclear in 36, and high in 4 trials. More than 33 different herbal formulae were tested. HMs demonstrated statistically significant benefits for symptom improvement compared with placebo in 46 trials (RR = 1.67, 95% CI 1.48-1.88). When compared with conventional pharmacological therapy in 5 trials, HMs were found to be non-inferior (RR = 1.10, 95% CI 1.03-1.18). The number of trials with regards to FD, IBS and FC were 19, 23 and 7 respectively. Subgroup analysis found that HMs were better than placebo in alleviating symptoms for FD (RR = 1.50, 95% CI 1.32-1.69), IBS (RR = 1.62, 95% CI 1.32-1.97) and FC (RR = 3.83, 95% CI 2.26-6.50). HMs tended to have more patients with adverse events than placebo, but similar to conventional pharmacological drugs. Conclusions Our findings provide a positive signal for HMs as a potentially well-tolerated and effective treatment for FGIDs, deserving further examination in high-quality trials.

Nationwide validation study of diagnostic algorithms for inflammatory bowel disease in Korean National Health Insurance Service database

Abstract: Background and aim We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. Method Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population. Results A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value Conclusions We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database.

Effect of weight loss induced by laparoscopic sleeve gastrectomy on liver histology and serum adipokine levels.

Abstract: BACKGROUND & AIM Bariatric surgery is a valid treatment option for persons with non-alcoholic fatty liver disease. This study prospectively examined the impact of laparoscopic sleeve gastrectomy (LSG) on liver histopathology, and blood levels of adiponectin, leptin, resistin, and pre-B cell enhancing factor/Nampt/visfatin. PATIENTS & METHODS In 81 patients with non-alcoholic fatty liver disease who underwent LSG, paired liver biopsies and blood specimens were obtained before and 18 months after LSG. Differences between preoperative and 18 months postoperative data were tested by paired Student's t-test or Wilcoxon rank test as appropriate. RESULTS At follow up, there was a significant improvement in biochemical markers for glucose homeostasis, including fasting glucose, HbA1c, insulin levels, and homeostatic model assessment index. Postoperative liver function tests, namely serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase level, showed a significant improvement compared to before weight loss. The number of patients who had definite, borderline, or no non-alcoholic steatohepatitis was 43 (53%), 27 (33%), and 11 (14%), respectively, at baseline, and 9 (11%), 32 (40%), and 40 (49%) at 18-month post-surgery follow up. A significant reduction in steatosis, liver fibrosis, lobular inflammation, and hepatocyte ballooning was observed in the postoperative biopsies (P < 0.001 each). In addition, at the follow-up assessment, there was a significant increase in serum adiponectin levels and significant decline in serum levels of leptin, resisitin, and pre-B cell enhancing factor/Nampt/visfatin. CONCLUSION Weight loss after sleeve gastrectomy was associated with a significant improvement in several metabolic parameters, liver enzyme levels, liver histopathology, and changes in serum adipokine levels towards antidiabetic and anti-inflammatory profiles.

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon

Abstract: BACKGROUND AND AIM Microbiota have been associated with several diseases including colorectal cancer (CRC). This study aimed to evaluate the microbiota in early/invasive CRC utilizing stool and cytological brushes to determine differences in relative abundance (RA). METHODS Colonoscopy patients referred for endoscopic submucosal dissection or previous to CRC surgery were prospectively enrolled. Stool was collected pre-bowel preparation; and brush samples were taken during colonoscopy (three regions). DNA extraction, 16S rRNA next generation sequencing, and biostatistics (qiime and stamp software packages) followed. Primary outcome was the difference in RA of the Fusobacterium genus between the groups. Secondary outcomes included analyses of other microbiota. RESULTS Twenty-five patients were included, of which 14 had invasive cancer (≥ 1000 mm into the submucosa). The three major genera for invasive cancer were Bacterioides, Oribacterium, and Fusobacterium, whereas for early cancer were Oribacterium, Bacterioides, and Prevotella (decreasing order of RA). There was a significantly higher RA of Fusobacterium in the invasive cancer group (9.65% vs 0.95%, respectively, P < 0.001). The RA of all genera was similar throughout the colon. In addition to Fusobacterium, the genera Corynebacterium, Enterococcus, Neisseria, Porphyromonas, and Sclegelella showed statistically higher RA in the invasive cancer group. Conversely, the genera Oribacterium, Desulfovibrio, Clostridiales, and Lactobacillus showed lower RA in the invasive cancer group. CONCLUSIONS The RA of Fusobacterium is higher with invasive CRC than in early CRC patients. In addition, five other bacteria genera were found to be increased, and four decreased in invasive CRC patients. The microbiota per patient was similar throughout the colon.

DRP1 upregulation promotes pancreatic cancer growth and metastasis through increased aerobic glycolysis

Abstract: Background Mitochondrial shape is dynamically changed by fusion and fission processes in cells, and dysfunction of this process has become one of the emerging hallmarks of cancer. However, the expression patterns and biological effects of mitochondrial fission and fusion proteins in pancreatic cancer (PC) are still unclear. Methods The expressions of mitochondrial fission and fusion proteins were first evaluated by quantitative reverse transcription polymerase chain reaction and western blot analysis in both PC cell lines and tissue samples. In addition, the biologic functions of the differentially expressed proteins in PC cell growth and metastasis both in vitro and in vivo and their potential underlying mechanisms were systematically explored. Results We first found that DRP1 was substantially upregulated in PC cell lines and tissue samples mainly due to the downregulation of miR-29a, which contributed to the poor survival of PC patients. DRP1 promoted the growth and metastasis of PC cells both in vitro and in vivo by inducing G1-S cell cycle transition and matrix metalloproteinase 2 secretion. Mechanistic investigations revealed that increased DRP1 upregulation-mediated mitochondrial fission and subsequently enhanced aerobic glycolysis were involved in the promotion of growth and metastasis by DRP1 in PC cells. Conclusions Our findings demonstrate that mitochondrial fusion protein DRP1 plays a critical oncogenic role in PC cells by enhancing aerobic glycolysis, which could serve as a novel therapeutic target for PC treatment.

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.

Abstract: BACKGROUND AND AIM The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). METHODS The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. RESULTS A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjogren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. CONCLUSIONS Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

Effect and mechanism of vitamin D on the development of colorectal cancer based on intestinal flora disorder

Abstract: BACKGROUND To investigate the correlation between the level of circulating vitamin D and the development of colorectal cancer (CRC) and to clarify the effect and mechanism of vitamin D on the development of CRC. METHODS Serum samples from 63 patients with CRC (CRC group) and 61 healthy volunteers (normal group) were collected. Azoxymethane + dextran sodium sulfate-induced CRC mouse model and dietary models with different doses of vitamin D were established to verify whether vitamin D supplementation could reverse the occurrence and development of CRC at the overall animal level. Intestinal barrier integrity and microbial defense response were evaluated by detection of intestinal flora and expression of related genes. RESULTS In the clinical serum samples, compared with the normal group, the level of 25 (OH) D3 in the CRC group was relatively low (P < 0.01), which was consistent with the clinical situation in mice. Vitamin D deficiency aggravated the deterioration of enteritis and intestinal cancer in CRC mice, whereas the overall condition of CRC mice improved after vitamin D supplementation. Vitamin D has a significant regulatory effect on the homeostasis of the intestinal flora, particularly in the regulation of intestinal probiotics, Akkermansia muciniphila-mediated colon barrier integrity. CONCLUSIONS Vitamin D deficiency is closely related to the high incidence of CRC, and vitamin D supplementation can inhibit the occurrence and development of CRC. Vitamin D plays a role in the reversal of CRC mainly through the regulation of intestinal flora, especially the regulation of A. muciniphila-mediated colon barrier integrity.

Comparing point shear wave elastography (ElastPQ) and transient elastography for diagnosis of fibrosis stage in non-alcoholic fatty liver disease.

Abstract: Background and Aim: Medication non-adherence is common among patients with inflammatory bowel disease (IBD) and has been associated with worse outcomes As studies examining the frequency and severity of coronavirus disease 2019 (COVID-19) infection in immunosuppressed populations are currently lacking, both medical and consumer communities have varying views on the role of immunosuppression during this pandemic We aimed to examine medication adherence and complementary and alternative medication (CAM) usage during the COVID-19 pandemic among patients with IBD Methods: We undertook an internet-based questionnaire of patients with IBD from two South Australian tertiary IBD units Demographics, disease activity by Harvey-Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI), IBD medication use, medication non-adherence attributed to COVID-19, and CAM usage frequency were determined Validated scores of medication adherence and beliefs about medicines, including concern score, necessity score, harm score, and overuse score, were obtained Results: Of 262 respondents (median age, 46 years;55% female;response rate, 30 4%), some 7% reported self-initiated missed doses or dose reduction of IBD medications directly attributable to the COVID-19 pandemic Stopped medications included immunomodulators and steroids, and medications deliberately omitted or dose-reduced included immunomodulators and biological agents Positive associations with medication non-adherence included low validated medication adherence score (P<0 001), higher concern over medicines score (P = 0 007), current corticosteroid requirement (P = 0 036), and active disease (P = 0 04), but not medication necessity score (P = 0 59) Regular CAM usage was present in 26% and was frequently aimed at treating mental health (92%) and IBD (66%), but not COVID-19 (3%) Frequent use of CAM was associated with higher disease activity score (P = 0 036), low medication adherence score (P = 0 003), higher harm of medicines score (P = 0 02), and concern over medicines score (P = 0 02), but not necessity of medicines score (P = 0 6) Rates of COVID-19 in South Australia at the time of the survey were low, ranging from 0 to 11 new cases per day, with minimal or no community transmission Conclusion: Even in the setting of low COVID-19 prevalence, the pandemic influenced IBD medication adherence negatively in 1 in 14 patients Importantly, this non-adherence was associated with deleterious outcomes, such as increased disease activity and corticosteroid use Individuals using CAM cited more concerns and more perceived harm from conventional medication and were more likely to report medication non-adherence Understanding underlying beliefs driving IBD medication non-adherence is crucial to identifying patients at risk of adverse IBD outcomes

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

Abstract: Background and aim Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant. Methods A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed. Results Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events. Conclusion Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

Significant decrease in the prevalence of hepatitis C infection after the introduction of direct acting antivirals.

Abstract: Background and aim Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. Methods This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. Results A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. Conclusions The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.