Showing papers in "Journal of Gastroenterology and Hepatology in 2016"

Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis.

Abstract: Background and Aim: The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography. Methods: Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta-analysis. Results Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5 years (range: 3–14.7 years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80–2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43–1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71–2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76–1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5 years (range: 3–11 years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72–1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89–2.07) for GGT, and 3.22 (95% CI, 3.05–3.41) for ultrasonography, respectively. Conclusions: Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up.

Trends in esophageal cancer survival in United States adults from 1973 to 2009: A SEER database analysis.

Abstract: BACKGROUND AND AIM The rise in incidence of esophageal cancer (EC) in the USA over the last four decades has been well documented; however, data on trends in long-term survival and impact on modern therapies associated with survival are lacking. METHODS The Surveillance, Epidemiology, and End Results database was queried to identify patients with confirmed EC. Cox proportional hazard regression was used to determine independent mortality factors. RESULTS Of 93 167 patients diagnosed with EC between 1973 and 2009, 49% had a histologic diagnosis of esophageal adenocarcinoma (EAC). There was an increase (almost double) in the proportion of patients with adenocarcinoma from the 1970s to 2000s (n = 2,350; 35% to n = 32,212; 61%, P < 0.001). Surgery was performed for localized disease in a majority of EC regardless of type (n = 46 683; 89%). Use of surgical treatment increased significantly over the study period (49% to 64%, P < 0.001). There was also an increase in overall median survival (6 months versus 10 months, P < 0.001) and 5-year survival rate (9% to 22%, P < 0.001). Median survival increased consistently for EAC and squamous cell carcinoma (SCC) until the 1990s. After this period, median survival of EAC continued to increase more rapidly while SCC remained relatively stable. CONCLUSION A significant survival improvement in esophageal cancer was seen from 1973 to 2009, largely because of earlier detection at a curative stage and greater utilization of treatment modalities (especially surgery). Despite the rising prevalence, patients with EAC have better long-term survival outcomes than those SCC.

Usefulness of albumin-bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma.

Abstract: Background and Aim: The Child–Pugh classification has some non-objective factors, with chronic hepatitis indistinguishable from early liver cirrhosis in Child–Pugh A. We retrospectively evaluated the efficacy of albumin–bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for grading hepatocellular carcinoma (HCC) patients based on hepatic function and predicting their prognosis. Method: From 2000 to 2014, 2584 naive HCC [69.0 ± 9.8 years old, 1850 men, 734 female, Child–Pugh class A:B:C = 1871:558:155] were enrolled. TNM staging was determined using the classification of the Liver Cancer Study Group of Japan and ALBI grade, instead of Child–Pugh classification (ALBI with TNM score: ALBI-T score) (Table 1), and is similar to the Japan Integrated Staging (JIS) score. We retrospectively compared ALBI-T and JIS scores in these patients. Results: Of patients classified as Child–Pugh A (n = 1871), 1285 with 5 points were divided into 858 with ALBI grade 1 and 427 with grade 2, while 586 with 6 points were divided into 53 with grade 1 and 533 with grade 2. The ratio of ALBI grade 2 patients with a Child–Pugh score of 6 points (91.0%) was similar to that of those with 7 points (91.8%). Patients with a lower ALBI-T score (0–5 points) showed a better median survival time than those with a corresponding lower JIS score [137.7:83.2:53.4:27.4:5.0:1.4 vs 97.6:74.9:39.7:15.0:4.0:1.0 months]. Conclusion: Albumin–bilirubin grade was found to be superior for distinguishing patients with better hepatic function. ALBI-T scoring may be a better total prognostic scoring system for predicting survival of Japanese patients with HCC.

Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease.

Abstract: Background and Aim Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters. Methods All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis 66%. Results Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis 310 dB/m. Conclusion The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients.

LncRNA‐ATB mediated E‐cadherin repression promotes the progression of colon cancer and predicts poor prognosis

Abstract: BACKGROUND Long non-coding RNA-activated by TGF-β (lncRNA-ATB) promotes the invasion-metastasis cascade in hepatocellular carcinoma via downregulating E-cadherin (E-cad) and inducing epithelial-to- mesenchymal transition (EMT) and is clinically significant in human colon cancer. However, its molecular mechanisms in colon cancer progression remain unclear. This study aimed to elucidate the role of lncRNA-ATB and its clinical value in colon cancer. METHODS Expression levels of lncRNA-ATB in colon cancer tissues and colon cancer cell lines were evaluated using quantitative real-time polymerase chain reaction. The clinicopathological significance and prognostic value of lncRNA-ATB were investigated, and roles of lncRNA-ATB in regulating E-cad and other EMT-related markers expression and colon cancer progression were evaluated in vitro. Expression levels of lncRNA-ATB and E-cad in human plasma were evaluated. RESULTS Long non-coding RNA-activated by TGF-β was upregulated in colon cancer tissues compared with adjacent mucosa (P < 0.001). LncRNA-ATB levels were also higher in metastatic cancer tissues (P < 0.001). Among the three highly invasive colon cancer cell lines, lncRNA-ATB levels were relatively higher with concurrent low levels of E-cad compared with levels in the three low-invasive cell lines. LncRNA-ATB expression correlated with pN stage (P < 0.01) and American Joint Committee on Cancer stage (P < 0.01). Striking differences were observed in overall survival and disease-free survival in cases with both high lncRNA-ATB expression and low E-cad expression. Reduction of lncRNA-ATB increased expression of epithelial markers E-cad, ZO-1, and decreased expression of mesenchymal markers ZEB1 and N-cadherin (N-cad), and significantly influenced colon cancer cell progression. Plasma lncRNA-ATB was upregulated in colon cancer patients one month after surgery (P < 0.05). CONCLUSIONS Long non-coding RNA-activated by TGF-β may act on colon tumorigenesis by suppressing E-cad expression and promoting EMT process, and lncRNA-ATB inhibition may provide a promising therapeutic option for suppressing colon cancer progression.

Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease.

Abstract: Background and aim The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial. There is sparse literature on the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The present study evaluated the relationship of SIBO with expression of TLR signaling genes in patients with NAFLD. Methods A total of 142 subjects composed of NAFLD (n = 60, mean age 38.7 ± 10.4 years), chronic viral hepatitis (CVH) (n = 32, mean age 39.5 ± 10.6 years), and healthy volunteers (n = 50, mean age 36.56 ± 4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in 32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA expression of TLR4, CD14, TLR2, NF-κβ, and MD2 and protein expression of TLR4 and TLR2 were studied in 64 patients (NAFLD = 32, CVH = 32) by RT-PCR and immunohistochemistry, respectively. Serum levels of TNF-α, adiponectin, insulin, and endotoxins were also evaluated. Results Small intestinal bacterial overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with Escherichia coli as the predominant bacterium. In comparison with those without SIBO, patients with SIBO had significantly higher endotoxin levels and higher CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients with NASH had significantly higher endotoxin levels and higher intensity of TLR4 protein expression in comparison with patients without NASH. Serum levels of TNF-α, endotoxins, and insulin were significantly higher and of adiponectin lower in NAFLD in comparison with CVH and healthy volunteers. Conclusions Our study provides the first direct evidence of role of SIBO and endotoxemia and its relation with TLR signaling genes and liver histology in patients with NAFLD.

Nonalcoholic steatohepatitis is strongly associated with sarcopenic obesity in patients with cirrhosis undergoing liver transplant evaluation

Abstract: Background Sarcopenia is the most common complication of cirrhosis and adversely affects quality of life and outcomes before, during, and after liver transplantation. We studied predictors of sarcopenia and sarcopenic obesity in patients with cirrhosis undergoing liver transplant (LT) evaluation. Methods A retrospective analysis of 207 adult cirrhotic patients that underwent LT from January 2008 to December 2013 was performed at our institution. Results Two hundred seven patients were evaluated, 68% were male with a mean age of 54 ± 8 years. The most common etiology of cirrhosis was alcoholic liver disease (38.6%), followed by chronic hepatitis C (38.2%), nonalcoholic steatohepatitis (NASH) (21.7%), and hepatocellular carcinoma (HCC) (24.6%). The mean body mass index of the cohort was of 30.1 ± 5.7 kg/m2. Forty-eight percent of these patients were obese. Of the 207 patients, 88% had computed tomographic (CT) scans within 90 days before transplant; of these, 59% had sarcopenia found during LT evaluation. Of the patients with pretransplant sarcopenia, 59 had CT scan at 6 months posttransplant and 56 (95%) remained sarcopenic. Of the 56 patients who had sarcopenia at 6 months, 31 had available CT scans at 1 year, and 100% persisted with sarcopenia. These 31 subjects had a mean skeletal muscle index of 35 at 6 months and 36 at 1 year. SO was found in 41.7% of our patients. On multivariable regression analysis, obesity and age were found to be independently associated with pretransplant sarcopenia after controlling for gender and alcohol liver disease diagnosis (P = 0.00001, odds ratio [OR] 0.22, and P = 0.008, OR 2.0, respectively). A multivariable logistic regression analysis found that NASH as cause of cirrhosis and model of end-stage liver disease score are independent predictors of sarcopenic obesity after controlling for age, gender, alcoholic liver disease diagnosis, and HCC (P = 0.014 and 0.038, respectively; 95% confidence interval, 1.44–25.26 and 1.00–1.15, respectively; OR 6.03, 1.08, respectively). Conclusions Sarcopenia and sarcopenic obesity is seen in a significant number of patients with cirrhosis undergoing LT evaluation. Sarcopenia progresses after LT initially and does not recover at least within the first year after surgery. Obesity is an independent predictor of pretransplant sarcopenia and NASH was associated with 6-fold increased risk of having sarcopenic obesity in cirrhotic patients in our cohort.

Integration of albumin–bilirubin (ALBI) score into Barcelona Clinic Liver Cancer (BCLC) system for hepatocellular carcinoma

Abstract: Background and Aims The albumin–bilirubin (ALBI) grade is a recently reported, simpler, more objective, and evidence-based alternative to the Child–Pugh (CP) score for hepatocellular carcinoma (HCC). We aimed to study whether ALBI grade could substitute for CP score in Barcelona Clinic Liver Cancer (BCLC) for HCC. Methods An international multicentre cohort (n = 3696) was accrued to compare the prognostic performance of the CP-based and ALBI-based BCLC system, in terms of homogeneity, discriminatory ability, and monotonicity of gradients that were numerically reflected by homogeneity likelihood, linear trend chi-squares, and c-indices, respectively. Results The ALBI grade performed as well as CP score when integrated into the BCLC staging system in terms of predicting clinical outcome of HCC regardless of regions, etiology, and treatment options. CP-based and ALBI-based BCLC systems were highly concordant with weighted kappa value of 0.917. All restaged patients showed significantly different clinical outcomes compared with their original stage classification. In particular, ALBI-based BCLC upstaged 83 (2.2%) patients from lower CP-based BC LC stages to ALBI-based BCLC stage D, whose median overall survival was only 3 months. Conclusions The overall prognostic performance of ALBI-based and CP-based BCLC systems was similar. It also potentially allows more precise patient selection for clinical trials on systemic agents.

Asia Pacific Consensus Statements on Crohn's disease. Part 1: Definition, diagnosis, and epidemiology: (Asia Pacific Crohn's Disease Consensus--Part 1).

Abstract: Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology with the goal of developing best management practices, coordinating research, and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis, and management of Crohn's disease. The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses, and treatment availability. It does not intend to be all comprehensive and future revisions are likely to be required in this ever-changing field.

MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis.

Abstract: Background and Aim: Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory disorder of the large intestine. Mucosal associated invariant T (MAIT) cells are a member of innate-like lymphocytes found abundantly in the mucosal tissue. The contribution of MAIT cells in the pathogenesis of UC is still unclear; therefore, this study aimed at investigating the role of these cells in patients with UC. Methods: The frequency of MAIT cells, as well as the production of cytokines and expression levels of activation markers by these cells in the peripheral blood of UC patients and healthy controls, was analyzed by flow cytometry. MAIT cells were also quantified in colon biopsies of UC patients using a confocal microscope. Results: There was a significant reduction in MAIT cell frequency in the peripheral blood of UC patients compared with healthy controls (P < 0.0001). MAIT cells from UC patients secreted more interleukin (IL)-17 than healthy controls (P < 0.05). The expression levels of CD69 on these cells were correlated with disease activity and endoscopic scores and plasma levels of IL-18. Furthermore, MAIT cells increased in the inflamed mucosa, and their frequency was correlated with clinical and endoscopic disease activity in UC patients. Conclusions: The findings from this study indicate that MAIT cells could be associated with UC and may serve as potential biomarkers or therapeutic targets in UC.

Red pitaya betacyanins protects from diet-induced obesity, liver steatosis and insulin resistance in association with modulation of gut microbiota in mice.

Abstract: Background and Aim Growing evidence indicates that gut microbiota contributes to obesity and its related metabolic disorders. Betacyanins possess free radical scavenging and antioxidant activities, suggesting its potential beneficial effects on metabolic diseases. The present study aimed to investigate the metabolic effect of red pitaya (Hylocereus polyrhizus) fruit betacyanins (HPBN) on high-fat diet-fed mice and determine whether the beneficial effects of HPBN are associated with the modulation of gut microbiota. Methods Thirty-six male C57BL/6J mice were divided into three groups and fed low-fat diet (LFD), high-fat diet (HFD), or high-fat diet plus HPBN of 200 mg/kg for 14 weeks. Sixteen seconds rRNA sequencing was used to analyze the composition of gut microbiota. Results Our results indicated that administration of HPBN reduced HFD-induced body weight gain and visceral obesity and improved hepatic steatosis, adipose hypertrophy, and insulin resistance in mice. Sixteen seconds rRNA sequencing performed on the MiSeq Illumina platform (Illumina, Inc., San Diego, CA, USA) showed that HPBN supplement not only decreased the proportion of Firmicutes and increased the proportion of Bacteroidetes at the phylum level but also induced a dramatic increase in the relative abundance of Akkermansia at the genus level. Conclusions Red pitaya betacyanins protect from diet-induced obesity and its related metabolic disorders, which is associated with improved inflammatory status and modulation of gut microbiota, especially its ability to decrease the ratio of Firmicutes and Bacteroidetes and increase the relative abundance of Akkermansia. The study suggested a clinical implication of HPBN in the management of obesity, non-alcoholic fatty liver disease, and type 2 diabetes.

Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials.

Abstract: Background and aims Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE. Methods We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias. Results Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23). Conclusions Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE.

Percutaneous thermal ablation for primary hepatocellular carcinoma: A systematic review and meta-analysis.

Abstract: Background and Aim: Percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA) are both widely available curative treatments for hepatocellular carcinoma Despite significant advances, it remains unclear which modality results in better outcomes This meta-analysis of randomized controlled trials (RCT) and observational studies was undertaken to compare the techniques in terms of effectiveness and safety Methods: Electronic reference databases (Medline, EMBASE and Cochrane Central) were searched between January 1980 and May 2014 for human studies comparing RFA and MWA The primary outcome was the risk of local tumor progression (LTP) Secondary outcomes were complete ablation (CA), overall survival, and major adverse events (AE) The ORs were combined across studies using the random-effects model Results: Ten studies (two prospective and eight retrospective) were included, and the overall LTP rate was 136% (176/1298) There was no difference in LTP rates between RFA and MWA [OR (95% CI): 101(067–150), P = 09] The CA rate, 1- and 3-year overall survival and major AE were similar between the two modalities (P > 005 for all) In subgroup analysis, there was no difference in LTP rates according to study quality, but LTP rates were lower with MWA for treatment of larger tumors [188(110–323), P = 002] There was no significant publication bias or inter-study heterogeneity (I2 01) observed in any of the measured outcomes Conclusion: Overall, both RFA and MWA are equally effective and safe, but MWA may be more effective compared to RFA in preventing LTP when treating larger tumors Well-designed, larger, multicentre RCTs are required to confirm these findings

Hepatobiliary and pancreatic: Comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients.

Abstract: Background and Aim Chinese herbal medicine (CHM), as well as Western medicine (WM), is an important cause of drug-induced liver injury (DILI). However, the differences between CHM and WM as agents implicated in liver injury have rarely been reported. Methods Overall, 1985 (2.05%) DILI cases were retrospectively collected from the 96 857 patients hospitalized because of liver dysfunction in the 302 Military Hospital between January 2009 and January 2014. Results In all the enrolled patients with DILI, CHM was implicated in 563 cases (28.4%), while 870 cases (43.8%) were caused by WM and the remaining patients (27.8%) by the combination of WM and CHM. Polygonum multiflorum was the major implicated CHM. Compared with WM, the cases caused by CHM showed more female (51 vs 71%, P < 0.001) and positive rechallenge (6.1 vs 8.9%, P = 0.046), a much greater proportion of hepatocellular injury (62.2 vs 88.5%, P < 0.001), and a higher mortality (2.8 vs 4.8%, P = 0.042); however, no differences in the rates of chronic DILI and ALF were found (12.9 vs 12.4%, P = 0.807; 7.6 vs 7.6%, P = 0.971). Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4 and 60.3%, all P < 0.001). Conclusions The causal relationship between CHM and liver injury is much complex, and the clinical characteristics of DILI caused by CHM differ from those caused by WM.

Incomplete type of intestinal metaplasia has the highest risk to progress to gastric cancer: results of the Spanish follow-up multicenter study.

Abstract: Background and aim In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence. Methods A follow-up study was carried-out including 649 patients, diagnosed with PL between 1995-2004 in 9 participating hospitals from Spain, and who repeated the biopsy during 2011-2013. Medical information and habits were collected through a questionnaire. Based on morphology, IM was sub-classified as complete (small intestinal type, CIM) and incomplete (colonic type, IIM). Analyses were done using Cox (HR) models. Results At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34% IIM, and 4% dysplasia. Mean follow-up was 12 years. 24 patients (3.7%) developed a gastric adenocarcinoma during follow-up. The incidence rate of GC was 2.76 and 5.76 per 1,000 person-years for those with CIM and IIM, respectively. The HR of progression to CG was 2.75 (95% CI 1.06-6.26) for those with IIM compared with those with CIM at baseline, after adjusting for sex, age, smoking, family history of GC and use of NSAIDs. Conclusions IIM is the PL with highest risk to progress to GC. Sub-typing of IM is a valid procedure for the identification of high risk patients that require more intensive surveillance.

Performance of magnetic resonance elastography in primary sclerosing cholangitis.

Abstract: Background and Aim: Liver stiffness (LS) measured by magnetic resonance elastography (MRE) is emerging as an important biomarker in chronic liver diseases. We examined the diagnostic performance of MRE, factors associated with an increased LS and the prognostic value of LS as measured by MRE among patients with primary sclerosing cholangitis (PSC). Methods: We performed a retrospective review of 266 patients with PSC to examine whether LS was associated with the primary endpoint of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy). The ability of MRE to differentiate stages of fibrosis was examined in a subset of patients who underwent a liver biopsy (n = 20). Results: An LS of 4.93 kPa was the optimal point to detected F4 fibrosis (sensitivity, 1.00; 95% confidence interval (CI), 0.40–1.00; specificity, 0.94; 95%CI, 0.68–1.00). While a serum alkaline phosphatase 6.0 kPa (respectively). Conclusion: Magnetic resonance elastography is able to detect cirrhosis with high specificity and an alkaline phosphatase <1.5 times the upper limit of normal makes the presence of advanced LS unlikely. Moreover, LS obtained by MRE is predictive of hepatic decompensation in PSC.

Prevalence of celiac disease in Asia: A systematic review and meta-analysis.

Abstract: Background and Aim Celiac disease (CD) is emerging in Asia. While a few population-based studies from Asia have reported a prevalence of CD from 0.1% to 1.3%, the exact prevalence of CD in Asia is not known. We conducted a systematic review and meta-analysis to estimate the prevalence of CD in Asia. Methods On search of literature, we found 1213 articles, of which 18 articles were included. Diagnosis of CD was based on European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Results Pooled sero-prevalence of CD in Asia was 1.6% in 47 873 individuals based on positive anti-tissue transglutaminase and/or anti-endomysial antibodies. Pooled prevalence of biopsy proven CD in Asia was 0.5% in 43 955 individuals. The prevalence of CD among women was higher than in men (0.5% vs 0.4%, P = 0.04). The pooled prevalence of CD was 0.3% in Iran, 0.5% in Turkey, 0.6% in India, and 0.7% in Israel. The pooled prevalence of CD was significantly higher in Israel and India as compared with that in Iran. Conclusions Celiac disease is not uncommon in Asia, and the sero-prevalence and prevalence of CD in Asia are 1.6% and 0.5%, respectively. The prevalence of CD varies with gender and geographic location. There is a need for population-based prevalence studies in many Asian countries to properly estimate the burden of CD in Asia.

Features of electrocoagulation syndrome after endoscopic submucosal dissection for colorectal neoplasm

Abstract: BACKGROUND AND AIMS Endoscopic submucosal dissection (ESD) is a promising treatment for large gastrointestinal superficial neoplasms, although it is technically difficult, and perforation and delayed bleeding are well-known adverse events. However, there have been no large studies about electrocoagulation syndrome after colorectal ESD. The aim of this study was to evaluate the incidence and clinical significant risk factors of post-ESD coagulation syndrome (PECS). METHODS This was a retrospective cohort study conducted in a referral cancer center. A total of 336 patients with colorectal neoplasms (143 adenomas or serrated lesions and 193 carcinomas) underwent ESD from January 2011 to June 2013. Incidence, outcome, and factors associated with occurrence of PECS were investigated. RESULTS Occurred in 32 patients (9.5%). The median time until PECS was 15.5 h, and the median period of PECS was 32.5 h. Fever (≥37.6 °C) after ESD was found in 41% of the PECS group and 9% of the non-PECS group (P < 0.001). All PECS cases were managed conservatively. On multivariate analysis, female patients (odds ratio [OR] = 3.2, P = 0.002), lesion location at ascending colon and cecum (OR = 3.5, P = 0.001), and resected specimen ≥40 mm (OR = 2.1, P = 0.05) were independent risk factors for PECS. CONCLUSIONS Occurred in 32 patients (9.5%) with colorectal ESD; however, all cases had a good outcome with conservative management. Female sex, tumor location at the ascending colon and cecum, and resected specimen ≥40 mm were independently significant risk factors for PECS.

Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis

Abstract: Background and Aim Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection. Methods Initial or additional surgery with nodal dissection was performed in 653 T1 carcinoma cases. Clinicopathological factors were retrospectively analyzed with respect to nodal metastasis. The status of the muscularis mucosae (MM grade) was defined as grade 1 (maintenance) or grade 2 (fragmentation or disappearance). The lesions were then stratified based on the risk of nodal metastasis. Results Muscularis mucosae grade was associated with nodal metastasis (P = 0.026), and no patients with MM grade 1 lesions had nodal metastasis. Significant risk factors for nodal metastasis in patients with MM grade 2 lesions were attribution of women (P = 0.006), lymphovascular infiltration (P < 0.001), tumor budding (P = 0.045), and poorly differentiated adenocarcinoma or mucinous carcinoma (P = 0.007). Nodal metastasis occurred in 1.06% of lesions without any of these pathological factors, but in 10.3% and 20.1% of lesions with at least one factor in male and female patients, respectively. There was good inter-observer agreement for MM grade evaluation, with a kappa value of 0.67. Conclusions Stratification using MM grade, pathological factors, and patient sex provided more appropriate indication for additional surgery with lymph node dissection after endoscopic treatment for T1 colorectal carcinomas.

Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma.

Abstract: Background and Aim Solid demonstrations of superior efficacy of drug-eluting beads transarterial chemoembolization with respect to conventional chemoembolization in hepatocellular carcinoma patients are lacking. The aim of the study was to compare these two techniques in two large cohorts of unresectable hepatocellular carcinoma patients. Methods A single center series of 249 early/intermediate hepatocellular carcinoma patients who underwent “on demand” chemoembolization in the period 2007–2011 was analyzed. Overall survival, time to progression, tumor response rate, and safety were compared between 104 patients who underwent conventional chemoembolization and 145 who underwent drug-eluting beads chemoembolization. Time-to-event data were analyzed using the Cox univariate and multivariate regression. Results The two cohorts resulted balanced for liver function and tumor stages. Objective response rate was 85.3% after conventional and 74.8% after drug-eluting beads chemoembolization (P = 0.039), and median time to progression was 17 (95% confidence interval: 14–21) versus 11 months (9–12), respectively (P < 0.001). Treatment regimen was the sole independent predictor of progression at multivariate analysis (hazard ratio = 2.01; 1.45–2.80; P < 0.001). Median survival was 39 (32–47) and 32 (24–39) months in the two groups, respectively (hazard ratio = 1.33; 0.94–1.87; P = 0.10), but conventional chemoembolization was significantly associated with a survival advantage in patients with bilobar neoplasia, portal hypertension and alpha fetoprotein above normal limits. No significant differences in severe adverse events were found. Conclusion In a large series of Western hepatocellular carcinoma patients, drug-eluting beads chemoembolization with 100–300 µm particles did not seem to improve survival in comparison with conventional chemoembolization, which in turn provided better tumor responses and time to progression.

Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis

Abstract: Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in Western societies. Despite its significance, there are no well-proven pharmacological treatments. Two novel classes of potential pharmacotherapies are the glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I), collectively known as incretin-based therapies. These have several metabolic and anti-inflammatory actions that may be of benefit in NAFLD. The aim of this meta-analysis was to evaluate their efficacy via a structured retrieval and pooled analysis of relevant studies. Methods: Studies were sourced from electronic databases and meeting abstracts. Main inclusion criteria were original studies investigating treatment of adults with NAFLD using GLP-1 RA/DPP-4I. Key outcomes were a change in serum alanine transaminase (ALT), as a marker of liver inflammation, and improvement in disease status measured by imaging or histology. Results: Initial searching retrieved 1357 peer-reviewed articles and abstracts. Four studies met all inclusion and exclusion criteria. There were a total of 136 participants with NAFLD and concomitant type 2 diabetes mellitus (T2DM). Meta-analysis (random-effects model) revealed a significant decrease in serum ALT following treatment (mean reduction 14.1 IU/L, 95% confidence intervals [CI] 8.3–19.8, P < 0.0001). In two studies with imaging and tissue data, treatment was found to significantly reduce steatosis, inflammation, and fibrosis. Conclusion: The significant decrease in a key biochemical marker of hepatic inflammation following treatment with incretin-based therapies, as well as improvements in imaging and histology, suggests these agents may be effective options for managing NAFLD with comorbid T2DM.

Early TIPS versus endoscopic therapy for secondary prophylaxis after management of acute esophageal variceal bleeding in cirrhotic patients: a meta-analysis of randomized controlled trials.

Abstract: BACKGROUND AND AIMS American College of Gastroenterology and American Association for the Study of Liver Disease guidelines recommend endoscopic and pharmacologic treatment for esophageal variceal bleed. Transjugular intrahepatic portosystemic shunt (TIPS) placement is reserved for cases of therapeutic failure. Several studies have suggested improved prevention of rebleeding and improved survival without excess hepatic encephalopathy in patients who receive TIPS within the first 5 days after bleeding (early TIPS). In this meta-analysis, we evaluated the safety and efficacy of early TIPS versus endoscopic therapy for secondary prophylaxis after acute esophageal variceal bleeding in cirrhotic patients. METHODS Pubmed, Medline, Embase, ClinicalTrials.gov, and ISI Web of Science were searched for randomized controlled trials that compared early TIPS to endoscopic therapy. The primary outcome was mortality at 1 year; secondary outcomes were rebleeding and hepatic encephalopathy at 1 year. RESULTS Nine randomized controlled trials involving 608 cirrhotic patients were identified. Early TIPS was associated with a significant risk reduction in 1-year mortality (RR, 0.68; 95% CI, 0.49-0.96; P = 0.03) and 1-year incidence of variceal rebleeding (RR, 0.28; 95% CI, 0.20-0.40; P < 0.001) without significant heterogeneity among studies (I(2) = 30% and 47%, respectively). No significant difference in the incidence of hepatic encephalopathy at 1 year was observed (RR, 1.36; 95% CI, 0.72-2.56; P = 0.34); however, there was significant heterogeneity among studies (I(2) = 68%). CONCLUSION TIPS placed within 5 days after a major esophageal variceal hemorrhage is superior to endoscopic treatment in reducing subsequent bleeding. Early TIPS placement is also associated with superior 1-year survival without significantly increasing the incidence of hepatic encephalopathy.

Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large-scale, long-term cohort study.

Abstract: Background: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. Methods: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. Results: During the observation period (median 50 months: range 13–224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17–141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3–6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8–50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6–7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9–16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC. Conclusions: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis.

Abstract: Background Key aims of treatment of coeliac disease are to heal the intestinal mucosa and correct nutritional abnormalities. Aim We aim to determine prospectively the degree of success and time course of achieving those goals with a gluten-free diet. Methods Ninety-nine patients were enrolled at diagnosis and taught the diet. The first 52 were reassessed at 1 year and 46 at 5 years, 25 being assessed at the three time points regarding dietary compliance (dietitian-assessed), coeliac serology, bone mineral density and body composition analysis by dual energy X-ray absorptiometry, and intestinal histology. Results Mean age (range) was 40 (18–71) years and 48 (76%) were female. Dietary compliance was very good to excellent in all but one. Tissue transglutaminase IgA was persistently elevated in 44% at 1 year and 30% at 5 years and were poorly predictive of mucosal disease. Rates of mucosal remission (Marsh 0) and response (Marsh 0/1) were 37% and 54%, and 50% and 85% at 1 and 5 years, respectively. Fat mass increased significantly over the first year in those with normal/reduced body mass index. Lean body mass indices more slowly improved irrespective of status at diagnosis with significant improvement at 5 years. Bone mass increased only in those with osteopenia or osteoporosis, mostly in year 1. Conclusion Dietary compliance is associated with a high chance of healing the intestinal lesion and correction of specific body compositional abnormalities. The time course differed with body fat improving within 1 year, and correction of the mucosal lesion and improvement in lean mass and bone mass taking longer.

Meta‐analysis: The diagnostic efficacy of chromoendoscopy for early gastric cancer and premalignant gastric lesions

Abstract: Background and Aim:Chromoendoscopy (CE) is widely used in the diagnosis of early gastric cancer (EGC) and premalignant gastric lesions (PGLs). We conducted a meta-analysis to evaluate the diagnostic efficacy of CE for EGC and PGLs.Methods:We searched PubMed/MEDLINE, EMBASE, and the Cochrane

Microbiology and resistance in first episodes of spontaneous bacterial peritonitis: implications for management and prognosis.

Abstract: Purpose International guidelines for antibiotic treatment of spontaneous bacterial peritonitis (SBP) are based on studies conducted decades ago and do not reflect regional differences of bacterial epidemiology. Methods We retrospectively analyzed epidemiology of agents, antibiotic resistance patterns, and survival in liver cirrhosis patients with their first episode of SBP during the years 2007-2013. Results Of the 311 patients included, 114 patients had a positive ascites culture, and 197 had an ascitic neutrophil count >250 μL. Gram-positive bacteria (47.8%) were more frequently found than Gram-negatives (44.9%), fungi in 7.2%. Enterobacter spp. (40.6%), Enterococcus spp. (26.1%), and Staphylcoccus spp. (13.8%) were the most frequently isolated agents. Third-generation cephalosporins covered 70.2% of non-nosocomial and 56.3% of nosocomial-acquired SBP cases.When SBP was diagnosed by a positive ascitic culture, survival was highly significantly reduced (mean: 13.9 ± 2.9 months; 95% confidence interval [CI]: 8.1-19.8) compared with culture-negative SBP patients (mean: 44.1 ± 5.4 months; 95% CI: 33.4-54.9; P = 0.000). Along with model of end-stage liver disease score and intensive care unit contact, a positive ascites culture remained an independent risk factor associated with poor survival (odds ratio: 1.49; 95% CI: 1.09-2.03) in multivariate analysis; piperacillin/tazobactam proved to be an adequate antibiotic for nosocomial and non-nosocomial SBP in 85.1% and 92.5%, respectively. SBP infection with Enterococcus spp. was associated with poor patient survival (P = 0.048). Conclusions Third-generation cephalosporins have poor microbial coverage for treatment of SBP. Current guidelines need to adapt for the emerging number of Gram-positive infectious agents in SBP patients.

The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma.

Abstract: Objective This study determined the expression of microRNA-1 in esophageal squamous cell carcinoma (ESCC) tissue and cell lines to evaluate its effects on clinicopathological parameters and its target genes LASP1 and TAGLN2. Methods The expression of miR-1, lasp1, and tagln2 was detected in 55 ESCC tissues and adjacent normal tissues by reverse transcription–polymerase chain reaction (RT-PCR). The association between miR-1, lasp1, and tagln2 expression and clinicopathological characteristics was observed. MicroRNA-1 (mimics-miR-1) and its inhibitor (Inhibitor-miR-1) were transfected into esophageal cancer cells KYSE 510 and Eca 109; cell proliferation, migration, and invasion assays were carried out. Plasmid construction and dual-luciferase reporter assay were also carried out to indicate whether LASP1 and TAGLN2 were miR-1 target genes. The expression of LASP1 and TAGLN2 was detected with Western blot methods in cell lines, by immunohistochemistry in ESCC tissue. Results The gene expression level of microRNA-1 in cancer tissues was significantly lower than that in adjacent normal tissues (P < 0.01). The expression of miR-1 in ESCC was correlated with involvement of lymph nodes (P = 0.002), histologic classification (P = 0.000), and vessel invasion (P = 0.022). The expression of lasp1 and tagln2 increased in cancer tissues compared with in adjacent normal tissues (P < 0.05). MiR-1 suppresses the cell growth, migration, and invasion in vitro. The expression of LASP1 and TAGLN2 decreased in mimics-miR-1 transfected cells, and increased in inhibitor-miR-1 transfected cells. Luciferase reporter assay confirmed that LASP1 and TAGLN2 mRNA actually had the target sites of miR-1. Conclusions miR-1 suppresses cell proliferation, invasiveness, metastasis, and progression of ESCC by binding its targeted genes LASP1 and TAGLN2.

Acute on chronic liver failure because of acute hepatic insults: Etiologies, course, extrahepatic organ failure and predictors of mortality.

Abstract: BACKGROUND AND AIM Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome. METHODS In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated. RESULTS Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol (n = 85/40%), HBV(n = 52/24%), and cryptogenic(n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies;P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly(P = 0.001). CONCLUSIONS Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor.

Fecal calprotectin is a clinically relevant biomarker of mucosal healing in patients with quiescent ulcerative colitis.

Abstract: Background and Aim: Calprotectin is an abundant protein in neutrophils, which infiltrate the mucosa during inflammation. Fecal calprotectin (FC) level has shown correlation with disease activity in ulcerative colitis (UC) patients. Additionally, FC level is expected to indicate mucosal healing (MH). This study was to see the significance of FC for predicting MH in patients with quiescent UC. Methods: A total of 112 patients with quiescent UC were included. After taking blood and stool samples, patients underwent total colonoscopy, and the Mayo endoscopic subscore was recorded. FC was measured by fluorescence enzyme immunoassay. C-reactive protein, hemoglobin, erythrocyte sedimentation rate, and serum albumin were measured as conventional biomarkers. MH was defined as Mayo 0 or 0 and 1, and receiver–operator characteristic analyses were undertaken to determine the significance levels of measurements. Results: Data from 105 patients were available. Eleven patients showed Mayo ≥ 2. The median (interquartile range) of FC level of all patients was 115 µg/g (45.4–420). The area under the curve (AUC) in receiver operator characteristic analysis of FC to predict Mayo 0 and 1 was 0.869 with a cut-off value of 200 µg/g yielding 67% sensitivity and 91% specificity, which were the best among all biomarkers. However, the power of FC to predict Mayo 0 was modest; the AUC was 0.639 and cut-off value 194 µg/g with 71% sensitivity and 58% specificity. Conclusions: Based on the findings of this study, we believe that FC is a clinically relevant biomarker of MH in patients with quiescent UC. Other favorable features of FC test include feasibility and non-invasiveness.

Asian consensus statements on endoscopic management of walled-off necrosis Part 1: Epidemiology, diagnosis, and treatment.

Abstract: Walled-off necrosis (WON) is a relatively new term for encapsulated necrotic tissue after severe acute pancreatitis. Various terminologies such as pseudocyst, necroma, pancreatic abscess, and infected necrosis were previously used in the literature, resulting in confusion. The current and past terminologies must be reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy was introduced as a treatment option and is now preferred over surgical necrosectomy when the expertise is available. However, high-quality evidence is still lacking, and there is no standard management strategy for WON. The consensus meeting aimed to clarify the diagnostic criteria for WON and the role of endoscopic interventions in its management. In the Consensus Conference, 27 experts from eight Asian countries took an active role and examined key clinical aspects of WON diagnosis and endoscopic management. Statements were crafted based on literature review and expert opinion, employing the modified Delphi method. All statements were substantiated by the level of evidence and the strength of the recommendation. We created 27 consensus statements for WON diagnosis and management, including details of endoscopic procedures. When there was not enough solid evidence to support the statements, this was clearly acknowledged to facilitate future research. Proposed management strategies were formulated and are illustrated using flow charts. These recommendations, which are based on the best current scientific evidence and expert opinion, will be useful for guiding endoscopic management of WON. Part 1 of this statement focused on the epidemiology, diagnosis, and timing of intervention.