Showing papers in "Journal of Gastroenterology and Hepatology in 2015"

Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results.

Abstract: Abstact Background and Aim The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid-gut for refractory Crohn's disease (CD). Methods We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey–Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid-gut and assessed during follow-up. Results Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15-month follow-up. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD. Conclusion This is a pilot study with the largest sample of patients with refractory CD who underwent single FMT. The results demonstrated that FMT through mid-gut might be a safe, feasible, and efficient rescue therapy for refractory CD.

Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study.

Abstract: Background and Aim The biosimilar of infliximab, CT-P13, has recently been shown to be equivalent to infliximab in both efficacy and safety in the treatment of rheumatologic diseases. However, no data are available with respect to the drug's efficacy in patients with inflammatory bowel disease (IBD). We aimed to assess the efficacy and safety of CT-P13 in IBD patients Methods This was a retrospective multicenter study including both anti-tumor necrosis factor (TNF) naive patients and patients who switched from the biologic originator to CT-P13. Results In anti-TNF naive Crohn's disease (CD) patients (n = 32), clinical response and remission rates were 90.6% and 68.8% at week 2, 90.6% and 84.4% at week 8, 95.5% and 77.3% at week 30, and 87.5% and 75.0% at week 54, respectively. In anti-TNF naive ulcerative colitis (UC) patients (n = 42), clinical response and remission rates were 76.2% and 19.0% at week 2, 81.0% and 38.1% at week 8, 91.3% and 47.8% at week 30, and 100% and 50.0% at week 54, respectively, while mucosal healing rates were 58.3% at week 8, 66.7% at week 30, and 66.7% at week 54. The efficacy of CT-P13 was maintained in 92.6% (25/27) of CD patients and in 66.7% (6/9) of UC patients after switching from its originator. Adverse events related to CT-P13 occurred in 11.8% of UC patients. Conclusions CT-P13 appears to have comparable efficacy, safety, and interchangeability with its originator in the treatment of IBD. Further prospective studies with long-term follow-up periods will be needed to confirm the biosimilarity of CT-P13.

Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality.

Abstract: Background Bacterial translocation from the gut plays an important role in the pathophysiology of acute-on-chronic liver failure (ACLF). However, gut dysbiosis in ACLF was not widely documented in previous studies. Aim This research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness. Methods Fecal microbiota of 79 ACLF patients (42 patients were followed in the next 4 weeks after the first visit for longitudinal study) and 50 healthy controls was analyzed by 16S ribosomal DNA pyrosequencing. Results There was a marked difference between the ACLF group and the control group. The overall microbial diversity and richness were significantly lower in ACLF than in controls. ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. The relative abundance of Lachnospiraceae was obviously decreased in ACLF patients with hepatic encephalopathy. The gut microbiota kept relatively stable in a short term after the onset of ACLF. The use of antibiotics only showed moderate impacts on the gut microbiota. The relative abundance of Pasteurellaceae and Model of End Stage Liver Disease score were independent factors predicting mortality rate. Network analysis comparison showed robust correlations between specific bacterial families (Ruminococcaceae and Lachnospiraceae) and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor alpha, IL-2) in ACLF patients. Conclusions These data suggest gut dysbiosis in ACLF and its predictive value for mortality. The results thus open up the possibility of designing diagnostic biomarkers and targeted probiotics aimed at decreasing mortality in ACLF.

Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study

Abstract: Background and Aim: Crohn's disease pathogenesis involves alterations in the gut microbiota. We characterized the mucosa-associated microbiota at the time of surgical resection and 6 months later to identify bacterial profiles associated with recurrence and remission. Methods: Tissue samples were collected from surgical resection specimens in 12 Crohn's disease patients, and at 6 months postoperative colonoscopy from the neoterminal ileum and anastomosis. Endoscopic recurrence was assessed using the Rutgeerts score. Microbiota was characterized using microarray and 454 pyrosequencing. Longitudinal comparisons were made within patients, and cross-sectional comparisons made with colonoscopic biopsies from the terminal ileum and cecum of 10 healthy subjects. Results: Microbiota of healthy subjects had high diversity and was dominated by the Firmicutes, Bacteroidetes, and Proteobacteria phyla. Biodiversity was lower in Crohn's disease patients at the time of surgery, increased after surgery, but still differed from healthy subjects. Crohn's disease patients with recurrent disease retained a microbiota favoring proteolytic-fueled fermentation and lactic acid-producing bacteria, including Enterococcus and Veillonella spp., while those maintaining remission demonstrated predominant saccharolytic Bacteroides, Prevotella, and Parabacteroides spp., and saccharolytic, butyrate-producing Firmicutes. Conclusion: In Crohn's disease, the mucosa-associated microbiota diversity is reduced at the time of surgery, but also differs between patients with different clinical outcomes at 6 months. These findings may provide prognostic information at the time of surgery, allowing identification of patients at increased risk of recurrence, and provide basis for a more targeted approach for therapeutic interventions after surgery.

PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease.

Abstract: Background and aim Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients. Methods This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy. Results One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group. Conclusion Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.

Rising incidence of early-onset colorectal cancer in Australia over two decades: Report and review

Abstract: The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps.

Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm.

Abstract: Background and Aim Screening and early detection reduces mortality due to colorectal cancer (CRC). Methylated Septin 9 (SEPT9) is a new blood-based biomarker for CRC. We evaluated the performance of the second-generation SEPT9 assay for the detection of colorectal neoplasm, and compared it with fecal immunochemical test (FIT). Methods A total of 135 patients with CRC, 169 with adenomatous polyps, 81 with hyperplastic polyps, and 91 healthy controls were included. The clinical status of all subjects was verified by colonoscopy. In all patients, peripheral blood samples were taken for SEPT9 testing using Epi proColon 2.0 test. For 177 patients, both SEPT9 and FIT were performed. Results The sensitivity and specificity of SEPT9 for CRC were 74.8% (95% confidence interval [CI]: 67.0–81.6%) and 87.4% (vs non-CRC, 95% CI: 83.5–90.6%), respectively. SEPT9 was positive in 66.7% of stage I, 82.6% of stage II, 84.1% of stage III, and 100% of stage IV CRCs. The sensitivity of SEPT9 for advanced adenomas was 27.4% (95% CI: 18.7–37.6%). The sensitivity and specificity of FIT for CRC was 58.0% (95% CI: 46.1–69.2%) and 82.4% (95% CI: 74.4–88.7%), respectively. SEPT9 showed better performance in CRC detection than FIT, but similar among advanced adenomas. Conclusions With improved performance characteristics in detecting CRC, the second-generation SEPT9 assay could play an important role in CRC screening and early detection.

Malnutrition in cirrhosis increases morbidity and mortality

Abstract: Background and Aims Malnutrition is frequent in patients with cirrhosis and is associated with complications like ascites, hepatic encephalopathy, infections, and death We determined the prevalence of malnutrition by various methods and its clinical importance in patients with cirrhosis Methods Consecutive patients of cirrhosis from August 2013 to February 2015 were assessed Nutritional status was assessed by traditional model (mid-arm circumference, triceps skinfold thickness, serum albumin, creatinine height index, total lymphocyte count), handgrip, and body composition analysis measuring skeletal muscle mass and body fat mass All patients were followed up for 12 months to assess the outcome Results 247 patients (age 4210 ± 1014 years, 81% male) were included in the study Etiology of cirrhosis was alcohol in 53% patients Prevalence of malnutrition was 595% according to traditional model, 668% by body composition analysis and 714% by handgrip Nutritional status was poor in alcoholic cirrhotics versus nonalcoholics as assessed by triceps skinfold thickness (933 ± 29 vs 1164 ± 35 mm; P = 0001), serum albumin (251 ± 4 vs 281 ± 4 g/L; P = 0001), and body fat mass (76 ± 31 vs 87 ± 33 kg; P = 0008) Prevalence of malnutrition was 12/27 (445%), 96/131 (733%) and 84/89 (944%) in Child's class A, B, and C respectively Complications requiring hospitalization (713% vs 382%; 0002) and mortality (411% vs 182%; P = 0001) were more in malnourished patients compared to well nourished Nutritional assessment parameters significantly correlated with the liver disease severity (P < 005) Conclusions Prevalence of malnutrition is high in patients with cirrhosis It is associated with increased complications and mortality

Childhood adiposity trajectories and risk of nonalcoholic fatty liver disease in adolescents

Abstract: Background and Aims Nonalcoholic fatty liver disease (NAFLD) and its metabolic risk factors are recognized during childhood and adolescence. Identification of adolescents at risk of NAFLD from childhood anthropometry may expose opportunities to influence the hepatic and metabolic destinies of individuals. We sought associations between NAFLD diagnosed during adolescence and earlier life trajectories of anthropometry, in a population-based cohort of predominantly Caucasian adolescents. Methods Assessment for NAFLD, using questionnaires and liver ultrasound was performed on 1170 adolescents, aged 17 years, from the population-based Raine Cohort. We sought associations between NAFLD in adolescents and serial anthropometric measurements recorded from birth, childhood and adolescence. Results NAFLD was diagnosed in 15.2% of adolescents. Birth anthropometry, including birth weight, skinfold thickness and ponderal index, was not associated with NAFLD. However, adiposity differences between 17-year-old adolescents with NAFLD and those without NAFLD were apparent from age 3 years. Greater adiposity trajectories for weight, body mass index, skinfold thickness, mid-arm circumference and chest circumference from age 3 years onwards, particularly in males, were associated with the diagnosis of NAFLD and severity of hepatic steatosis at age 17 years (p<0•05). The strength of the associations increased with age after 3 years for each adiposity measure (all p<0•001). Conclusions Trajectories of childhood adiposity are associated with NAFLD. Adiposity attained by three years of age and older, but not at birth, was associated with the diagnosis and severity of hepatic steatosis in late adolescence. Exploration of clinically relevant risk factors and preventative measures for NAFLD should begin during childhood.

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Abstract: Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

New simple prognostic score for primary biliary cirrhosis: Albumin-bilirubin score.

Abstract: Background and Aim Serum albumin and bilirubin are the most significant independent prognostic factors to predict hepatic events in patients with primary biliary cirrhosis (PBC). We aimed to investigate the prognostic significance of a new prognostic score, the albumin-bilirubin (ALBI) score, among PBC patients. Methods In a retrospective longitudinal cohort of 61 Chinese PBC patients with follow-up period up to 18.3 years, the prognostic performance of the ALBI in prediction of hepatic events was compared with other well-established prognostic scores: Child–Pugh score, model of end-stage liver disease, Mayo risk score, Yale, European, and Newcastle models. Results Fifteen patients (24.6%) developed hepatic events during follow-up. The c-index (0.894) and χ2 by likelihood ratio test (36.34) of the ALBI score were highest in comparison to other models. The ALBI score was the only independent prognostic factor by multivariate analysis and its adjusted hazard ratio of developing hepatic event was 27.8 (P −2.60 to −1.39), and grade 3 (> −1.39) groups. The 2-, 5-, and 10-year event-free survivals for grade 1, grade 2, and grade 3 groups were 100.0% versus 100.0% versus 57.1%, 100.0% versus 88.5% versus 14.3%, and 100.0% versus 81.7% versus 0.0%, respectively (P < 0.001). Conclusion The ALBI score is readily derived from a blood test without using those factors evaluated subjectively or obtained by invasive procedures. It is an independent prognostic factor for PBC patients and provides better/similar prognostic performance compared with other prognostic scores.

Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study.

Abstract: Background and Aim Recent cross-sectional studies have been reported the possibility that light to moderate alcohol consumption might be negatively associated with fatty liver. However, there has been no large-scale longitudinal study addressing an impact of alcohol consumption on a development of fatty liver diagnosed by ultrasonography. Thus, we investigated the impact of alcohol consumption on a natural history of fatty liver. Methods We analyzed 5437 apparently healthy Japanese who received the health checkup programs repeatedly over 10 years. In this study, we used a standardized questionnaire for addressing the medical history and lifestyle and used a standardized ultrasonographic diagnosis for fatty liver. The total amount of alcohol consumed per week was calculated and classified into four grades; none or minimal, light, moderate, or heavy alcohol consumption ( 280 g/week, respectively). The hazard risks of alcohol consumption for the development of fatty liver were calculated by Cox hazard model after adjusting age, BMI, and parameters for lifestyle. Results During 10 years of follow-up, fatty liver was continuously diagnosed just in 10% of men and 20% of women with fatty liver at the baseline. In men, the adjusted hazard risks of light and moderate alcohol consumption for the development of fatty liver were 0.72 (95% confidence interval 0.60–0.86, P < 0.001) and 0.69 (0.57–0.84, P < 0.001), respectively. However, they were not significant in women. Conclusions The newly onset of fatty liver was significantly repressed in apparently healthy men who consume light to moderate alcohol.

Testosterone in men with advanced liver disease: abnormalities and implications.

Abstract: Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials.

Emerging leadership lecture: Inflammatory bowel disease in Asia: emergence of a "Western" disease.

Abstract: More than a decade ago, inflammatory bowel disease (IBD) is rare in Asia. Today, the importance of IBD in Asia is exemplified by its rapidly increasing incidence, complicated disease behavior, and substantial morbidity. In the first large-scale population-based epidemiologic study in Asia, the incidence of IBD varied from 0.60 to 3.44 per 100,000. There has been a twofold to threefold increase in the incidence of IBD in several countries in Asia. Ulcerative colitis (UC) is more prevalent than Crohn's disease (CD), although CD incidence is rapidly increasing. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. Complicated and penetrating CD are common in Asia. These epidemiologic changes may relate to increased contact with the West, westernization of diet, improved hygiene, increasing antibiotics use, or changes in the gut microbiota. Asian patients with CD have altered gut microbiota compared with their healthy counterparts and Caucasian CD subjects. Mucosa-associated microbiota in IBD may differ geographically. In a population-based case-control study, breast-feeding, having pets, and better sanitary conditions were protective of IBD, suggesting that childhood environment plays an important role in modulating disease development. Genetic factors also differ between Asians and Caucasians. Nucleotide oligomerization domain-2 (NOD2) and autophagy variants were not associated with CD, but tumor necrosis factor superfamily gene-15 polymorphisms were strongly associated with CD in East Asians. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.

Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection.

Abstract: Background and aim: Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR. Methods: The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index were calculated based on laboratory data at the time that SVR was documented (SVR24). Results: Patients continued follow-up visits for 1.0-22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at 5 years and 4.3% at 10 years. The use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. The presence of diabetes mellitus (risk ratio 2.08; P = 0.0451) and FIB-4 index calculated at the time of SVR24 (risk ratio 1.73; P = 0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis. Conclusions: Patients with diabetes mellitus and patients with the elevation of FIB-4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.

Gender disparity in chronic hepatitis B: Mechanisms of sex hormones.

Abstract: Hepatitis B virus (HBV) is a common human pathogen transmitted worldwide, and its chronic infection is a well-known risk factor for hepatocellular carcinoma (HCC). The sex disparity of HBV-related liver diseases has been noticed for a long time, which could be attributed to sex hormone effects, other than gender behaviors or environmental impact. This difference is experimentally confirmed in HBV transgenic mice, as well as in immunocompetent mice receiving hydrodynamic delivery of HBV. Androgen and estrogen pathways were identified to play opposite regulations of HBV transcription by targeting viral enhancer I at molecular level. In addition to the direct effects on HBV life cycle, sex hormones may be also involved in the immune response to HBV infection and the progression of associated liver diseases, although the detailed mechanisms are still unclear. Besides, several unaddressed issues such as HBV entry, microRNA profiles, viral integration, and adaptability in which androgen and estrogen axes might be involved are warranted to be delineated. The comprehensive understanding of the sex disparity in HBV virology and pathogenesis will be helpful to provide newly biomarkers for clinical diagnosis and develop novel drugs to manage HBV-related HCC patients.

Prospective population‐based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity

Abstract: Background and Aim We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. Methods Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. Results We report on the early outcomes (median 18 months, range 12–60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P < 0.05). Twenty-four percent of UC patients were hospitalized, most within the first 12 months. Intestinal resection rates were 13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates in UC were 2% and 13% at 1 and 5 years. High C-reactive protein (CRP) at diagnosis was associated with colectomy. Conclusions A high rate of inflammatory disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD and UC were identified. In CD, ileal involvement and complex disease behavior are associated with a more severe disease course, while in UC a high CRP predicted this outcome.

Feasibility and safety of a novel dedicated device for one-step EUS-guided biliary drainage: A randomized trial.

Abstract: Background and Aims EUS-guided biliary drainage (EUS-BD) has been proposed as an alternative for patients after failed ERCP. To date, the evaluation of dedicated device for one-step EUS-BD has been limited. To determine feasibility and safety of a newly designed 7F stent introducer with tapered metal tip as a push-type dilator for one-step metal stent placement without additional fistula dilation in EUS-BD. Methods Thirty-two patients with malignant biliary obstruction and failed ERCP were randomly assigned to a dedicated stent introducer with a modified hybrid metal stent (DH group, n = 16) or a conventional 8.5F biliary metal stent introducer with a fully covered metal stent (FC group, n = 16). The technical success, procedural times, clinical success rate, and adverse event rates were evaluated. Results One-step technical success without additional fistula dilation in the DH was 88% (14/16). Multi-step process in a stent placement was performed in all patients of the FC group. The procedural time in the DH was significantly shorter than the FC (10 vs. 15 min, P = 0.007). No difference in overall technical or clinical success was seen between the groups. The rate of an early adverse event was common in the FC compared with the DH (31.3% [5/16] in the FC vs. 6.3% [1/16] in the DH, P = 0.172), although not statistically significant. Conclusions A dedicated device for one-step EUS-BD may be technically feasible, safe, and shorten the procedural times with less chance of an additional fistula dilation process, resulting in a potential reduction of the early adverse events.

Inflammatory bowel disease pathogenesis: Where are we?

Abstract: Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An “IBD integrome” approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it.

Ipilimumab‐induced toxicities and the gastroenterologist

Abstract: Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1 mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.

Radiofrequency ablation versus laser ablation for the treatment of small hepatocellular carcinoma in cirrhosis: a randomized trial.

Abstract: Background and Aim In patients with cirrhosis and small hepatocellular carcinoma (HCC), thermal ablation is currently recognized as an effective local treatment. Among thermal procedures, radiofrequency ablation (RFA) is the most diffusely used and is the standard against which any new treatment should be compared. In retrospective studies, laser ablation (LA) resulted as safe and effective as RFA. Therefore, we performed a non-inferiority randomized trial comparing RFA with LA in patients with cirrhosis and HCC within Milan criteria. Methods Overall, 140 patients with 157 HCC nodules were randomly assigned to receive RFA or LA. The primary end-point was the proportion of complete tumor ablation (CTA). Secondary end-points were time to local progression (TTLP) and overall survival (OS). Results Per patient CTA rates after RFA and LA were 97.4% (95% CI, 91.0–99.3) and 95.7% (88.1–98.5), respectively (difference = 1.4%, 95% CI from −6.0% to + 9.0%). Per nodule CTA rates for RFA and LA were 97.4% (91.0–99.3) and 96.3% (89.6–98.7), respectively (difference = 1.1%, from −5.7% to + 8.1%). The mean TTLP was comparable between RFA group (42.0 months; 95% CI, 36.83–47.3) and LA group (46.7 months; 95% CI, 41.5–51.9) (P = .591). The mean OS was 42 months in both groups and survival probability at 1 and 3 years was 94% and 89% in RFA group, and 94% and 80% in LA group. Conclusion LA resulted not inferior to RFA in inducing the CTA of HCC nodules and therefore it should be considered as an evaluable alternative for thermal ablation of small HCC in cirrhotic patients.

Hepatitis B virus infection and metabolic syndrome: Fact or fiction?

Abstract: Although hepatitis C virus infection is known to be linked with insulin resistance, dyslipidemia, and hepatic steatosis, the relationship between hepatitis B virus (HBV) infection and metabolic factors remains unclear. HBV infection is a health problem worldwide, especially in endemic regions such as Asia and Africa. It induces liver decompensation, cirrhosis, hepatocellualr carcinoma, and premature mortality. The prevalence of metabolic syndrome continues to increase in parallel with the epidemic of obesity, which is closely associated with the development of diabetes, cardiovascular disease, or even cancer. The systemic review shows that chronic HBV infection protects against instead of promotes fatty liver. The mechanism is possibly due to a lower frequency of dyslipidemia profile in patients with chronic HBV infection. The association of HBV with metabolic syndrome, insulin resistance, and the risk of arteriosclerosis is still inconclusive. In addition, obesity, diabetes, and metabolic syndrome may accelerate the progression of liver disease in patients with chronic HBV infection and synergistically induce cirrhosis or even hepatocellualr carcinoma development.

Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients.

Abstract: Background and Aim The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. Methods A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). Results Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14–4.85], P = 0.02), hepatic complications (HR 2.04, [1.16–3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05–4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96–4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). Conclusion The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.

Incidence and survival in late liver metastases of colorectal cancer

Abstract: Background and Aims Data concerning the risk of long-term liver metastasis following surgery of colorectal cancer in the general population are scarce. The 10-year incidence and prognosis of metachronous liver metastases remain unknown. Methods Among 4584 patients resected for cure for colorectal cancer recorded in two French digestive population-based cancer registries between 1985 and 2000, 602 presented metastases including liver metastases. Results The cumulated incidence of liver metastasis was 15% at 5 years and 17% at 10 years, and was mainly related to stage at diagnosis. The 10-year cumulative incidence was 6% for stage I and 30% for stage III. The hazard ratio was 3.2 [2.4–4.3] for stage II and 6.9 [5.1–9.2] for stage III compared with stage I. Among survivors with no recurrence five years after diagnosis, 2.2% developed liver metastasis between 5 and 10 years. Resection for cure of liver metastases was performed in 35% of patients aged under 75 years and in 10% of patients over 75 (P < 0.001). After resection for cure, 10-year relative survival improved from 21% during the period 1985–1997 to 34% during the period 1998–2011 (P = 0.023). Survival in patients with liver metastasis diagnosed between six and 12 months after surgery was less than half that in patients with metastasis diagnosed later (HR: 0.6 [0.4–1.0]). Conclusion Liver metastases from colorectal cancer remain a substantial problem and continue to occur long after five years. This study furnishes unbiased figures that can be used as a reference. Liver metastases that appear late have a better prognosis.

Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.

Abstract: Background and Aim Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. Methods Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. Results Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor–host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. Conclusions Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor–host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.

A common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: A meta-analysis

Abstract: Background and Aim Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD. Methods We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined. Results This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14–1.36, P < 0.00001). Analysis also revealed significant associations with different alternative genetic models for the inheritance: dominant, recessive, and homozygote (OR 1.40, 95%CI 1.23–1.61, P < 0.00001; OR 0.79, 95% CI 0.68–0.91, P = 0.001, and; (OR 1.27, 95% CI 1.10–1.47, P = 0.001, respectively), but not the heterozygote model. Population subgroup analysis demonstrated similar effect size in both Asians and non-Asians (OR 1.27, 95%CI 1.12–1.45, P = 0.0003 and OR 1.22, 95%CI 1.10–1.37, P = 0.0003, respectively). Conclusions Our meta-analysis provides evidence of significant association between GCKR rs780094 and risk of NAFLD. Similar effect size was demonstrated in both Asian and non-Asian populations.

Diagnostic features of sessile serrated adenoma/polyps on magnifying narrow band imaging: a prospective study of diagnostic accuracy.

Abstract: Background and Aims The narrow band imaging classification system (NBI International Colorectal Endoscopic [NICE] classification) classifies colorectal polyps very accurately. However, sessile serrated adenoma/polyps (SSA/Ps) pathologically resembles hyperplastic polyp and has a possibility to be left in situ on NICE classification. The aim of this study was to establish and evaluate new simple diagnostic features for SSA/Ps using magnifying narrow band imaging (M-NBI). Methods We performed a single-arm observational study of diagnostic accuracy in two stages, as follows: seeking stage, development of simple diagnostic features for SSA/P and definition of diagnostic criteria based on retrospective assessments of M-NBI; and validation stage, prospective validation and evaluation of the new diagnostic criteria. Results In the seeking stage, we identified brownish, oval, expanded crypt openings and thick-branched vessels on the surfaces of SSA/Ps. We named these “expanded crypt openings” (ECOs) and “thick and branched vessels” (TBVs), respectively. In the validation stage, we enrolled 796 polyps in 261 patients, and classified 126 polyps as NICE type 1; all these lesions were endoscopically removed and assessed histopathologically. The sensitivity, specificity, and accuracy of ECOs for SSA/Ps were 84.3%, 81.1%, and 82.4%, whereas those of TBVs were 45.1%, 68.9%, and 59.2%, respectively. M-NBI provided a sensitivity of 98% and specificity of 59.5% for discrimination of SSA/Ps from other lesions classified as NICE type 1. Conclusions Identification of ECOs, supplemented with TBVs, has high sensitivity for the diagnosis of SSA/P. These findings may facilitate the use of endoscopic optical diagnosis in clinical practice.

Non-alcoholic fatty liver disease comorbid with major depressive disorder: The pathological features and poor therapeutic efficacy.

Abstract: Background and Aim Major depressive disorder (MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. Methods A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. Results There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. Conclusion This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal.

Long-term clinical outcome of patients with cirrhosis and refractory ascites treated with transjugular intrahepatic portosystemic shunt insertion.

Abstract: Background and Aim Transjugular intrahepatic portosystemic shunt (TIPS) is indicated for the treatment of refractory ascites in cirrhosis. The long-term outcome of TIPS for refractory ascites is unknown. The aim of this study is to describe the natural history of patients with refractory ascites post-TIPS, and compare between polytetrafluoroethylene (PTFE)-covered versus bare stents. Methods A retrospective chart review of patients who had TIPS for refractory ascites was conducted. Prospectively collected data include demographics, angiographic data, blood work, and urinary sodium excretion. Results There were 136 patients who received TIPS (bare = 104, covered = 32) for over 22 years. Patients with PTFE stents had lower international normalized ratio and model for end-stage liver disease score. More patients with bare stents developed shunt dysfunction (74.0% vs 24.1%, P < 0.0001) and required more TIPS revisions (1.6 ± 0.2/patient vs 0.2 ± 0.1, P < 0.0001). Urinary sodium excretion increased significantly from first month and progressed to 98 ± 9 mmol/day at 12th month post-TIPS (P < 0.001 vs baseline), concurrent with improved renal function. Most patients (77.6%) completely cleared the ascites without diuretics, but many achieved this beyond 2 years. Number of TIPS revision was predictive of complete response at 12 months (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5–0.9, P < 0.05). Age (hazard ratio [HR] = 1.05 [95% CI 1.02–1.08], P < 0.01), complete response (HR = 0.22 [95% CI 0.12–0.40], P < 0.0001) and polytetrafluoroethylene stents (HR = 0.23 [95% CI 0.05–0.97], P < 0.05) were predictive of survival. Conclusion TIPS is an effective treatment for cirrhotic refractory ascites. Ascites clearance is dependent on number of TIPS revision, whereas survival is predicted by younger age, complete response, and covered stent use, although era effect likely contributed to improved survival with covered stent use.

Chronic hepatitis C infection is associated with insulin resistance and lipid profiles

Abstract: Background and Aim Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. Methods We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. Results When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Conclusions Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.