Showing papers in "Journal of Gastroenterology and Hepatology in 2018"

Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment.

Abstract: Asia–Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017—Part 1: Definition, risk factors and assessment Vincent Wai-Sun Wong,* Wah-Kheong Chan, Shiv Chitturi, Yogesh Chawla, Yock Young Dan,** Ajay Duseja, Jiangao Fan, Khean-Lee Goh, Masahide Hamaguchi, Etsuko Hashimoto, Seung Up Kim, Laurentius Adrianto Lesmana,*** Yu-Cheng Lin, Chun-Jen Liu, Yen-Hsuan Ni, Jose Sollano, Simon Kin-Hung Wong, Grace Lai-Hung Wong,* Henry Lik-Yuen Chan* and Geoff Farrell *Department ofMedicine and Therapeutics, State Key Laboratory of Digestive Disease andDepartment of Surgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia; Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; **Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Diabetology, Kameoka Municipal Hospital, Kameoka and Departments of InternalMedicine andGastroenterology, TokyoWomen’sMedical University, Tokyo, Japan; Department of InternalMedicine, Institute of Gastroenterology, Yonsei University College ofMedicine, Seoul, Korea; ***Digestive Disease andGI Oncology Centre,Medistra Hospital, Jakarta, Indonesia; Hepatitis Research Center, National Taiwan University, and Department of Internal Medicine, Hepatitis Research Center and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan; and University of Santo Tomas, Manila, The Philippines

Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation

Abstract: Background and aim Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS. Methods Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology. Results Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS. Conclusion Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.

Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma

Abstract: Partial hepatectomy and liver transplantation are potentially curative treatments in selected patients with hepatocellular carcinoma (HCC). Unfortunately, a high postoperative tumor recurrence rate significantly decreases long-term survival outcomes. Among multiple prognostic factors, the presence of microvascular invasion (MVI) has increasingly been recognized to reflect enhanced abilities of local invasion and distant metastasis of HCC. Unfortunately, MVI can only currently be identified through histopathological studies on resected surgical specimens. Accurate preoperative tests to predict the presence of MVI are urgently needed. This paper reviews the current studies on incidence, pathological diagnosis, and classification of MVI; possible mechanisms of MVI formation; and preoperative prediction of the presence of MVI. Furthermore, focusing on how the postoperative management can be improved on histopathologically confirmed patients with HCC with MVI, and the potential roles of using predictive tests to estimate the risk of presence of MVI, helps in preoperative therapeutic decision-making in patients with HCC.

The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 2: Management and special groups.

Abstract: Yock Young Dan served as an advisory board member and has received research grants from AbbVie, Bristol-Myers Squibb, and Gilead Sciences. : This project was supported by a grant from the Journal of Gastroenterology and Hepatology Foundation.

Helicobacter pylori management in ASEAN: The Bangkok consensus report

Abstract: Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.

Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease.

Abstract: Background and aim We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD). Methods We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated. Results The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19-2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively). Conclusions PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis.

Insights into Roseburia intestinalis which alleviates experimental colitis pathology by inducing anti-inflammatory responses

Abstract: BACKGROUND AND AIM The study aims to elucidate the anti-inflammatory effect and mechanism of Roseburia intestinalis (R. intestinalis) in Crohn's disease (CD). METHODS 16S-rRNA genome sequencing technique is used to detect the characteristics of intestinal microbiota in untreated CD patients and healthy controls. Then the study investigates the effects of R. intestinalis on disease activity index score, intestinal pathology, the differentiation of Treg cells, and the expressions of Thymic stromal lymphopoietin (TSLP), TGF-β and IL-10 by using TNBS colitis models. At the cellular level, the study uses LPS to stimulate Caco-2 cells to conduct inflammation models and then co-culture with R. intestinalis and detect changes of TSLP and TGF-β. The study then uses R. intestinalis to stimulate peripheral blood mononuclear cells, and the change of Treg cells was detected. RESULTS Genome sequencing of fecal samples from untreated CD patients (n = 10) revealed decreases in the abundance and diversity of intestinal microbiota, including R. intestinalis. Moreover, R. intestinalis reduced disease activity index scores, colon shortening, intestinal mucosal epithelial injury, and mucosal lymphocyte infiltration in a colitis mice model. It suppressed intestinal inflammation by increasing Treg cell numbers and expression of the anti-inflammatory cytokines TSLP, TGF-β, and interleukin-10 (P < 0.05). R. intestinalis also increased secretion of TSLP and TGF-β in lipopolysaccharide-treated Caco-2 cells. CONCLUSION These findings suggest that R. intestinalis suppresses CD pathogenesis by inducing anti-inflammatory responses.

Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis

Abstract: Background and aim The gut microbiota is suggested to play an important role in the pathogenesis of ulcerative colitis (UC). However, interindividual and spatial variations hamper the identification of UC-related changes. We thus investigated paired mucosa-associated microbiota obtained from both inflamed and non-inflamed sites of UC patients and corresponding sites of non-inflammatory bowel disease (IBD) controls. Methods Mucosal biopsies of both inflamed and non-inflamed sites were obtained from 14 patients with active UC of the left-sided or proctitis type. Paired mucosal biopsies of the corresponding sites were obtained from 14 non-IBD controls. The microbial community structure was investigated using 16S ribosomal RNA gene sequences, followed by data analysis using qiime and LEfSe softwares. Results Microbial alpha diversity in both inflamed and non-inflamed sites was significantly lower in UC patients compared with non-IBD controls. There were more microbes of the genus Cloacibacterium and the Tissierellaceae family, and there were less microbes of the genus Neisseria at the inflamed site when compared with the non-inflamed site in UC patients. Decreased abundance of the genera Prevotella, Eubacterium, Neisseria, Leptotrichia, Bilophila, Desulfovibrio, and Butyricimonas was evident at the inflamed site of UC patients compared with the corresponding site of non-IBD controls. Among these taxa, the genera Prevotella and Butyricimonas were also less abundant at the non-inflamed site of UC patients compared with the corresponding site in non-IBD controls. Conclusions Mucosal microbial dysbiosis occurs at both inflamed and non-inflamed sites in UC patients. The taxa showing altered abundance in UC patients might mediate colonic inflammation.

Crohn's disease associated strictures.

Abstract: Crohn's disease (CD) is a chronic relapsing and remitting disease that can affect any segments of the gastrointestinal tract. More than 50% of patients with CD develop stricturing or penetrating complications within the first 10 years after diagnosis. Strictures can lead to intestinal obstruction, which is a common indication for surgery. Despite significant advances in the understanding of the pathogenesis of intestinal fibrostenosis, imaging and therapeutic armamentarium of CD, the risk of intestinal surgery remained significantly high. Endoscopic balloon dilation is a promising first-line alternative to surgery as it is less invasive and could preserve intestinal length. In this review, we will evaluate the literature on the mechanism of intestinal fibrosis, emerging imaging techniques, and management strategies for CD associated strictures.

Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes.

Abstract: Background and Aim Little is known about the diagnostic value of hepatic steatosis index (HSI) and fatty liver index (FLI), as well as their link to metabolic syndrome in type 1 diabetes mellitus. We have screened the effectiveness of FLI and HSI in an observational pilot study of 40 patients with type 1 diabetes. Methods FLI and HSI were calculated for 201 patients with type 1 diabetes. Forty patients with FLI/HSI values corresponding to different risk of liver steatosis were invited for liver magnetic resonance study. In-phase/opposed-phase technique of magnetic resonance was used. Accuracy of indices was assessed from the area under the receiver operating characteristic curve. Results Twelve (30.0%) patients had liver steatosis. For FLI, sensitivity was 90%; specificity, 74%; positive likelihood ratio, 3.46; negative likelihood ratio, 0.14; positive predictive value, 0.64; and negative predictive value, 0.93. For HSI, sensitivity was 86%; specificity, 66%; positive likelihood ratio, 1.95; negative likelihood ratio, 0.21; positive predictive value, 0.50; and negative predictive value, 0.92. Area under the receiver operating characteristic curve for FLI was 0.86 (95% confidence interval [0.72; 0.99]); for HSI 0.75 [0.58; 0.91]. Liver fat correlated with liver enzymes, waist circumference, triglycerides, and C-reactive protein. FLI correlated with C-reactive protein, liver enzymes, and blood pressure. HSI correlated with waist circumference and C-reactive protein. FLI ≥ 60 and HSI ≥ 36 were significantly associated with metabolic syndrome and nephropathy. Conclusions The tested indices, especially FLI, can serve as surrogate markers for liver fat content and metabolic syndrome in type 1 diabetes.

Irritable bowel syndrome in Asia: pathogenesis, natural history, epidemiology and management

Abstract: Historically, the epidemiology of gastrointestinal diseases in Asia was different from that in Western countries. Early studies suggested a low prevalence of irritable bowel syndrome (IBS) in Asia. As the diagnosis of IBS is symptom-based and as symptom perception, expression, and interpretation are influenced by sociocultural perspectives including language, the presentation of IBS is expected to vary in different communities. Furthermore, the pathogenesis is multifactorial with psychosocial (stress, illness, behavior, and diet) and biological (infection, gut microbiota, and immune activation) variables interacting, and so, the present study can anticipate that the development of IBS will vary in different environments. In recognition of this aspect of functional gastrointestinal disorders, the recently published Rome IV documents have provided greater focus on cross-cultural factors. In this review, the present study seeks to highlight Asian perspectives by identifying historical trends and recent publications from the region and comparing these with the observations from Western societies.

Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients.

Abstract: BACKGROUND AND AIM Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control. METHODS Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3 months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B. RESULTS At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90 ± 4.62 and 4.64 ± 5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42 ± 1.85 was showed (P < 0.001); in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose, and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of sustained virologic response patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strictly associated with HCV clearance; however, patients with the highest levels of fibrosis remain associated with some degree of IR. CONCLUSIONS The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.

Low fermentable oligo‐di‐mono‐saccharides and polyols diet versus general dietary advice in patients with diarrhea‐predominant irritable bowel syndrome: A randomized controlled trial

Abstract: BACKGROUND AND AIM Recent evidence indicates that new approach of the diet with low fermentable oligo-di-mono-saccharides and polyols (FODMAPs) may have an effective role in management of the patients with irritable bowel syndrome (IBS). We compared the results of low FODMAP diet with current dietary treatment, general dietary advices (GDA), on the clinical response in patients with diarrhea subtype of IBS (IBS-D). METHODS In this randomized, controlled, single-blind trial, we included 110 patients with IBS-D in two intervention groups. Participants were randomly assigned to the low FODMAP diet (n = 55) and GDA (n = 55) for 6 weeks after a 10-day screening period. Gastrointestinal symptoms and bowel habit status were evaluated using a symptom severity scoring system and Bristol stool form scale pre-intervention and post-intervention. Patients completed 3-day food diary before and after the intervention. RESULTS Of 110 patients, 101 completed the dietary interventions. At the baseline, the nutrient intake, severity of symptoms, and demographic data were similar between two groups. After 6 weeks, the low FODMAP diet improves significantly overall gastrointestinal symptoms scores, stool frequency, and consistency versus GDA group (P < 0.001, P < 0.001, and P = 0.003, respectively). Compared with the baseline, both intervention groups expressed a significant reduction in overall scores of symptom severity scoring system, abdominal pain, distension, consistency, and frequency, but this reduction is greater in low FODMAP diet group. CONCLUSIONS Both low FODMAP diet and GDA in patients with IBS-D led to adequate improvement of gastrointestinal symptoms for 6 weeks. However, the low FODMAP diet has greater benefits in IBS improvement.

Screening for non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus using transient elastography.

Abstract: BACKGROUND AND AIM The recommendation in regard to screening for non-alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients. METHODS This is a cross-sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy. RESULTS The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749-8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056-2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025-1.070, P < 0.001) while advanced fibrosis was associated with serum high-density lipoprotein cholesterol (OR 0.355, 95% CI 0.126-0.997, P = 0.049), alanine aminotransferase (OR 1.023, 95% CI 1.009-1.037, P = 0.001), γ-glutamyltransferase (OR 1.005, 95% CI 1.001-1.008, P = 0.017), and platelet levels (OR 0.995, 95% CI 0.992-0.999, P = 0.010). Seventy-one patients underwent liver biopsy. The majority had non-alcoholic steatohepatitis (83.1%) and ≥ F1 fibrosis (87.3%) while advanced fibrosis was seen in 36.6%. CONCLUSION The prevalence of NAFLD and advanced fibrosis based on transient elastography is high among T2DM patients.

Effect of the gluten-free diet on cardiovascular risk factors in patients with coeliac disease: A systematic review.

Abstract: Introduction A gluten free diet (GFD), the mainstay of treatment for celiac disease, is being increasingly adopted by people without this condition. The long-term health effects of this diet, apart from its beneficial effect on enteropathy in celiac disease, are unclear. Concerns exist that the GFD may result in micronutrient deficiencies, increased exposure to toxins such as arsenic, and an increased cardiovascular risk. This systematic review addresses the effect of the GFD on several modifiable cardiovascular risk factors. Methods and Results A systematic search of the literature addressing the GFD and blood pressure, glycaemia, body mass index, waist circumference, and serum lipids in patients before and after adoption of a GFD was conducted using the MEDLINE, EMBASE, PSYCInfo and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Two authors performed abstract and full text screening, and quality assessment: 5372 articles were identified, from which 27 were included. Lack of control groups in all but one study prevented meta-analysis of results. Overall study quality was low, and restricted to patients with celiac disease. Consistent findings across studies included an increase in total cholesterol, high density lipoprotein, fasting glycaemia and body mass index (whilst remaining within the healthy weight range). Significant changes in low density lipoprotein, triglycerides and blood pressure were not consistently reported. Conclusions A GFD alters certain cardiovascular risk factors in patients with celiac disease but the overall effect on cardiovascular risk is unclear. Further studies are warranted.

Accuracy of liver stiffness, spleen stiffness, and LS-spleen diameter to platelet ratio score in detection of esophageal varices: Systemic review and meta-analysis

Abstract: Background and aim There is increasing evidence of non-invasive measurement using elastography such liver stiffness (LS), spleen stiffness (SS), and LS-spleen diameter to platelet ratio score (LSPS) for detection of esophageal varices (EV); however, data regarding comparison between these three parameters are limited. Methods We performed a systemic review and meta-analysis of studies evaluating performance of LS, SS, and LSPS for detection of EV and high risk/clinically significant EV (HREV). Pooled sensitivity, specificity, log diagnostic odd ratio (LDOR), and area under the receiver operating characteristic curve (AUC) of LS, SS, and LSPS for detection of EV and HREV were analyzed and compared. Publication bias was assessed by Deeks' funnel plot. Results SS and LSPS were superior to LS for detection of EV with higher sensitivity (0.90 and 0.91 vs 0.85), specificity (0.73 and 0.76 vs 0.64), LDOR (3.24 and 3.35 vs 2.26), and AUC (0.899 and 0.851 vs 0.817). For HREV, SS had the highest sensitivity (0.87) followed by LS (0.85) and LSPS (0.82); however, SS had the lowest specificity (0.52), LDOR (2.09), and AUC (0.807) whereas LSPS had the highest specificity (0.77), LDOR (2.74), and AUC (0.861). Conclusion For detection of EV, we prefer using LSPS and SS over LS when available, while LS, SS, and LSPS cannot be recommended for detection of HREV due to their moderate sensitivity and specificity.

The role of exosomes on colorectal cancer: A review.

Abstract: Exosomes are extracellular microvesicles released from cells, which are involved in many biological and pathological processes, mainly because of their role in intercellular communication. Exosomes derived from colorectal cancer (CRC) cells are related to oncogenesis, tumor cell survival, chemo-resistance, and metastasis. The role of the exosomes in these processes involves the transfer of proteins, RNAs, or mutant versions of proto-oncogenes to the target cells. In recent years, great efforts have been made to identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis, and treatment response. This review focuses on recent studies on CRC exosomes, considering isolation, cargo, biomarkers, and the effects of exosomes on the development and progression of CRC, including resistance to antitumor therapy.

Oral and upper gastrointestinal Crohn's disease.

Abstract: Crohn's disease is a heterogeneous, inflammatory condition that can affect any location of the gastrointestinal tract. Proximal gastrointestinal involvement occurs in 0.5-16% of patients, and it is usually diagnosed after recognition of intestinal disease. Symptoms are often mild and nonspecific; however, upper gastrointestinal disease predicts a more severe Crohn's phenotype with a greater frequency of complications such as obstruction and perforation. Gastroscopy and biopsy is the most sensitive diagnostic investigation. There is a paucity of data examining the treatment of this condition. Management principles are similar to those for intestinal disease, commencing with topical therapy where appropriate, progressing to systemic therapy such as glucocorticoids, 5-aminosalicylic acid, immunomodulators, and biologics. Acid suppression therapy has symptomatic but no anti-inflammatory benefit for gastroduodenal and esophageal involvement. Surgical intervention with bypass, strictureplasty, or less frequently, endoscopic balloon dilation may be required for complications or failed medical therapy.

Rifaximin has minor effects on bacterial composition, inflammation, and bacterial translocation in cirrhosis: A randomized trial.

Abstract: Background & aims Decompensated cirrhosis is characterized by disturbed haemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. In a randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (±8.4), and MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed by 16S rRNA gene sequencing. Results Circulating markers of inflammation, including TNFα, interleukin-6, 10 and 18, Stromal cell-derived factor 1-α, transforming growth factor β-1 and high sensitivity CRP, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In faeces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n=34); or activated LBP (n=37) revealed no effect of rifaximin. Conclusion Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views.

Abstract: Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aβ2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles.

Oral microbiome alterations of healthy volunteers with proton pump inhibitor.

Abstract: Background and Aim Acid suppressive agents including proton pump inhibitors (PPIs) are used as first-line treatment for various acid-related gastrointestinal disorders. Although known to profoundly reduce gastric acid production, their influence on inhibition of acid secretion as part of the function of the gastrointestinal tract microbiome remains to be elucidated. The aim of the present study was to examine the effects of PPI usage on oral and gut microbiota in healthy volunteers. Methods Ten healthy adult volunteers receiving no medications were enrolled. We obtained fecal, saliva, and periodontal pocket fluid samples from the subjects before and after 4 weeks of once daily administrations of 20 mg esomeprazole. The effects of PPI administration on bacterial communities were investigated using a 16S rRNA gene sequencing method. Results Species richness (alpha diversity) was significantly different among the salivary, periodontal pocket, and fecal samples. Furthermore, the measurements for UniFrac distances, despite inter-individual variations (beta diversity), of the microbiota structure of saliva, and periodontal pocket and feces samples were clearly separated from each other. The salivary samples showed significant differences between alpha and beta diversity measurements before and after administration of the PPI for 4 weeks. Meanwhile, taxon-based analysis indicated that PPI administration raised the ratio of Streptococcus organisms in fecal samples, suggesting a potentially unfavorable effect leading to gut microbiota alteration. Moreover, alterations of the microbiota in the oral carriage microbiome along with bacterial overgrowth (Streptococcus) and decreases in distinct bacterial species (Neisseria, Veillonella) were observed. Conclusions These results suggest that PPIs cause both oral and gut microbiota alterations.

Long-term liver stiffness assessment in hepatitis C virus patients undergoing antiviral therapy: Results from a 5-year cohort study.

Abstract: BACKGROUND AND AIM Observational studies showed significant liver stiffness regression after sustained virological response, but long-term effects of antiviral therapy are still unknown. The aim of this study was to assess the magnitude of change in stiffness up to 5 years after therapy in hepatitis C patients undergoing antiviral treatment. METHODS Data of 153 patients were retrieved. Stiffness was assessed by Fibroscan at baseline, end of treatment, 6 months after treatment, and every year hereafter up to 5 years. RESULTS Seventy patients were treated with interferon-based regimens and 83 with direct antiviral agents. Baseline cirrhosis was diagnosed in 53 (34.6%) patients. Sustained virological response was achieved in 112 patients, whereas 41 were non-responders. In responders, stiffness decreased from 12.3 kPa (9-17.8) to 6.6 kPa (5.3-7.4) at 5 years. A sharper decline was observed immediately after treatment (-2.5 kPa at the end of treatment and -3.7 kPa at 6 months), while from 1 year onwards, the magnitude of stiffness decrease was progressively lower. In non-responders, stiffness showed a slight decrease at the end of treatment (from 19.2 to 18.1 kPa), then returned to baseline levels at 6 months (19.4 kPa), and finally increased over time up to 23.7 kPa (15-32.5) at 5 years. The proportion of cirrhotic patients decreased by 50% at 6 months and finally fell < 5% at 4 years after treatment. CONCLUSIONS Stiffness declines significantly after achieving response, and the magnitude of decline is greater in the first year after treatment, while it tends to plateau from 1 year onwards.

Natural history of pancreatic cystic lesions: a multicenter prospective observational study for evaluating the risk of pancreatic cancer

Abstract: Backgroud and Aim To elucidate the natural history of pancreatic cystic lesions (PCLs), including branch-duct intraductal papillary mucinous neoplasm (BD-IPMN), via mid-term follow-up analysis of a multicenter prospective observational study (NSPINAL study). Methods From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with >12 months of follow-up were analysed. Every patient was asymptomatic, and endoscopic ultrasound (EUS) was performed at the initial diagnosis to exclude high-risk individuals. Follow-up included EUS, CT or MRI at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated. Results The 664 patients (358 men) were followed for a median of 33.5 months (IQR 29). The cyst and MPD sizes were 16.6±9.3 mm and 2.3±1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were 2 resectable and 4 unresectable cases of pancreatic ductal adenocarcinoma (PDAC) and 3 cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio (SIR) for PC among PCLs was 10.0 (95% CI 3.5–16.5), and the SIR among BD-IPMN was 16.6 (95% CI 5.1–28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC. Conclusions Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect PDAC at early stages.

Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma and its implications.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver pathology that is characterized by the excessive accumulation of fat in the liver attributable to overnutrition and is strongly associated with the metabolic syndrome. Non-alcoholic steatohepatitis is the more severe form of NAFLD that is defined histologically by the presence of lobular inflammation and hepatocyte ballooning. Non-alcoholic steatohepatitis patients have a greater tendency to develop advanced liver fibrosis, cirrhosis, and HCC. This review focuses on the epidemiology of NAFLD-related HCC and its implications. NAFLD has been estimated to contribute to 10-12% of HCC cases in Western populations and 1-6% of HCC cases in Asian populations. NAFLD-related HCC is expected to increase in Asian populations, in line with the increased prevalence of NALFD similar to that of Western populations in recent years. The increasing burden of NAFLD-related HCC over time has been demonstrated in studies from both Western and Asian populations. Certain factors such as ethnicity, obesity, and diabetes mellitus appear to have an incremental effect on the risk of developing HCC among NAFLD patients. The difficulty in identifying NAFLD patients with cirrhosis and the possibility of HCC developing in noncirrhotic NAFLD patients are challenges that need to be addressed. Further understanding of these gaps may contribute to better surveillance strategies for the early detection of HCC in NAFLD patients to reduce the mortality and improve the survival of these patients.

A modified colorectal screening score for prediction of advanced neoplasia: A prospective study of 5744 subjects.

Abstract: Background and aim We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia Methods Among 5744 Chinese asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into "average risk" (AR): 0; "moderate risk" (MR): 1-2; and "high risk" (HR): 3-6 The other 1915 subjects formed a validation cohort, and the performance of the score was assessed Results The prevalence of advanced neoplasia in the derivation and validation cohorts was 54% and 60%, respectively (P = 0395) Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis A BMI cut-off at > 23 kg/m2 had better predictive capability and lower number needed to screen than that of > 25 kg/m2 Utilizing the score developed, 84%, 574%, and 342% in the validation cohort were categorized as AR, MR, and HR, respectively The corresponding prevalence of advanced neoplasia was 38%, 43%, and 93% Subjects in the HR group had 248-fold increased prevalence of advanced neoplasia than the AR group The c-statistics of the modified score had better discriminatory capability than that using predictors of APCS alone (c-statistics = 065 vs 060) Conclusions Incorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources

Honokiol attenuates diet-induced non-alcoholic steatohepatitis by regulating macrophage polarization through activating peroxisome proliferator-activated receptor γ.

Abstract: Background and aim Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. This study aimed to investigate whether honokiol could prevent NASH induced by high cholesterol and high fat (CL) diet in mice and the possible mechanism involved. Methods Mice were fed with CL diet for 12 weeks to establish a NASH model, honokiol (0.02% w/w in diet) was added to evaluate its effect on NASH. Murine peritoneal macrophages, RAW264.7 and ANA-1 cells were used to explore the possible mechanisms of honokiol on macrophage polarization. Results Mice developed NASH after fed with CL diet for 12 weeks. Honokiol supplementation alleviated insulin resistance, hepatic steatosis, inflammation and fibrosis induced by CL diet. Immunohistochemistry showed honokiol induced more M2 macrophages in livers compared with CL diet alone. Honokiol decreased M1 marker genes (TNFα, MCP-1), increased M2 marker genes (YM-1, IL-10, IL-4R, IL-13) expression in mice liver compared with CL diet. Moreover, treatment with honokiol lowered ALT and AST in serum and preserved liver from lipid peroxidation, evidenced by lowered hepatic MDA level. Honokiol has antioxidant function, as honokiol upregulated hepatic GSH and SOD level and downregulated hepatic CYP2E1 protein level. Hepatic PPARγ and its target genes were upregulated by honokiol. Furthermore, honokiol (10 μM) treatment in mouse peritoneal cells, RAW264.7 cells and ANA-1 cells led to M2 macrophage polarization, whereas a PPARγ antagonist, GW9662 abolished this effect of honokiol. Conclusions Honokiol can attenuate CL diet induced NASH and the mechanism in which possibly is polarizing macrophages to M2 phenotype via PPARγ activation.

Burden of non-alcoholic fatty liver disease in Australia

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease in the Australian population, although precise estimates of prevalence are lacking. NAFLD may progress to liver fibrosis, cirrhosis, decompensated liver disease, and liver cancer and is becoming an increasingly common indication for liver transplantation in Australia and New Zealand. There is an extrahepatic burden of NAFLD extending beyond the liver, which is manifested by an increased risk of developing cardiovascular disease, diabetes, and chronic renal impairment, all of which are common causes of morbidity in the Australian population. Early recognition of those patients at high risk of developing advanced liver disease is essential in order to target those who will benefit from intensive lifestyle modification. In this review, we present data on the epidemiology of NAFLD within Australia, its associated health burden in terms of hepatic and extrahepatic complications, common clinical presentations, and indications for treatment. We also propose a research agenda that highlights knowledge needed to improve diagnosis and management specific to the Australian context.

Temporal improvement in survival of patients with hepatocellular carcinoma in a hepatitis B virus-endemic population.

Abstract: BACKGROUND AND AIM Over the past decade, the management of hepatocellular carcinoma (HCC) and viral hepatitis has been improved. We explored survival trends and factors affecting survival of HCC in a hepatitis B virus (HBV)-endemic population. METHODS From 31 521 and 38 167 HCC registrants to the population-based national cancer registry in Korea, an HBV-endemic country, in the period of 2003-2005 and 2008-2010, we randomly sampled cohorts of 4515 and 4582 patients, respectively, for the investigation of clinical characteristics and survival. RESULTS Compared with Cohort 2003-2005, Cohort 2008-2010 had significantly better liver function (Child-Turcotte-Pugh class A, 64.2% vs 71.6%; P < 0.001) and had more advanced tumor stages (Barcelona Clinic Liver Cancer stage B-D, 45.8% vs 50.4%; P < 0.001). HBV was the predominant cause of HCC in both cohorts (62.5% vs 62.2%; P = 0.70). Cohort 2008-2010 had significantly better overall survival than Cohort 2003-2005 by age-adjusted univariate, multivariable, and propensity score-matched analyses (median survival time, 17.2 vs 28.4 months; P < 0.001). In a subcohort analysis, a consistently significant inter-cohort improvement in survival was observed only in patients with HBV-related HCC (median survival, 16.1 vs 30.4 months; P < 0.001). The annual number of patients with HCC receiving oral antiviral agents for HBV precipitously increased from 93 in 2005 to 28 520 in 2010 in the country. CONCLUSIONS The consistent improvement in survival of patients with HCC was confined to HBV-related HCC subcohort over the last decade in an HBV-endemic population. The survival improvement coincided with the exponential use of oral antiviral agents for HBV in the patients.

Usefulness of shear wave elastography as a quantitative diagnosis of chronic pancreatitis.

Abstract: BACKGROUND AND AIM Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, Endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria are based on subjective judgement. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and non-invasive method for the diagnosis of CP. METHODS Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into 4 stages using Rosemont classification (RC) and into 3 stages using Japan Pancreas Society (JPS) clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM). RESULTS PEM was significantly positively correlated with RC stage (rs = 0.54), JPS stage (rs = 0.41), and the number of EUS features (rs = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs. normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM. CONCLUSIONS CP may be diagnosed non-invasively and objectively using SW-EG without performing EUS.

Prediction of carotid intima-media thickness in obese patients with low prevalence of comorbidities by serum copper bioavailability.

Abstract: BACKGROUND AND AIM Western societies, with growing prevalence, suffer from various metabolic diseases like obesity and hepatic steatosis, better defined as non-alcoholic fatty liver disease, or cardiovascular (CV) diseases that are strictly linked to each other. The association of their occurrence with the altered homeostasis of metals is an intriguing issue. Copper in particular was identified as key player in various metabolic derangements. On these bases, we aimed at investigating the possible association of serum copper levels with an indicator of early CV risk as the intima-media thickness (IMT) of carotid artery and its predictive value in a selected population of obese patients. METHODS We performed a cross-sectional study recruiting 100 obese patients characterized by a low prevalence of comorbidities. Ultrasound investigation for hepatic steatosis and IMT evaluation were performed. Serum samples were collected and then analyzed through atomic absorption spectrometry to evaluate their copper content. Possible correlations between copper bioavailability and biochemical, clinical, and anthropometric characteristics of patients were sought. RESULTS Age negatively predicted copper serum levels of patients (P = 0.009). However, the most interesting finding is the negative prediction of IMT by the copper serum levels (t = -2.23, P = 0.028, least absolute deviations regression). Factor analysis confirmed the aforementioned inverse correlation and highlighted the strong inverse correlation between smoking and copper serum levels. CONCLUSION Our data show that an altered copper bioavailability predicts early atherosclerosis as main CV risk in obese patients with hepatic steatosis detected by ultrasound, shedding some light in this pathological scenario.