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  • Multiple Cycles of Granulocyte Colony Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-21
    Arka De; Sunita Kumari; Akash Singh; Amritjyot Kaur; Rattiram Sharma; Ashish Bhalla; Navneet Sharma; Naveen Kalra; Virendra Singh

    Background & Aims There is controversy over inclusion of granulocyte colony stimulating factor (G-CSF) in treatment of decompensated cirrhosis. Previous studies tested only a single cycle of G-CSF administration or were underpowered to detect changes in survival time. We performed an adequately powered study to determine whether multiple cycles of G-CSF increase survival of patients 1 year after the start of therapy. Methods We conducted an open-label trial of 100 patients with decompensated cirrhosis without acute-on-chronic liver failure at a tertiary centre from July 2016 through June 2018. The patients were randomly assigned to a group given 5 days of G-CSF every 3 months, with standard medical therapy, in 4 cycles (group A, n=50) or standard medical therapy alone (group B, n=50). The primary outcome was survival for 12 months after treatment began. Secondary outcomes were increase in number of CD34+ cells at day 6 compared with day 0, along with reductions in Child Turcotte Pugh and model for end-stage liver disease scores, increased control of ascites, reduced decompensation and episodes of infection, fewer hospitalizations, lower liver stiffness measurements, increased quality of life and nutrition, fulfilment of liver transplant criteria, and fewer adverse events at 12 months after the start of treatment. Results Groups A and B were comparable at baseline. Survival at 12 months after initiation of treatment was significantly higher in group A (74%) than group B (42%) (P<.001). Blood samples from patients in group A had significantly more CD34+ cells on day 6 than on day 0 (P<.001); there was no significant change in group B. Compared with patients in group B, patients in group A had significant reductions in Child Turcotte Pugh and model for end-stage liver disease scores, increased ascites control, fewer infections and hospitalizations, lower liver stiffness measurements, an increased quality of life, and a lower number fulfilled the liver transplant criteria (P<.05). There was no improvement in nutrition in either group, compared with baseline. G-CSF was safe and well tolerated. Conclusions Administration of multiple cycles of G-CSF increases numbers of hematopoietic stem cells and survival of patients with decompensated cirrhosis receiving standard medical treatment. Addition of G-CSF to medical treatment might provide a bridge to liver transplantation for these patients. ClincialTrials.gov no: NCT03415698

    更新日期:2020-02-21
  • Differences in Incidence and Mortality Trends of Colorectal Cancer, Worldwide, Based on Sex, Age, and Anatomic Location
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-21
    Martin CS. Wong; Junjie Huang; Veeleah Lok; Jingxuan Wang; Franklin Fung; Hanyue Ding; Zhi-Jie Zheng

    Background & Aims We studied incidence and mortality trends of colorectal cancer (CRC) in 39 countries according to age, sex, and anatomical location (colon vs rectum). Methods We retrieved incidence data from registries from 36 countries. The registries included: Cancer Incidence in 5 Continents (CI5) volumes I–XI; the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute; and the Nordic Cancer Registries from Europe. We obtained mortality data from 39 countries of the World Health Organization database. We evaluated average annual percent changes in CRC incidence and mortality in the past decade using joinpoint regression analysis. Results From 2007 to 2016, 2006 to 2015, or 2005 to 2014, depending on the availability of the data, the incidence of colon cancer increased in 10 of 36 countries analyzed (all in Asia or Europe); India had the greatest increase, followed by Poland. All 10 of these countries have medium–high Human Development Index (HDI) scores. Six countries had a decrease in colon cancer incidence; these countries had the highest HDI scores; the United States (US) had the greatest decrease, followed by Israel. Seven countries (including all countries from Northern America) had a decrease in incidence among persons older than 50 y. Eight countries had an increase in colon cancer incidence among persons younger than 50 y, including the United Kingdom and India. Countries with a decreased or stable incidence among persons 50 y or older but a significant increase in persons younger than 50 y included Germany, Australia, the US, Sweden, Canada, and the United Kingdom. Only Italy had a decrease in CRC incidence among persons younger than 50 y. Among women, 12 of 36 countries (all from Asia and Europe) had an increase in colon cancer incidence and 7 countries had a decrease; India had the greatest increase followed by Slovenia. Five of 36 countries had an increase in incidence of rectal cancer and 8 countries had a decrease; Ecuador and Thailand had the greatest increases in incidence. The incidence of rectal cancer among persons younger than 50 y increased significantly in Finland, Australia, Canada, the US, and Netherlands. Four countries had an increase in incidence of rectal cancer in women; Ecuador had the greatest increase followed by Thailand. Incidence of rectal cancer in women decreased in 8 countries. Among women younger than 50 y, rectal cancer incidence increased, despite a decrease in women older than 50 y, in Costa Rica, Slovenia, Japan, Slovakia, Canada and the US had an increase in incidence although their elder population had a stable or decreased incidence. Twenty-four countries reported a reduction in CRC mortality, including the North America, Oceania, and most European countries. Nevertheless, some countries from Asia, Latin America, and Southern Europe had significant increases in CRC mortality. Conclusions In an analysis of incidence and mortality databases from 39 countries, we found that the incidence of colon and rectal cancers has continued to increase in countries with medium–high HDI and in younger populations. Preventive strategies are needed for countries with increasing CRC and rectal cancer incidence and mortality.

    更新日期:2020-02-21
  • Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients with Bile Acid Diarrhea in a Randomized Trial
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-21
    Priya Vijayvargiya; Michael Camilleri; Paula Carlson; Asha Nair; Sara Linker Nord; Michael Ryks; Deborah Rhoten; Duane Burton; Irene Busciglio; Alan Lueke; W. Scott Harmsen; Leslie J. Donato

    Background & Aims Approximately one-third of patients with IBS-diarrhea (IBS-D) have increased bile acid (BA) synthesis or excretion. An open-label study showed benefits of colesevelam on bowel functions, consistent with luminal BA sequestration by colesevelam. We compared the effects of colesevelam vs placebo on symptoms and gene expression patterns in the sigmoid colon mucosa in patients with BA diarrhea associated with IBS-D. Methods We performed a double-blind, parallel-group study of 30 adults with IBS-D and evidence of increased BA synthesis or fecal excretion, from December 2017 through December 2018 at a single center. Patients were randomly assigned (1:1) to groups given colesevelam (3 tablets, 625 mg each) or matching placebo, orally twice daily for 4 weeks. Stool diaries documented bowel functions for 8 days before and 28 days during colesevelam or placebo. Stool and fasting serum samples were collected for analyses of fecal BAs and serum levels of C4 and FGF19. We measured colonic transit by scintigraphy, mucosal permeability by in vivo excretion of saccharide probes, and mRNA levels in rectosigmoid biopsies. All measurements were made at baseline and on the last days of treatment. The primary endpoints were change in total fecal BA concentration and stool consistency. Results Compared with placebo, colesevelam was associated with significant changes in sequestered fecal total BA excretion (P<.001) and serum levels of C4 and FGF19 (both P<.001), and with a mean increase in fecal level of deoxycholic acid (10%; P=.07) compared to placebo. Colesevelam decreased colon mucosal expression of NR1H4 and P2RY4 and increased expression of GPBAR1, compared with baseline. Stool frequency and consistency, colonic transit, and permeability did not differ significantly between groups. Colesevelam was well tolerated. Conclusions In a randomized trial, we found that colesevelam increases delivery of total and secondary BAs to stool, hepatic BA synthesis, and colonic mucosal expression of genes that regulate BA, farnesoid X, and GPBAR1 receptors. Larger studies are needed to determine the effects on clinical responses. ClinicalTrials.gov no: NCT03270085

    更新日期:2020-02-21
  • Burden of Gastric Cancer
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-27
    Aaron P. Thrift; Hashem B. El-Serag

    Gastric cancer is a global health problem, with more than 1 million people newly diagnosed with gastric cancer worldwide each year. Despite its worldwide decline in incidence and mortality over the past 5 decades, gastric cancer remains the third leading cause of cancer-related death. Knowledge of global as well as regional epidemiology and risk factors for gastric cancer is essential for the practicing gastroenterologist to make personalized decisions about risk stratification, screening, and prevention. In this article, we review the epidemiology of gastric cancer as well as screening and prevention efforts to reduce global morbidity and mortality from gastric cancer. First, we discuss the descriptive epidemiology of gastric cancer, including its incidence, mortality, survival, and secular trends. We combine a synthesis of published studies with an analysis of data from the International Agency for Research on Cancer GLOBOCAN project to describe the global burden of gastric cancer and data from the US Cancer Statistics registry to discuss the change in incidence of gastric cancer in the United States. Next, we summarize current knowledge of risk factors for gastric cancer. Finally, we discuss prevention strategies and screening efforts for gastric cancer.

    更新日期:2020-02-20
  • Global Prevalence of Colorectal Neoplasia: A Systematic Review and Meta-Analysis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-16
    Martin C.S. Wong; Junjie Huang; Jason L.W. Huang; Tiffany W.Y. Pang; Peter Choi; Jingxuan Wang; Jason I. Chiang; Johnny Yu Jiang

    Background & Aims Most colorectal cancers (CRC) arise from colorectal adenomas, yet there is not enough information on global prevalence to inform health care policy. We examined the prevalence of any type of adenomas, advanced adenomas (AADs), and CRC according to age, sex, ethnicity, geographic regions, and anatomic location (proximal vs distal). Methods MEDLINE and Embase were searched from their inception through May 1, 2018, to identify population-based, observational studies that reported the prevalence of colorectal neoplasia. Studies on participants 15 years or older, with a sample size of 500 persons or more, were included. Metaprop (College Station, TX) was used to model within-study variability by binomial distribution and Freeman–Tukey Double Arcsine Transformation to stabilize the variances. The prevalence figures were presented by proportions and their 95% CIs using random-effects models. Results Our meta-analysis included 70 studies involving 637,414 individuals. The overall prevalence rates of adenoma (23.9%; 95% CI, 22.2%–25.8%), AAD (4.6%; 95% CI, 3.8%–5.5%), and CRC (0.4%, 95% CI, 0.3%–0.5%) were calculated. Subgroup analysis indicated that prevalence values (adenomas, AADs, and CRCs) were higher among men (29.7%, 6.5%, and 0.8%, respectively) than women (19.3%, 3.8% and 0.4%, respectively), among older adults (25.9%, 5.2%, and 0.6%, respectively) than younger adults (14.6%, 1.6%, and 0.1%, respectively), among Caucasians (23.7%, 6.6%, and 0.5%, respectively) than other ethnicities, in European countries (25.9%, 8.4%, and 0.8%, respectively) than other countries, and among patients with proximal (25.9%, 5.3%, and 0.1%, respectively) vs distal neoplasia. Conclusions In a systematic review and meta-analysis, we found a high prevalence of colorectal neoplasia among some populations. This indicates a need to expand CRC screening programs for these groups. The pooled prevalence estimates can be used as quality indicators for established CRC screening programs.

    更新日期:2020-02-20
  • Rate, Risk Factors, and Outcomes of Nonadherence in Pediatric Patients With Celiac Disease: A Systematic Review
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-04
    Anna Myléus; Norelle R. Reilly; Peter H.R. Green

    Background and aims The only treatment for celiac disease is strict adherence to a gluten-free diet (GFD). We performed a systematic review to investigate the rate of adherence to a GFD in children with celiac disease, risk factors that affect adherence, and outcomes of non-adherence. Methods We searched PubMed, Cochrane Library, EBSCO, and Scopus for studies through January 2019. We included observational studies of ≥50 children diagnosed with celiac disease and recommended for placement on a GFD. We collected data on adherence assessment (self-report, serology tests, structured dietary interview, biopsies, or assays for gluten immunogenic peptides), risk factors, and outcomes related to adherence. Findings were presented with medians, range, and a narrative synthesis. Results We identified 703 studies; of these, 167 were eligible for full-text assessment and 49 were included in the final analysis, comprising 7850 children. Rates of adherence to a GFD ranged from 23% to 98%. Comparable rates (median rates of adherence, 75%–87%) were found irrespective of how assessments were performed. Adolescents were at risk of non-adherence and children whose parents had good knowledge about celiac disease adhered more strictly. Non-adherence associated with patient growth, symptoms, and quality of life. Conclusion In a systematic review of 49 studies of children with celiac disease, we found substantial variation in adherence to a GFD among patients. Rate of adherence was not associated with method of adherence measurement, so all methods appear to be useful, with lack of consensus on the ideal metric. Studies are needed to determine the best method to ensure adherence and effects on long-term health.

    更新日期:2020-02-20
  • Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-18
    Xiaocen Zhang; Erin K. Ly; Sagarika Nithyanand; Rani J. Modayil; Dmitriy O. Khodorskiy; Sivaram Neppala; Sriya Bhumi; Matthew DeMaria; Jessica L. Widmer; David M. Friedel; James H. Grendell; Stavros N. Stavropoulos

    Background & Aims Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. Methods We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. Results Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. Conclusions In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

    更新日期:2020-02-20
  • Best Practices in Teaching Endoscopy Based on a Delphi Survey of Gastroenterology Program Directors and Experts in Endoscopy Education
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-21
    Navin L. Kumar; Benjamin N. Smith; Linda S. Lee; Justin L. Sewell

    Background and Aims Teaching endoscopy is a key objective of gastroenterology (GI) fellowship programs but the best approach is not known. We sought to characterize which teaching competencies experts considered most critical for endoscopy education. Methods We developed and refined 18 endoscopy teaching competencies based on literature review, personal experience, and interviews with experts. We invited GI fellowship program directors and endoscopy education experts to participate in a Delphi process to rate each proposed competency as essential, important but not essential, or not important using a 70% agreement threshold for consensus. Thirty-four GI fellowship program directors and 2 experts in endoscopy education participated (n = 36). Results Most survey participants were male (61.8%), associate professors (55.9%), and had performed at least a quarter of procedures with fellows (80.6%). Survey response rates were 94% (34 of 36) for round 1 and 91% (31 of 34) for round 2 (overall 31 of 36; 86.1%). After 2 rounds we achieved the predefined consensus level for most competencies. Fourteen of 18 competencies (77.8%) reached consensus after round 2: 10 (55.6%) were deemed essential and 4 (22.2%) were deemed important but not essential. Essential competencies included the following: discusses patient history and plans for procedure with trainee (100%), assumes control of procedure when trainee is unable to progress or if patient safety concerns arise (100%), maintains attention throughout the case (96.8%), and discusses the next steps in management for the patient (96.8%). Conclusions In a national Delphi survey of endoscopy education experts, we identified 10 essential endoscopy teaching competencies. These can be used to frame faculty development and standardize GI fellowship programs to promote high-quality endoscopy education.

    更新日期:2020-02-20
  • Mean Nocturnal Baseline Impedance Correlates With Symptom Outcome When Acid Exposure Time Is Inconclusive on Esophageal Reflux Monitoring
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-01
    Arvind Rengarajan; Edoardo Savarino; Marco Della Coletta; Matteo Ghisa; Amit Patel; C. Prakash Gyawali

    Background & Aims Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results. Methods We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic, >6%; physiologic, <4%; borderline or inconclusive, 4%–6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal, <2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients’ answers on standardized visual analog scales. Results Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P < .0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P = .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P < .0001 for each comparison). Conclusions When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy.

    更新日期:2020-02-20
  • Increased Prevalence of Celiac Disease in School-age Children in Italy
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-17
    Simona Gatti; Elena Lionetti; Linda Balanzoni; Anil K. Verma; Tiziana Galeazzi; Rosaria Gesuita; Novella Scattolo; Mauro Cinquetti; Alessio Fasano; Carlo Catassi

    Background & Aims Celiac disease is one of the most common diseases worldwide, with an apparent trend of increasing prevalence. We investigated the prevalence of celiac disease in children in Italy in 2015–2016 and compared that with data from 25 years ago. Methods We screened 4570 children (5–11 years old, 80.1% of the eligible population) from metropolitan areas of Ancona and Verona for HLA genes associated with increased risk of celiac disease, and for total serum levels of IgA and IgA class anti-tissue transglutaminase in HLA positives. Diagnoses of celiac disease were confirmed by detection of anti-endomysial antibody and analysis of intestinal biopsies. The prevalence of celiac autoimmunity and celiac disease were calculated and compared with values from the same geographical area during the years 1993–1995, after adjustment for the different diagnostic algorithm. Results We identified 1960 children with celiac disease-associated haplotypes (43% of children screened; 95% CI, 40.8%–45.2%). The prevalence of celiac disease autoimmunity in the HLA-positive subjects was 96/1706 (5.62%; 95% CI, 4.53%–6.71%) and 54 of these children satisfied the diagnostic criteria for celiac disease. In the eligible population there were other 23 known cases of celiac disease. The overall estimated prevalence of celiac disease was 1.58% (95% CI, 1.26%–1.90%); this value is significantly higher than the 1993–1995 adjusted prevalence (0.88%; 95% CI, 0.74%–1.02%). Conclusions We found the prevalence of celiac disease in children in Italy to be greater than 1.5%; this value has increased significantly over the past 25 years. Studies are needed to determine the causes of this large increase.

    更新日期:2020-02-20
  • Association Between Vulvovaginal Discomfort and Activity of Inflammatory Bowel Diseases
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-18
    Samsiya Ona; Kaitlyn James; Ashwin N. Ananthakrishnan; Millie D. Long; Christopher Martin; Wenli Chen; Caroline M. Mitchell

    Background & Aims Inflammatory bowel diseases (IBD) affect 200–400 people per 100,000 in the United States, about half of whom are women. We aimed to define the prevalence of vulvovaginal symptoms and association with IBD activity in a large cohort of women. Methods Women more than 18 years old with IBD (1250) completed an online survey querying the presence and severity of vulvar or vaginal itch, burn, or irritation, vaginal discharge or dryness, and vulvovaginal pain. The survey collected information on demographic features and IBD activity (categorized using the Manitoba index). Women with and without symptoms were compared using bivariate analyses. Logistic regression evaluated associations between IBD severity and vulvovaginal symptoms, adjusted for diagnosis, menopause, smoking, depression, and use of medications to treat IBD. Results A total of 512 (41%) women reported at least 1 moderate–severe vulvovaginal symptom. All vulvovaginal symptoms except vaginal dryness were more common in women with active IBD. In a multivariate model controlled for menopause, smoking, t-score from the PROMIS depression instrument, and use of IBD medications, women with constant or frequent active IBD, based on Manitoba index scores, had increased odds for moderate–severe vulvovaginal symptoms (odds ratio, 1.68; 95% CI, 1.22–2.32) compared to women in remission. Vulvovaginal discomfort frequently or always decreased interest in sex (n=336; 28%) or ability to have sex (n=207; 16%). Conclusions In an online survey of 1250 women, we found that women with more active IBD have increased prevalence of vulvovaginal discomfort, compared to women in remission. These symptoms affect sexual health.

    更新日期:2020-02-20
  • Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-04-19
    Maribeth R. Nicholson; Paul D. Mitchell; Erin Alexander; Sonia Ballal; Mark Bartlett; Penny Becker; Zev Davidovics; Michael Docktor; Michael Dole; Grace Felix; Jonathan Gisser; Suchitra K. Hourigan; M. Kyle Jensen; Jess L. Kaplan; Judith Kelsen; Melissa Kennedy; Sahil Khanna; Elizabeth Knackstedt; Stacy A. Kahn

    Background & Aims Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. Methods We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. Results Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. Conclusions Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.

    更新日期:2020-02-20
  • Efficacy of Tumor Necrosis Factor Antagonist Treatment in Patients With Refractory Ulcerative Proctitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-13
    Guillaume Pineton de Chambrun; Aurélien Amiot; Guillaume Bouguen; Stéphanie Viennot; Romain Altwegg; Edouard Louis; Michael Collins; Mathurin Fumery; Florian Poullenot; Laura Armengol; Anthony Buisson; Vered Abitbol; David Laharie; Philippe Seksik; Stéphane Nancey; Pierre Blanc; Yoram Bouhnik; Benjamin Pariente; Natalie Funakoshi

    Background & Aims It is a challenge to manage patients with ulcerative proctitis (UP) refractory to standard therapy. We investigated the effectiveness of tumor necrosis factor (TNF) antagonists in a large cohort of patients with refractory UP. Methods We conducted a nationwide retrospective cohort study of 104 consecutive patients with active UP refractory to conventional therapies, treated at 1 of 15 centers in France or 1 center in Belgium (the GETAID cohort). Patients received at least 1 injection of anti-TNF (infliximab, adalimumab, golimumab) from October 2006 through February 2017. Clinical response was defined as significant improvement in UC-related symptoms, and remission as complete disappearance of UC-related symptoms, each determined by treating physicians. We collected demographic, clinical, and treatment data. The median duration of follow-up was 24 months (interquartile range, 13–51 months). The primary outcome was clinical response of UP to anti-TNF treatment. Results Overall, 80 patients (77%) had a clinical response to anti-TNF therapy and 52 patients (50%) achieved clinical remission. Extra-intestinal manifestations (odds ratio OR, 0.24; 95% CI, 0.08–0.7), ongoing treatment with topical steroids (OR, 0.14; 95% CI, 0.03–0.73), and ongoing treatment with topical 5-aminosalycilates (OR, 0.21; 95% CI, 0.07–0.62) were significantly associated with the absence of clinical remission. Sixty percent (38/63) of the patients who had endoscopic assessment during follow up had mucosal healing. Among the overall population (n = 104), the cumulative probabilities of sustained clinical remission were 87.6% ± 3.4% at 1 year and 74.7% ± 4.8% at 2 years. Conclusions In a retrospective study of 104 patients with refractory UP, anti-TNF therapy induced clinical remission in 50% and mucosal healing in 60%. About two thirds of the patients were still receiving anti-TNF therapy at 2 years.

    更新日期:2020-02-20
  • Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-22
    Guillaume Bouguen; Audrey Huguet; Aurélien Amiot; Stéphanie Viennot; Franck Cholet; Maria Nachury; Mathurin Flamant; Jean-Marie Reimund; Véronique Desfourneaux; Arnaud Boureille; Laurent Siproudhis

    Background & Aims Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn’s disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. Methods We performed a retrospective study of data collected from the Groupe d’Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan–Meier method was used for statistical analysis. Results After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. Conclusions In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

    更新日期:2020-02-20
  • Monitoring a Combination of Calprotectin and Infliximab Identifies Patients With Mucosal Healing of Crohn’s Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-22
    Erwin Dreesen; Filip Baert; David Laharie; Peter Bossuyt; Yoram Bouhnik; Anthony Buisson; Guy Lambrecht; Edouard Louis; Bas Oldenburg; Benjamin Pariente; Marieke Pierik; C. Janneke van der Woude; Geert D’Haens; Séverine Vermeire; Ann Gils

    Background & Aims In the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn’s disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy. Methods We performed a post hoc analysis of patients with CD included in a trial to test the effects of infliximab dose escalation, based on biomarkers and serum concentrations of infliximab, on symptoms (the Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease trial; n = 122). We analyzed data from this study to determine whether concentrations of biomarkers and serum concentrations of infliximab were associated with endoscopic outcomes (n = 116). The primary end points were endoscopic response (CD endoscopic index of severity decrease ≥50% from baseline), endoscopic remission (CD endoscopic index of severity, <3), and absence of ulcers at weeks 12 and 54 of infliximab treatment. Results Infliximab trough concentrations greater than 23.1 mg/L at week 2 and greater than 10.0 mg/L at week 6 were associated with endoscopic remission at week 12 (positive predictive values, 72% and 76%; negative predictive values, 65% and 59%, respectively). During maintenance therapy, we found evidence for an exposure–response relationship only after dose escalation; trough concentrations greater than 10.6 mg/L were associated with the absence of ulcers at week 54 (positive predictive value, 49%; negative predictive value, 92%). Low fecal concentrations of calprotectin during therapy were associated with endoscopic response and remission (P < .05). Dose escalations increased trough concentrations of infliximab; persistent increase in fecal concentration of calprotectin, despite dose escalation, was associated with a lack of endoscopic response and remission. A significantly higher proportion of patients with antibodies to infliximab, identified by a drug-tolerant assay, dropped out of the study compared with patients without antibodies (P < .0001). Conclusions In a post hoc analysis of data from a trial to test the effects of infliximab dose escalation on symptoms, we found that during maintenance therapy, the combination of fecal concentration of calprotectin and trough concentration of infliximab can guide dose adjustment and increase the chances for endoscopic response and remission. ClinicalTrialsRegister.eu EudraCT no: 2011-003038-14.

    更新日期:2020-02-20
  • Lower Abnormal Fecal Immunochemical Test Cut-Off Values Improve Detection of Colorectal Cancer in System-Level Screens
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-11
    Emily Berry; Stacie Miller; Mark Koch; Bijal Balasubramanian; Keith Argenbright; Samir Gupta

    Background & Aims Noninvasive tests used in colorectal cancer screening, such as the fecal immunochemical test (FIT), are more acceptable but detect neoplasias with lower levels of sensitivity than colonoscopy. We investigated whether lowering the cut-off concentration of hemoglobin for designation as an abnormal FIT result increased the detection of advanced neoplasia in a mailed outreach program. Methods We performed a prospective study of 17,017 uninsured patients, age 50 to 64 years, who were not current with screening and enrolled in a safety-net system in Texas. We reduced the cut-off value for an abnormal FIT result from 20 or more to 10 or more μg hemoglobin/g feces a priori. All patients with abnormal FIT results were offered no-cost diagnostic colonoscopy. We compared proportions of patients with abnormal FIT results and neoplasia yield for standard vs lower cut-off values, as well as absolute hemoglobin concentration distribution among 5838 persons who completed the FIT. Our primary aim was to determine the effects of implementing a lower hemoglobin concentration cut-off value on colonoscopy demand and yield, specifically colorectal cancer (CRC) and advanced neoplasia detection, compared with the standard, higher, hemoglobin concentration cut-off value. Results The proportions of patients with abnormal FIT results were 12.3% at the 10 or more μg hemoglobin/g feces and 6.6% at the standard 20 or more μg hemoglobin/g feces cut-off value (P = .0013). Detection rates for the lower vs the standard threshold were 10.2% vs 12.7% for advanced neoplasia (P = .12) and 0.9% vs 1.2% for CRC (P = .718). The positive predictive values were 18.9% for the lower threshold vs 24.4% for the standard threshold for advanced neoplasia (P = .053), and 1.7% vs 2.4% for CRC (P = .659). The number needed to screen to detect 1 case with advanced neoplasia was 45 at the lower threshold compared with 58 at the standard threshold; the number needed to scope to detect 1 case with advanced neoplasia increased from 4 to 5. Most patients with CRC (72.7%) or advanced adenoma (67.3%) had hemoglobin concentrations of 20 or more μg/g feces. In the group with 10 to 19 μg hemoglobin/g feces, there were 3 patients with CRC (3 of 11; 27.3%) and 36 with advanced adenoma (36 of 110; 32.7%) who would not have been detected at the standard positive threshold (advanced neoplasia Pcomparison < .001). The proportion of patients found to have no neoplasia after an abnormal FIT result (false positives) was not significantly higher with the lower cut-off value (44.4%) than the standard cut-off value (39.1%) (P = .1103). Conclusions In a prospective study of 17,017 uninsured patients, we found that reducing the abnormal FIT result cut-off value (to ≥10 μg hemoglobin/g feces) might increase detection of advanced neoplasia, but doubled the proportion of patients requiring a diagnostic colonoscopy. If colonoscopy capacity permits, health systems that use quantitative FITs should consider lowering the abnormal cut-off value to optimize CRC detection and prevention. (ClinicalTrials.gov no: NCT01946282.)

    更新日期:2020-02-20
  • Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-25
    Elom K. Aglago; Inge Huybrechts; Neil Murphy; Corinne Casagrande; Genevieve Nicolas; Tobias Pischon; Veronika Fedirko; Gianluca Severi; Marie-Christine Boutron-Ruault; Agnès Fournier; Verena Katzke; Tilman Kühn; Anja Olsen; Anne Tjønneland; Christina C. Dahm; Kim Overvad; Cristina Lasheras; Antonio Agudo; Marc J. Gunter

    Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

    更新日期:2020-02-20
  • Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-16
    Shounak Majumder; Massimo Raimondo; William R. Taylor; Tracy C. Yab; Calise K. Berger; Brian A. Dukek; Xiaoming Cao; Patrick H. Foote; Chung Wah Wu; Mary E. Devens; Douglas W. Mahoney; Thomas C. Smyrk; Rahul Pannala; Suresh T. Chari; Santhi Swaroop Vege; Mark D. Topazian; Bret T. Petersen; Michael J. Levy; David A. Ahlquist

    Background & Aims Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). Methods We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. Results We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83–0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%–93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%–95%). Conclusions We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.

    更新日期:2020-02-20
  • Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-25
    Seung Up Kim; Yeon Seok Seo; Han Ah Lee; Mi Na Kim; Eun Hwa Kim; Ha Yan Kim; Yu Rim Lee; Hye Won Lee; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Kwang-Hyub Han; Seong Gyu Hwang; Kyu Sung Rim; Soon Ho Um; Won Young Tak; Young Oh Kweon; Beom Kyung Kim; Soo Young Park

    Background & Aims Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort. Methods We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis. Results Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8–13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement. Conclusions We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection.

    更新日期:2020-02-20
  • Durability of Spontaneous and Treatment-Related Loss of Hepatitis B s Antigen
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-16
    Ahmad Samer Alawad; Sungyoung Auh; Daniel Suarez; Marc G. Ghany

    Background & Aims Clearance of hepatitis B surface antigen (HBsAg) from serum is the most desirable end point and a proposed definition of functional cure for hepatitis B virus (HBV) infection. However, little is known about the long-term durability of HBsAg loss, and there is controversy over whether the development of antibodies against HBsAg (anti-HBs) is required for maintenance. We aimed to assess the durability of spontaneous or treatment-related (interferon or nucleos(t)ide analogue [NA]) loss of HBsAg. Methods We performed a retrospective study of patients with chronic HBV infection followed up at the National Institutes of Health from February 1980 through November 2017. We identified those with HBsAg loss, confirmed on 2 visits at least 24 weeks apart. Patients with hepatitis C virus, hepatitis D virus, human immunodeficiency virus, or human T lymphocyte virus co-infection or HBsAg loss after liver transplantation were excluded. Patients were assigned to the following groups: spontaneous clearance (cleared HBsAg without ever receiving treatment or those who received treatment with a NA or interferon and discontinued therapy >5 years before HBsAg loss), interferon-treated (cleared HBsAg either during treatment or ≤5 years after stopping interferon), and NA-treated (cleared HBsAg either during treatment or ≤5 years after stopping NA). Results Among the 787 HBsAg-positive patients, 89 achieved HBsAg loss; 65 of 89 had confirmed HBsAg loss, which was spontaneous in 19 of the patients (29%), after interferon in 22 (34%), and after NA in 24 (37%). Of the 65 patients with confirmed loss of HBsAg, 62 patients (95%) remained HBsAg negative after a mean time of 9.6 years from the first negative HBsAg test result. HBsAg seroreversion occurred in 3 of the 46 treated patients (7%) (1 interferon and 2 NA), 1 of whom was positive for anti-HBs. At the time of HBsAg loss, 33 of 65 (51%) were anti-HBs positive. At the last follow-up evaluation, anti-HBs was detectable in 50 of the 62 patients (81%) assessed. The rate of development of anti-HBs was proportionally higher among interferon-treated patients (19 of 21; 90%) than NA-treated patients (17 of 22; 77%) or patients with spontaneous loss of HBsAg (14 of 19; 74%). Conclusions In a retrospective study of 787 HBsAg-positive patients, loss of HBsAg (either spontaneous or after treatment) was confirmed in 8% and was durable. Seroconversion to anti-HBs increased over time and appeared to be more frequent after interferon treatment. HBsAg loss is therefore a robust end point for functional cure.

    更新日期:2020-02-20
  • Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-25
    Preya Janubhai Patel; Johnson Chieh-Yu Cheng; Xuan Banh; Lucy Gracen; Daniel Radford-Smith; Fabrina Hossain; Leigh Ula Horsfall; Kelly Lee Hayward; Suzanne Williams; Tracey Johnson; Nigel Neil Brown; Nivene Saad; Katherine Anne Stuart; Anthony William Russell; Patricia Casarolli Valery; Andrew Donald Clouston; Katharine Margaret Irvine; Anne Bernard; Elizabeth Ellen Powell

    Background & Aims There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF). Methods We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater. Results Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log10 FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52–0.59). The rate of increase in NFS and log10 FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log10 FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively. Conclusions Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.

    更新日期:2020-02-20
  • Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-27
    Rong Fan; Bin Zhou; Min Xu; Deming Tan; Junqi Niu; Hao Wang; Hong Ren; Xinyue Chen; Maorong Wang; Qin Ning; Guangfeng Shi; Jifang Sheng; Hong Tang; Xuefan Bai; Shi Liu; Fengmin Lu; Jie Peng; Jian Sun; Xiaoguang Dou

    Background & Aims There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. Methods We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. Results After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) Conclusions In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

    更新日期:2020-02-20
  • Diagnostic Accuracy of Non-Invasive Tests to Detect Advanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-19
    Christopher J. Schmoyer; Dhiren Kumar; Gaurav Gupta; Richard K. Sterling

    Background & Aims For patients with liver disease from hepatitis C virus (HCV) infection complicated by end-stage renal disease (ESRD), it is important to assess liver fibrosis before kidney transplantation. We evaluated the accuracy of non-invasive tests to identify advanced hepatic fibrosis in patients with HCV and ESRD. Methods In a retrospective study, we collected data on ratio of aspartate aminotransferase:alanine aminotransferase (AST:ALT), AST platelet ratio index (APRI), FIB-4 score, fibrosis index score, and King’s score from 139 patients with ESRD and HCV infection (mean age, 52.8 y; 76.3% male; 86.4% African American; 45.3% with increased level of ALT). Results were compared with findings from histologic analyses of biopsies (reference standard). The primary outcome was detection of advanced fibrosis, defined as either bridging fibrosis or cirrhosis. Area under the receiver operating characteristic (AUROC) curves were constructed and optimal cut-off values were determined for each test. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated. We repeated the analysis with stratification for normal levels of ALT (≤ 35 U/L for men and ≤ 25 u/L for women) and increased levels of ALT. Results FIB-4 scores identified patients with advanced fibrosis with an AUROC of 0.71 (95% CI, 0.61–0.80), the King’s score with an AUROC of 0.69 (95% CI, 0.58–0.80), and the APRI with and AUROC of 0.68 (95% CI, 0.59–0.79). The accuracy of these tests increased when they were used to analyze patients with increased levels of ALT. All tests produced inaccurate results when they were used to assess patients with normal levels of AST and ALT. Conclusions In patients with ESRD and HCV infection, FIB-4 scores, King’s scores, and the APRI identify those with advanced fibrosis with AUROC values ranging from 0.68–0.71. Accuracy increased modestly when patients with increased levels of ALT were tested, but the tests produced inaccurate results for patients with a normal level of ALT.

    更新日期:2020-02-20
  • Dietary Guidance for Patients with Inflammatory Bowel Disease from the International Organization for the Study of Inflammatory Bowel Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-15
    A. Levine; J.M. Rhodes; J.O. Lindsay; M.T. Abreu; M.A. Kamm; P.R. Gibson; C. Gasche; M.S. Silverberg; U. Mahadevan; R. Sigall Boneh; E. Wine; O.M. Damas; G. Syme; G.L. Trakman; C.K. Yao; S.I. Stockhamer; M.B. Hammami; L.C. Garces; J.D. Lewis

    Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn’s disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization of IBD (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with IBD to control and prevent relapse of IBD.

    更新日期:2020-02-20
  • Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-15
    C.R.H. Hedin; G. Sado; N. Ndegwa; E. Lytvyak; A. Mason; A. Montano-Loza; A. Gerussi; F. Saffioti; D. Thorburn; E. Nilsson; G. Larsson; B.A. Moum; K.N. van Munster; C.Y. Ponsioen; C. Levy; N.F. Nogueira; C.L. Bowlus; N. Gotlieb; A. Bergquist.

    Background Aims Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBD) are exposed to tumor necrosis factor (TNF) antagonists, because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD and their efficacy in treatment of IBD. Methods We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data available, clinical response, determined by the treating clinician or measurements of fecal. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors significantly associated with level of ALP during anti-TNF therapy. Results Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary non-response of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%, P=.035). Factors associated with lower ALP were normal ALP at baseline (P<.01), treatment with adalimumab (P=.090), and treatment in Europe (P=.083). Conclusions In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side-effects. Prospective studies are needed to further investigate the association between use of adalimumab and reduced serum levels of ALP. Background The authors assessed the effects of tumor necrosis factor (TNF) antagonists (adalimumab or infliximab) in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBD). Findings In a retrospective analysis of 141 patients with PSC and IBD, the authors observed response of IBD to treatment in 48% and remission of IBD to treatment in 23%, with no specific safety signals. Serum levels of alkaline phosphatase decreased with adalimumab but not infliximab. Implications for patient care Anti-TNF agents are effective in treatment of IBD in patients with PSC, although not as effective as in patients with non-PSC IBD. PSC should not be a contraindication to treatment with anti-TNF agents.

    更新日期:2020-02-20
  • No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-13
    Mingyang Song; I-Min Lee; JoAnn E. Manson; Julie E. Buring; Rimma Dushkes; David Gordon; Joseph Walter; Kana Wu; Andrew T. Chan; Shuji Ogino; Charles S. Fuchs; Jeffrey A. Meyerhardt; Edward L. Giovannucci

    Background & Aims The effects of vitamin D on risk of colorectal cancer precursors are not clear. We examined the influence of vitamin D supplementation on risk of colorectal adenomas and serrated polyps in a prespecified ancillary study of a large-scale prevention trial (the vitamin D and omegA-3 trial, VITAL) of individuals who were free of cancer and cardiovascular disease at enrollment. Methods In VITAL trial, 25,871 adults with no history of cancer or cardiovascular disease (12,786 men 50 y or older and 13,085 women 55 y or older) were randomly assigned to groups given daily dietary supplements (2000 IU vitamin D3 and 1 g marine n-3 fatty acid) or placebo. Patients were assigned to groups from November 2011 through March 2014 and the study ended on December 31, 2017. We confirmed conventional adenomas and serrated polyps by reviewing histopathology reports from participants who had reported a diagnosis of polyps and were asked by their doctors to return for a repeated endoscopy in 5 years or less. We calculated the odds ratios (ORs) and 95% CIs by logistic regression, after adjusting for age, sex, n-3 treatment assignment, and history of endoscopy at time of randomization. Results During a median follow-up of 5.3 years, we documented 308 cases of conventional adenomas in 12,927 participants in the vitamin D group and 287 cases in 12,944 participants in the placebo group (OR for the association of vitamin D supplementation with adenoma, 1.08; 95% CI, 0.92–1.27). There were 172 cases of serrated polyps in the vitamin D group and 169 cases in the placebo group (OR for the association of vitamin D supplementation with serrated polyp, 1.02; 95% CI, 0.82–1.26). Supplementation was not associated with polyp size, location, multiplicity, or histologic features. We found evidence for an interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D, measured in 15,787 participants. Among individuals with serum levels of 25-hydroxyvitamin D below 30 ng/mL, the OR associated with supplementation for conventional adenoma was 0.82 (95% CI, 0.60–1.13), whereas among individuals with serum levels of 25-hydroxyvitamin D above 30 ng/mL, the OR for conventional adenoma was 1.20 (95% CI, 0.92–1.55) (P for interaction=.07). There was a significant interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D in their association with advanced adenoma (P for interaction=.04). Conclusions Based on an ancillary study of data from the VITAL trial, daily vitamin D supplementation (2000 IU) was not associated with risk of colorectal cancer precursors in average-risk adults not selected for vitamin D insufficiency. A potential benefit for individuals with low baseline level of vitamin D requires further investigation. ClinicalTrials.gov number: NCT01169259

    更新日期:2020-02-20
  • Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-13
    Parambir S. Dulai; Siddharth Singh; Niels Vande Casteele; Joseph Meserve; Adam Winters; Shreya Chablaney; Satimai Aniwan; Preeti Shashi; Gursimran Kochhar; Aaron Weiss; Jenna L. Koliani-Pace; Youran Gao; Brigid S. Boland; John T. Chang; David Faleck; Robert Hirten; Ryan Ungaro; Dana Lukin; Charlie Cao

    Background & Aims We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). Methods We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. Results Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27–32 points), or high (CDST score, 33 points or more) probability of response vedolizumab exposure. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P<.001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P=.02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. Conclusions We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718

    更新日期:2020-02-20
  • Development and Validation of a Scoring System, Based on Genetic and Clinical Factors, to Determine Risk of Steatohepatitis in Asian Patients with Nonalcoholic Fatty Liver Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-13
    Bo Kyung Koo; Sae Kyung Joo; Donghee Kim; Seonhwa Lee; Jeong Mo Bae; Jeong Hwan Park; Jung Ho Kim; Mee Soo Chang; Won Kim

    Background & Aims There are no biomarkers of nonalcoholic steatohepatitis (NASH) that are ready for routine clinical use. We investigated whether an analysis of PNPLA3 and TM6SF2 genotypes (rs738409 and rs58542926) can be used to identify patients with nonalcoholic fatty liver disease (NAFLD), with and without diabetes, who also have NASH. Methods We collected data from the Boramae registry in Korea on 453 patients with biopsy-proven NAFLD with sufficient clinical data for calculating scores. Patients enrolled from May 2011 through March 2016 were assigned to cohort 1 (n = 302; discovery cohort) and patients enrolled thereafter were assigned to cohort 2 (n = 151; validation cohort). DNA samples were obtained from all participants and analyzed for the PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, SREBF2 rs133291 C>T, MBOAT7-TMC4 rs641738 C>T, and HSD17B13 rs72613567 adenine insertion (A-INS) polymorphisms. We used multivariable logistic regression analyses with stepwise backward selection to build a model to determine patients’ risk for NASH (NASH PT) using the genotype and clinical data from cohort 1 and tested its accuracy in cohort 2. We used the receiver operating characteristic (ROC) curve to compare the diagnostic performances of the NASH PT and the NASH scoring systems. Results We developed a NASH PT scoring system based on PNPLA3 and TM6SF2 genotypes, diabetes status, insulin resistance, and levels of aspartate aminotransferase and high-sensitivity C-reactive protein. NASH PT scores identified patients with NASH with an area under the ROC (AUROC) of 0.859 (95% CI, 0.817–0.901) in cohort 1. In cohort 2, NASH PT scores identified patients with NASH with an AUROC of 0.787 (95% CI, 0.715–0.860), which was significantly higher than the AUROC of the NASH score (AUROC, 0.729; 95% CI, 0.647–0.812; P=.007). The AUROC of the NASH PT score for detecting NASH in patients with NAFLD with diabetes was 0.835 (95% CI, 0.776–0.895) and in patients without diabetes was 0.809 (95% CI, 0.757–0.861). The negative predictive value of the NASH PT score <–0.785 for NASH in patients with NAFLD with diabetes reached 0.905. Conclusions We developed a scoring system, based on polymorphisms in PNPLA3 and TM6SF2 and clinical factors that identifies patients with NAFLD, with or without diabetes, who have NASH, with an AUROC value of 0.787. This system might help clinicians better identify NAFLD patients at risk for NASH.

    更新日期:2020-02-20
  • Predicting, Preventing, and Managing Treatment-related Complications in Patients With Inflammatory Bowel Diseases.
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-12
    Laurent Beaugerie; Jean-François Rahier; Julien Kirchgesner

    Risk of complications from specific classes of drugs for inflammatory bowel diseases (IBD) can be kept low by respecting contra-indications. Patients with IBD frequently develop serious infections, due to the disease itself or its treatment. At the time of diagnosis, patients’ vaccination calendars should be updated according to IBD guidelines—live vaccines should be postponed for patients receiving immunosuppressive drugs. Opportunistic infections should be detected and the vaccine against Pneumococcus should be given before patients begin immunosuppressive therapy. Thiopurines promote serious viral infections, in particular, whereas tumor necrosis factor (TNF) antagonists promote all types of serious and opportunistic infections. Severe forms of varicella can be prevented by vaccinating seronegative patients against varicella zoster virus. Detection and treatment of latent tuberculosis is mandatory before starting anti-TNF therapy and other new IBD drugs. Tofacitinib promotes herpes zoster infection in a dose- and age-dependent manner. Physicians should consider giving patients live vaccines against herpes zoster before they begin immunosuppressive therapy or a recombinant vaccine, when available, at any time point during treatment. Risk of thiopurine-induced lymphomas can be lowered by limiting the use of thiopurines in patients who are seronegative for Epstein-Barr virus (especially young men) and in older men. The risk of lymphoma related to monotherapy with anti-TNF agents is still unclear. There are no robust data on carcinogenic effects of recently developed IBD drugs. For patients with previous cancer at substantial risk of recurrence, physicians should try to implement a pause in the use of immunosuppressive therapy (except in patients with severe disease and no therapeutic alternative) and prioritize use of IBD drugs with lowest carcinogenic effects. Finally, sun protection and skin surveillance from the time of diagnosis are recommended.

    更新日期:2020-02-12
  • Efficacy of Single-Operator Cholangioscopy-guided Lithotripsy Compared With Large Balloon Sphincteroplasty in Management of Difficult Bile Duct Stones in a Randomized Trial
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-10
    Ji Young Bang; Bryce Sutton; Udayakumar Navaneethan; Robert Hawes; Shyam Varadarajulu

    Background & Aims Although single-operator cholangioscopy (SOC)-guided lithotripsy and large balloon sphincteroplasty (LBS)-based techniques are effective rescue measures, the ideal approach to management of difficult bile duct stones is unclear. We conducted a randomized trial to compare the effectiveness of SOC-guided lithotripsy and LBS-based approaches for endoscopic management of difficult bile duct stones. Methods Patients with difficult bile duct stones who failed retrieval using balloon or basket were randomly assigned to groups that received SOC-guided laser lithotripsy (SOC-LL, n=33) or LBS (n=33), from June 2016 through August 2018. When assigned treatment was unsuccessful, patients underwent mechanical lithotripsy before crossing over to the other group. The main outcome was treatment success, defined as ability to clear the duct in 1 session. Secondary outcomes were adverse events and treatment costs. Results A higher proportion of patients in the SOC-LL group had treatment success (93.9%) than in the LBS group (72.7%) (P=.021). On multiple logistic regression analysis, treatment success was significantly associated with use of SOC-LL (odds ratio [OR], 8.7; 95% CI, 1.3–59.3; P=.026), stone to extrahepatic bile duct ratio of 1 or less (OR, 28.8; 95% CI, 1.2–687.6; P=.038), and lack of a tapered bile duct (OR, 26.9; 95% CI, 1.3–558.2; P=.034). There was no significant difference between groups in adverse events (9.1% in the SOC-LL group vs 3.0% in the LBS group, P=.61) or overall treatment cost ($16,684 in the SOC-LL group vs $10,626 in the LBS group; P=.097). Conclusions In a randomized trial of patients with difficult bile stones that cannot be cleared by standard maneuvers, SOC-guided lithotripsy leads to duct clearance in a significantly higher proportion of patients than LBS-particularly when stone size exceeds the diameter of the extrahepatic bile duct. Adjunct lithotripsy might be required in patients with tapered distal bile duct, because LBS alone is less likely to be successful.

    更新日期:2020-02-10
  • Contribution of Surveillance Colonoscopy to Colorectal Cancer Prevention
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-02-01
    Paul F. Pinsky; Robert E. Schoen

    Background & Aims The contribution of surveillance colonoscopy, as opposed to that of initial colonoscopy examination, to prevention of colorectal cancer (CRC) is uncertain. We estimated the preventive effect of surveillance colonoscopy by applying the recently developed metric of adenoma dwell time avoided needed to prevent 1 CRC case (DTA). Methods We followed subjects in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial who underwent colonoscopies following positive findings from sigmoidoscopies (colonoscopy cohort, n=15,935) for CRC incidence for 10 years. The number and timing of adenomas removed during surveillance were measured in a subset (n=3492) of patients and extrapolated to the entire cohort to estimate the total avoided adenoma dwell time. A previously determined DTA value of 612 dwell years was applied to estimate the number of CRC cases prevented by surveillance. Proportional reduction in CRC was computed as CP/(CO+CP), where CO and CP are observed and estimated prevented cases, respectively. Results In the colonoscopy cohort of the PLCO, 2882 subjects had advanced adenomas (AAs), 572 had 3 or more non-advanced adenomas (NAA3+), 4496 had 1–2 non-advanced adenomas (NAA1-2), and 7985 had no adenoma (NA). The mean number of subsequent colonoscopy examinations over 10 years were 1.80 for subjects with AAs, 1.63 for subjects with NAA3+, and 1.46 for subjects with NAA1–2. Average years of avoided adenoma dwell time per subject were 4.0 for subjects with AAs, 5.5 for subjects with NAA3+, and 2.4 for subjects with NAA1–2. There were 56 cases of CRC in subjects with AAs, 4 cases of CRC in subjects with NAA3+, and 33 cases of CRC in subjects with NAA1–2. Estimated proportional reductions in CRC incidence were 25.0% in subjects with AAs (95% CI, 16%–34%), 34.4% in subjects with NAA1–2 (95% CI, 25%–40%), and 30.4% overall (in subjects with AAs, NAA3+, or NAA1–2; 95% CI, 25%–40%). Absolute CRC incidence reductions were 7.1 per 10,000 PY in subjects with AAs and 4.1 per 10,000 PY in subjects with NAA1-2. Conclusions Using the recently developed metric of DTA, we estimated that surveillance colonoscopy during 10 years of follow up (in the PLCO colonoscopy cohort) prevented 30% of CRC cases. Because the methodology for estimation is indirect, the true effect is uncertain.

    更新日期:2020-02-03
  • Prolonged Wireless pH Monitoring in Patients With Persistent Reflux Symptoms Despite Proton Pump Inhibitor Therapy
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-31
    Stephen Hasak; Rena Yadlapati; Osama Altayar; Rami Sweis; Emily Tucker; Kevin Knowles; Mark Fox; John Pandolfino; C. Prakash Gyawali

    Background & Aims Wireless pH monitoring measures esophageal acid exposure time (AET) for up to 96 hrs. We evaluated competing methods of analysis of wireless pH data. Methods Adult patients with persisting reflux symptoms despite acid suppression (n=322, 48.5±0.9 y, 61.7% women) from 2 tertiary centers were evaluated using symptom questionnaires and wireless pH monitoring off therapy, from November 2013 through September 2017; 30 healthy adults (controls; 26.9±1.5 y; 60.0% women) were similarly evaluated. Concordance of daily AET (physiologic <4%, borderline 4%–6%, pathologic>6%) for 2 or more days constituted the predominant AET pattern. Each predominant pattern (physiologic, borderline, or pathologic) in relation to data from the first day, and total averaged AET, were compared with other interpretation paradigms (first 2 days, best day, or worst day) and with symptoms. Results At least 2 days of AET data were available from 96.9% of patients, 3 days from 90.7%, and 4 days from 72.7%. A higher proportion of patients had a predominant pathologic pattern (31.4%) than controls (11.1%; P=.03). When 3 or more days of data were available, 90.4% of patients had a predominant AET pattern; when 2 days of data were available, 64.1% had a predominant AET pattern (P<.001). Day 1 AET was discordant with the predominant pattern in 22.4% of patients and was less strongly associated with the predominant pattern compared to 48 hour AET (P=.059) or total averaged AET (P=.02). Baseline symptom burden was higher in patients with a predominant pathologic pattern compared to a predominant physiologic pattern (P=.02). Conclusions The predominant AET pattern on prolonged wireless pH monitoring can identify patients at risk for reflux symptoms and provides gains over 24 hr and 48 hr recording, especially when results from the first 2 days are discordant or borderline.

    更新日期:2020-01-31
  • Integrated Psychological Care Reduces Healthcare Costs at a Hospital-Based Inflammatory Bowel Disease Service
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-31
    Taryn Lores; Charlotte Goess; Antonina Mikocka-Walus; Kathryn L. Collins; Anne L.J. Burke; Anna Chur-Hansen; Paul Delfabbro; Jane M. Andrews

    Background & Aims Inflammatory bowel diseases (IBD) are associated with high psychosocial burden and economic cost. Integrating psychological care into routine management might lead to savings. We performed a 2-year investigation of the effects of integrated psychological care in reducing healthcare use and costs. Methods We performed a prospective study of 335 adult patients treated at a hospital-based IBD service in Australia. Participants were recruited between September 2015 and August 2016 and completed screening instruments to evaluate mental health and quality of life. Data on healthcare use and costs for the previous 12 months were also collected. Patients found to be at risk for mental health issues were offered psychological intervention. Patients were followed up 12 months after screening (between September 2016 and August 2017). Results A significantly higher proportion of subjects at risk for mental health issues had presented to an emergency department in the 12 months before screening (51/182, 28%) compared to psychologically healthy subjects (28/152, 18%; X2(1)=4.23; P=.040). Higher levels of depression and general distress (but not anxiety) were related to increased odds of hospital admission (adjusted odds ratios, 1.07 and 1.05, respectively). Among the patients who accepted psychological intervention, the number who presented to emergency departments was reduced significantly in the 12 months after screening (follow-up) compared to the 12 months before screening (P=.047), resulting in a cost saving of AU$30,140 ($20,816 USD). A cost-benefit analysis of the integrated psychological care model revealed a net saving of AU$84,905 ($58,647 USD) over a 2-year period. Conclusions Risk for mental health issues is associated with higher healthcare costs in people with IBD. Providing integrated psychological care to individuals at risk for mental health issues can reduce costs, particularly by decreasing visits to emergency departments. Further studies are required to determine the best care to provide to reduce costs.

    更新日期:2020-01-31
  • Management of Patients With Immune Checkpoint Inhibitor-Induced Enterocolitis: a Systematic Review
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-31
    Michael Collins; Emilie Soularue; Lysiane Marthey; Franck Carbonnel

    Immune checkpoint inhibitors (ICIs) have improved the treatment of several cancers. These drugs increase T-cell activity and the anti-tumor immune response but also have immune-related adverse effects that can affect the gastrointestinal (GI) tract. These adverse effects are observed in 7%–30% of patients treated with ICIs. As the number of diseases treated with ICIs increases, gastroenterologists will see more patients with ICI-induced GI adverse events. We performed a systematic review of the incidence, risk factors, clinical manifestations, and management of the adverse effects of ICIs on the GI tract. Treatment with anti-CTLA4 often causes severe enterocolitis, whereas treatment with inhibitors of PDCD1 (also called PD1) has less frequent and more diverse adverse effects. Management of patients with GI adverse effects of ICIs should involve first ruling out other disorders, followed by assessment of severity, treatment with corticosteroids, rapid introduction of infliximab therapy for non-responders.

    更新日期:2020-01-31
  • Low Rate of Cancer Detection by Colonoscopy in Asymptomatic, Average-Risk Subjects with Negative Results From Fecal Immunochemical Tests
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-31
    George F. Longstreth; Daniel S. Anderson; Daniel S. Zisook; Jiaxiao M. Shi; Jane C. Lin

    Background & Aims It is not clear whether screening colonoscopies provide any benefit to persons with negative results from a fecal immunochemical test (FIT). We investigated detection of CRC by colonoscopy in asymptomatic, average-risk, FIT-negative subjects Methods We conducted a retrospective, population-based cohort study of 96,804 subjects with an initial negative result from a FIT at ages 50–75 y, from 2008 through 2014, who then underwent colonoscopy, using the Kaiser Permanente California databases. We identified participants diagnosed with CRC from January 1, 2008 through December 31, 2015 from a cancer registry. Subjects were followed until initial colonoscopy, health plan disenrollment, death, or December 31, 2015. We reviewed records from 400 randomly selected persons without CRC (controls) for risk features to estimate the proportion who underwent screening colonoscopy. We performed logistic regression to identify variables associated with CRC detection. Results Of 257 subjects with a diagnosis of CRC, 102 did not have a record of CRC risk factors; 86 of these patients (84.3%) had non-advanced-stage CRC (no regional node spread/distant metastases). Of the 400 controls, 299 (74.75%; 95% CI, 70.49%–79.01%) lacked CRC risk features, enabling estimation that 72,263 (mean age, 57.5±7.0 y; 54.5% female) had undergone screening colonoscopy. CRC was detected in 1.4 per 1000 persons after 1 FIT, without association with increasing FITs (P=.97). CRC was detected in 1.3 per 1000 persons in 2 y or less after the last FIT and in 4.4 per 1000 persons more than 2 y after the last FIT (P<.001). When the last FIT was 2 y earlier or less, CRC increased from 0.7 per 1000 persons age 50–59 y to 3.1 per 1000 persons older than 70 y. Age and time from the last FIT were associated with CRC, with adjusted odds ratios of 1.08 (95% CI, 1.05–1.11) and 2.76 (95% CI, 1.28–5.95), respectively. Conclusions In asymptomatic, average-risk persons with a negative result from a FIT, CRC is infrequent within 2 y after the last FIT (especially for persons younger than 60 y), usually non-advanced, and unrelated to the number of FITs performed.

    更新日期:2020-01-31
  • Changing Global Epidemiology of Inflammatory Bowel Diseases—Sustaining Healthcare Delivery into the 21st Century
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-31
    Ashwin N. Ananthakrishnan; Gilaad G. Kaplan; Siew C. Ng

    Crohn’s disease (CD) and ulcerative colitis (UC) have emerged as global diseases. They affect over 2 million individuals in the North America, 3.2 million in Europe, and millions more worldwide. The recent decades have been characterized by several important changes in the epidemiology of these diseases, in particularly an increasing incidence rates in newly industrialized countries experiencing a westernization of lifestyle. While rates of surgery have experienced a temporal decline attributable in part to increasing availability of medical treatments, earlier initiation of effective therapy, and changes in clinical practice, the healthcare costs associated with these diseases have continued to increase, in part due to costly therapies. Robust epidemiologic and experimental studies have defined the role of the external environment and microbiome on disease pathogenesis and have offered opportunities for disease prevention by modifying such factors. We propose several important steps that are necessary to provide globally sustainable IBD care in the 21st century.

    更新日期:2020-01-31
  • EFFICACY OF THERAPY FOR EOSINOPHILIC ESOPHAGITIS IN REAL-WORLD PRACTICE
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-25
    Emilio J. Laserna-Mendieta; Sergio Casabona; Edoardo Savarino; Antonia Perelló; Isabel Pérez-Martínez; Danila Guagnozzi; Jesús Barrio; Antonio Guardiola; Teresa Asensio; Susana de la Riva; Miriam Ruiz-Ponce; Juan Armando Rodríguez-Oballe; Cecilio Santander; Ángel Arias; Alfredo J. Lucendo

    Background & aims Topical steroids, proton pump inhibitors (PPIs), and dietary interventions are recommended first- and second-line therapies for eosinophilic esophagitis (EoE). We investigated differences in their effectiveness in a real-world, clinical practice cohort of patients with EoE. Methods We collected data on the efficacy of different therapies for EoE (ability to induce clinical and histologic remission) from the multicenter EoE CONNECT database—a database of patients with a confirmed diagnosis of EoE in Europe that began in 2016. We obtained data from 589 patients, treated at 11 centers, on sex, age, time of diagnosis, starting date of any therapy, response to therapy, treatment end dates, alternative treatments, and findings from endoscopy. The baseline endoscopy used for diagnosis of EoE; second endoscopy was performed to evaluate response to first-line therapies. After changes in treatment, generally because lack of efficacy, a last endoscopy was performed. The time elapsed between endoscopies depended on the criteria of attending physicians. Clinical remission was defined by a decrease of more than 50% in dysphagia symptom score; improvement in symptoms by less than 50% from baseline was considered as clinical response. Histologic remission was defined as a peak eosinophil count below 5 eosinophils/hpf. A peak eosinophil count between 5 and 14 eosinophils/hpf was considered histologic response. We identified factors associated with therapy selection and effectiveness using χ2 and multinomial logistic regression analyses Results PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%). Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%). Among the 344 patients who switched to a second-line therapy, dietary interventions were selected for 47.1% of patients, followed by PPIs (for 29.1%) and topical steroids (for 18.6%). Clinical and histologic remission or response was achieved by 80.7% of patients treated with topical steroids, 69.2% of patients given PPIs, and 41.7% of patients on empiric elimination diets. Multivariate analyses found the stricturing phenotype of EoE to be associated with selection of topical steroids over PPIs as the first-line therapy; lack of fibrotic features at initial endoscopy was associated with selection of elimination diets over topical steroids as a second-line therapy. The recruiting center was significantly associated with therapy choice; second-line treatment with topical steroids or PPIs were the only variables associated with clinical and histologic remission. Conclusions In an analysis of data from a large cohort of patients with EoE in Europe, we found topical steroids to be the most effective at inducing clinical and histologic remission, but PPIs to be the most frequently prescribed. Treatment approaches vary with institution and presence of fibrosis or strictures.

    更新日期:2020-01-26
  • Assessing National Trends and Disparities in Ambulatory, Emergency Department, and Inpatient Visits for Inflammatory Bowel Disease in the United States (2005–2016)
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-25
    Christopher Ma; Matthew Smith; Leonardo Guizzetti; Remo Panaccione; Gilaad G. Kaplan; Kerri L. Novak; Cathy Lu; Reena Khanna; Brian G. Feagan; Siddharth Singh; Vipul Jairath; Ashwin N. Ananthakrishnan

    Background Patients with inflammatory bowel diseases (IBD) require repeated healthcare encounters, although the focus of care differs when patients are seen in ambulatory, emergency department (ED), or inpatient settings. We examined contemporary trends and disparities in IBD-related healthcare visits. Methods We used data from the National Ambulatory Medical Care Survey, Nationwide Emergency Department Sample, and National Inpatient Sample to estimate the total number of annual IBD-related visits from 2005 through 2016. We performed logistic regression analyses to test temporal linear trends. Slope and differences in distributions of patient demographics were compared across time and treatment settings. Results From 2005 through 2016, approximately 2.2 million IBD-related ambulatory visits (95 CI, 1.9–2.5 million IBD-related ambulatory visits) occurred annually on average, increasing by 70.3% from the time period of 2005–2007 through the time period of 2008–2010, and decreasing by 19.8% from the time period of 2011–2013 through the time period of 2014–2016. An average of 115,934 IBD-related ED visits (95% CI, 113,758–118,111 IBD-related ED visits) and 89,111 IBD-related hospital discharges (95% CI, 87,416–90,807 IBD-related hospital discharges) occurred annually. Significant increases in the rate of IBD-related ED visits (3.2 visits/10,000 encounters, P<.0001) and hospital discharges (6.0 discharges/10,000 encounters, P<.0001) were observed from 2005 through 2016. The proportion of patients paying with private insurance decreased from 2005 through 2016, among all care settings. A greater proportion of young patients, patients with Crohn’s disease, non-white patients, and patients with Medicare or Medicaid used hospital-based vs ambulatory services. Conclusions In an analysis of data from 3 large databases, we found that although IBD-related ambulatory visits stabilized-to-decreased from 2005 through 2016, rates of ED use and admission to the hospital have continued to increase with changes in patient demographics, over time and among care settings.

    更新日期:2020-01-26
  • Sensitivity of fecal immunochemical test for colorectal cancer detection differs according to stage and location
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-25
    Tobias Niedermaier; Kaja Tikk; Anton Gies; Stefanie Bieck; Hermann Brenner

    Background & Aims Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening. FITs detect most CRCs. Although detection of CRC at early stages is most relevant for reducing CRC mortality, there is limited evidence for the stage-specific sensitivity of the FIT in CRC detection. We estimated stage- and location-specific sensitivities of a quantitative FIT in a large cohort of patients with CRC. Methods Fecal samples were collected before treatment from 435 patients with newly diagnosed CRC. Sensitivities of a quantitative FIT (FOB Gold, Sentinel Diagnostics; Milano, Italy) for tumors of different T stages and overall TNM stages (according to Union for International Cancer Control) were calculated at the cutoff recommended by the manufacturer (17 μg/g feces) and at alternative cutoffs, ranging from 10 to 40 μg/g feces, overall and stratified by tumor location. Results At the cutoff recommended by the manufacturer, the FIT detected T1 tumors with 52% sensitivity (95% CI, 37%–67%), T2 tumors with 79% sensitivity (95% CI, 68%–88%), T3 tumors with 93% sensitivity (95% CI, 89%–95%), and T4 tumors with 84% sensitivity (95% CI, 72%–92%) (Ptrend <.0001). The FIT detected stage I cancers with 68% sensitivity (95% CI, 57%–78%), stage II cancers with 92% sensitivity (95% CI, 87%–96%), stage III cancers with 82% sensitivity (95% CI, 73%–89%), and stage IV cancers with 89% sensitivity (95% CI, 80%–95%) (Ptrend 0.01). The FIT detected T1 colorectal tumors with sensitivity values that were 22%–52% lower than for tumors of other T stages and stage I CRC with sensitivity values that were 11%–33% lower than for later-stage CRCs, at any of the evaluated cutoff values. The FIT detected T1 and stage I CRCs in the distal colon with sensitivity values of 32% and 52%, respectively. Conclusions Although the FIT identifies patients with CRC with overall high sensitivity, it can miss approximately one-third of stage I CRCs. Studies are needed to increase noninvasive detection of early-stage CRC.

    更新日期:2020-01-26
  • Dallas Steatosis Index Identifies Patients With Nonalcoholic Fatty Liver Disease
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-23
    Scott McHenry; Yikyung Park; Jeffrey D. Browning; Gregory Sayuk; Nicholas O. Davidson

    Background & Aims Tools have been developed to determine risk for nonalcoholic fatty liver disease (NAFLD) based on imaging, which does not always detect early-grade hepatic steatosis. We aimed to develop a tool to identify patients with NAFLD using 1H MR spectroscopy (MRS). Methods We collected data from the Dallas Heart Study—a multi-ethnic, population-based, probability study of adults (18–65 y) that comprised an in-home medical survey; collection of fasting blood samples; MRS images to measure cardiac mass/function, abdominal subcutaneous/visceral adiposity; and quantification of hepatic triglyceride concentration, from 2000 through 2009. NAFLD were defined as 5.5% or more liver fat and we excluded patients with more than moderate alcohol use; 737 patients were included in the final analysis. We performed binary multivariable logistic regression analysis to develop a tool to identify patients with NAFLD and evaluate interactions among variables. We performed an internal validation analysis using 10-fold cross validation. Results We developed the Dallas Steatosis Index (DSI) to identify patients with NAFLD based on level of alanine aminotransferase, body mass index, age, sex, levels of triglycerides and glucose, diabetes, hypertension, and ethnicity. The DSI discriminated between patients with vs without NAFLD with a C-statistic of 0.824. The DSI outperformed 4 risk analysis tools, based on net reclassification improvement and decision curve analysis. Conclusions We developed an index, called the DSI, which accurately identifies patients with NAFLD based on MRS data. The DSI requires external validation, but might be used in development NAFLD screening programs, in monitoring progression of hepatic steatosis, and in epidemiology studies.

    更新日期:2020-01-24
  • Hepatitis flare-related decompensation is associated with better outcomes in patients with chronic hepatitis B
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-23
    Ming-Ling Chang; Jur-Shan Cheng; Rong-Nan Chien; Yun-Fan Liaw

    Background & Aims The effects of baseline hepatitis flares (alanine transaminase level >5 times the upper limit of normal) on the outcomes of cirrhotic chronic hepatitis B (CHB) patients with decompensation treated with nucleos(t)ide analogues (Nucs) remain elusive; thus, we aimed to investigate these effects. Methods This 16-year cohort study monitored 511 consecutive cirrhotic CHB patients treated with Nucs for decompensation. Results Of the 511 patients, 399 (78.1%) were males, and 300 (58.7%) had baseline flares. Patients with flares had higher baseline levels of hepatitis B virus (HBV) DNA (6.44±1.52 vs. 6.08±1.46 log10 IU/mL, p=0.003), quantitative hepatitis B surface antigen, total bilirubin (bili-t), prolonged prothrombin time (δPT), platelet counts (108.0±42.9 vs. 83.6±44.7 103/μL, p<0.001) and genotype B infection rates but lower neutrophil-to-lymphocyte ratios (NLRs) (6.14±9.18 vs. 9.12±1.36, p=0.019), rates of hepatitis B e antigen positivity, ascites, esophageal varices (EVs), and splenomegaly and cumulative incidence of mortality or liver transplantation (46.5 vs. 73.2%, p<0.001) than the patients without flares despite their similar short-term (<3 months) outcomes. EVs [95% confidence interval (CI) of odds ratio: 0.067-0.406], ascites (0.178-0.969), levels of bili-t (1.041-1.269) and δPT (1.033-1.168) and platelet counts (1.00-1.018) were independently associated with baseline flares. After matching patients with and without baseline flares through propensity score matching method, flares (95% CI hazard ratio: 0.317-0.76) and levels of NLR (1.027-1.591) and δPT (1.052-1.423) were independently associated with the cumulative incidence of mortality or liver transplantation. Conclusions In decompensated, cirrhotic CHB patients treated with Nucs, a baseline hepatitis flare was independently associated with favorable long-term (>3 months) outcomes.

    更新日期:2020-01-23
  • RECURRENCE IS RARE FOLLOWING COMPLETE ERADICATION OF INTESTINAL METAPLASIA IN PATIENTS WITH BARRETT’S ESOPHAGUS AND PEAKS AT 18 MONTHS
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-23
    Sachin Wani; Samuel Han; Vladimir Kushnir; Dayna Early; Daniel Mullady; Hazem Hammad; Brian Brauer; Adarsh Thaker; Violette Simon; Eze Ezekwe; Thomas Hollander; Mariah Wood; Amit Rastogi; Steven Edmundowicz; V. Raman Muthusamy; Srinadh Komanduri

    Background & Aims There have been few studies of the long-term durability of complete eradication of intestinal metaplasia (CE-IM) in patients with Barrett’s esophagus (BE)-related neoplasia who received endoscopic eradication therapy (EET). Data are needed to guide surveillance interval protocols and identify patients at risk for recurrence. We assessed the rate of recurrence of intestinal metaplasia and dysplasia, histologic features, and outcomes after recurrence of CE-IM, and identified factors associated with recurrence. Methods We performed a prospective study of 807 patients with BE who underwent EET, which produced CE-IM, at 4 tertiary-care referral centers, from January 2013 to October 2018. Kaplan-Meier estimates of cumulative incidence rates (IR) of recurrence were calculated for up to 5 years following CE-IM and were stratified by baseline level of histology. Density estimates of recurrence were used to determine the change in the rate of recurrence over time. We conducted logistic regression analysis to identify factors associated with recurrence. Results Intestinal metaplasia recurred in 121 patients (15%; IR, 5.2/100 person-years), and dysplasia recurred in 36 patients (4.5%; IR, 1.6/100 person-years), after a median follow-up time of 2317 person-years. The rate of recurrence was not constant and the time to any recurrence converged to a normal distribution; recurrences peaked at 1.6 y after patients had CE-IM. Baseline high-grade dysplasia or intramucosal cancer (adjusted odds ratio [aOR], 4.19), presence of reflux symptoms (aOR, 12.1) or hiatal hernia (aOR, 13.8), and number of sessions required to achieve CE-IM (aOR, 1.8) were associated with recurrence. Conclusions In a prospective study of a large cohort of patients with BE undergoing EET, we found a low rate of recurrence after CE-IM. The rate of recurrence peaked at 1–2 y after CE-IM. These findings indicate that aggressive surveillance might not be necessary more than 1 y after CE-IM and should be considered in surveillance guidelines. Clinicaltrials.gov no: NCT02634645

    更新日期:2020-01-23
  • Positioning therapies in ulcerative colitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-23
    Silvio Danese; Gionata Fiorino; Laurent Peyrin-Biroulet

    Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease (IBD) that affects the large intestine. Several therapeutic drug classes are available for the treatment of UC: salicylates, corticosteroids, thiopurines, calcineurin inhibitors, anti-tumor necrosis factor (TNF) agents, anti-adhesion molecules, and, more recently, small molecules directed against the Janus kinase (JAK) pathways, and ustekinumab (anti IL12/23). Other drugs are currently in development, and they will be probably available for UC patients in the near future. Several therapeutic algorithms have been proposed for the treatment of UC patients, yet these are predominantly based on expert opinions rather than high-quality evidence, mainly due to the lack of head-to-head trials, especially for monoclonal antibody and small molecule therapies. The optimal position of therapies in these algorithms remains unclear. Therefore, we conducted this review of the literature to provide an up-to-date overview of the available evidence on this topic.

    更新日期:2020-01-23
  • Shedding Light on Hemostasis in Patients With Inflammatory Bowel Diseases
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2020-01-20
    Jeremy Lagrange; Patrick Lacolley; Denis Wahl; Laurent Peyrin-Biroulet; Véronique Regnault

    Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis, possibly due to changes in blood cells and molecules involved in hemostasis. They have increased platelet counts and reactivity as well as increased platelet-derived large extracellular vesicles. Coagulation is continuously activated in patients with IBD, based on measured markers of thrombin generation, and the anticoagulant functions of endothelial cells are damaged. Furthermore, fibrinogen is increased and fibrin clots are denser. However, pathogenesis of thrombosis in patients with IBD appears to differ from that of patients without IBD. Patients with IBD also take drugs that might contribute to risk of thrombosis, complicating the picture. We review the features of homeostasis that are altered in patients with IBD and possible mechanisms of this relationship.

    更新日期:2020-01-21
  • Recommendations for Successful Transition of Adolescents With Inflammatory Bowel Diseases to Adult Care
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-08
    Jordan M. Shapiro; Hashem B. El-Serag; Cassandra Gandle; Cynthia Peacock; Lee A. Denson; Laurie N. Fishman; Ruben Hernaez; Jason K. Hou

    Adolescents and young adults diagnosed with inflammatory bowel diseases (IBDs) in pediatric care are vulnerable during their transition to adult care. There are 6 core elements of transition from pediatric to adult IBD care. We identified gaps in this transition and make recommendations for clinical practice and research. There have been few studies of transition policy (core element 1) or studies that tracked and monitored patients through the transition (core element 2). Several studies have assessed transition readiness (core element 3), but instruments for assessment were not validated using important outcomes such as disease control, health care use, adherence, quality of life, or continuity of care. There have been no studies of best practices for transition planning (core element 4), including how to best educate patients and facilitate gradual shifts in responsibility. A small number of longitudinal studies have investigated transfer of care (core element 5), but these were conducted outside of the United States; these studies found mixed results in short- and intermediate-term outcomes after transition completion (core element 6). We discuss what is known about the transition from pediatric to adult care for IBD, make recommendations to improve this process, and identify areas for additional research.

    更新日期:2020-01-13
  • Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: A Systematic Review
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-25
    Paulo Gustavo Kotze; Fox E. Underwood; Aderson Omar Mourão Cintra Damião; Jose Geraldo P. Ferraz; Rogerio Saad-Hossne; Martin Toro; Beatriz Iade; Francisco Bosques-Padilla; Fábio Vieira Teixeira; Fabian Juliao-Banos; Daniela Simian; Subrata Ghosh; Remo Panaccione; Siew C. Ng; Gilaad G. Kaplan

    Background & Aims The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean. Methods We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn’s disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis. Results The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991–1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990–2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012–2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001–2003 and 6.2% in 2004–2014. Conclusions In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.

    更新日期:2020-01-13
  • Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-05
    Laura Turco; Candid Villanueva; Vincenzo La Mura; Juan Carlos García-Pagán; Thomas Reiberger; Joan Genescà; Roberto J. Groszmann; Barjesh C. Sharma; Carlo Merkel; Christophe Bureau; Edilmar Alvarado; Juan Gonzalez Abraldes; Agustin Albillos; Rafael Bañares; Markus Peck-Radosavljevic; Salvador Augustin; Shiv K. Sarin; Jaime Bosch; Guadalupe García-Tsao

    Background & Aims In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites. Methods We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites. Results Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective β-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22–0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32–0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16–0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29–0.75). No heterogeneity was observed among studies. Conclusions In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective β-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.

    更新日期:2020-01-13
  • Efficacy of Epicutaneous Immunotherapy in Children With Milk-Induced Eosinophilic Esophagitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-14
    Jonathan M. Spergel; Okan U. Elci; Amanda B. Muir; Chris A. Liacouras; Benjamin J. Wilkins; Deirdre Burke; Megan O. Lewis; Terri Brown-Whitehorn; Antonella Cianferoni

    Background & Aims Eosinophilic esophagitis (EoE) is caused by an immune response to specific food allergens. There are no approved therapies beyond avoidance of the allergen(s) or treatment of inflammation. Epicutaneous immunotherapy (EPIT) reduces features of eosinophilic gastrointestinal disease in mice and pigs. We performed randomized, placebo-controlled study to determine the safety and efficacy of EPIT with Viaskin milk in children with milk-induced EoE. Methods In a double-blind study, 20 children (4–17 years old) with milk-induced EoE were randomly assigned to groups given EPIT with Viaskin milk (n = 15) or placebo (n = 5) for 9 months during a milk-free period, followed by milk-containing diet for 2 months with EPIT. Then, subjects underwent upper endoscopy analysis, biopsies were collected, and maximum esophageal eosinophil counts were determined and was the primary endpoint. After upper endoscopy, patients were given open-label EPIT for 11 months (open-label phase). The subjects were allowed to consume milk if they had maximum values of fewer than 10 eosinophils/high-power field (eos/hpf); otherwise, they remained on a milk-free diet until the last 2 months of the open-label phase. Results In the intent to treat population, there was no significant difference between the Viaskin milk group in mean eos/hpf (50.1 ± 43.97 eos/hpf) vs the placebo group (48.20 ± 56.98 eos/hpf). However, in the per-protocol population (7 patients given Viaskin milk and 2 patients given placebo), patients given Viaskin milk patients had a significantly lower mean eos/hpf count (25.57 ± 31.19) than patients given placebo (95.00 ± 63.64) (p = .038). At the end of the open-label phase, 9 of 19 evaluable subjects had mean values of fewer than 15 eos/hpf (47% response). The number of adverse events did not differ significantly between the Viaskin milk and placebo groups; there was 1 serious adverse event in the placebo group. Conclusions In a pilot study of pediatric patients with EoE given EPIT with Viaskin milk or placebo for 11 months, we found no significant difference between groups for the maximum eosinophil count at the end of the study. However, findings from a per-protocol analysis indicate that Viaskin milk can reduce eos/hpf. At study completion, 47% of patients who continued open-label Viaskin milk for an additional 11 months had mean values of fewer than 15 eos/hpf. ClinicalTrials.gov no: NCT02579876

    更新日期:2020-01-13
  • Increased Incidence and Mortality of Gastric Cancer in Immigrant Populations from High to Low Regions of Incidence: A Systematic Review and Meta-Analysis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-30
    Baldeep S. Pabla; Shailja C. Shah; Juan E. Corral; Douglas R. Morgan

    Background & Aims Gastric cancer is the leading cause of infection-related cancer death and the third-leading cause of cancer death worldwide. The effect of immigration on gastric cancer risk is not well-defined but might be helpful for screening or surveillance endeavors. We performed a systematic review and meta-analysis to define the risk of gastric cancer in immigrants from high-incidence regions to low-incidence regions (including Western Europe, Australia, Brazil, Canada, Israel, and the United States). Methods We searched MEDLINE and EMBASE databases, from January 1980 to January 2019, for studies that identified immigrants from high-incidence regions of gastric cancer, provided clear definitions of immigrant and reference populations, and provided sufficient data to calculate gastric cancer incidence and gastric cancer-related mortality. We performed meta-analyses of standardized incidence ratios (SIR) for first-generation immigrants from high- to low-incidence regions, stratified by immigrant generation, sex, and anatomic and histologic subtype, when data were available. Results We identified 38 cohort studies that met our inclusion criteria. All 13 studies of 21 distinct populations reported significantly increased SIRs for gastric cancer in first-generation foreign-born immigrants (men SIR range, 1.24–4.50 and women SIR range, 1.27–5.05). The pooled SIR for immigrants with all types of gastric cancer was 1.66 (95% CI, 1.52–1.80) for men and 1.83 (95% CI, 1.69–1.98) for women. Nine studies from 2 high-incidence populations (the former Soviet Union and Japan) reported an increased gastric cancer standardized mortality ratio in first-generation immigrants who migrated to regions of low incidence (former Soviet Union immigrants, 1.44–1.91 for men and 1.40–2.56 for women). Conclusions Immigrants from regions with a high incidence of gastric cancer to regions of low incidence maintain a higher risk of gastric cancer and related mortality, based on a comprehensive systematic review and meta-analysis. Assessment of immigrant generation along with other risk factors might help identify high-risk populations for prevention and therapeutic interventions.

    更新日期:2020-01-13
  • Risk of Gastrointestinal Bleeding Increases With Combinations of Antithrombotic Agents and Patient Age
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-18
    Neena S. Abraham; Peter A. Noseworthy; Jonathan Inselman; Jeph Herrin; Xiaoxi Yao; Lindsey R. Sangaralingham; Gabriella Cornish; Che Ngufor; Nilay D. Shah

    Background & Aims The safety of different antithrombotic strategies for patients with 1 or more indication for antithrombotic drugs has not been determined. We investigated the risk and time frame for gastrointestinal bleeding (GIB) in patients prescribed different antithrombotic regimens. We proposed that risk would increase over time and with combination regimens, especially among elderly patients. Methods We performed a retrospective analysis of nationwide claims data from privately insured and Medicare Advantage enrollees who received anticoagulant and/or antiplatelet agents from October 1, 2010, through May 31, 2017. Patients were stratified by their prescriptions (anticoagulant alone, antiplatelet alone, or a combination) and by their primary diagnosis (atrial fibrillation, ischemic heart disease, or venous thromboembolism). The 1-year GIB risk was estimated using parametric time-to-event survival models and expressed as annualized risk and number needed to harm (NNH). Results Our final analysis included 311,211 patients (mean ages, 67 years for monotherapy and 69.8 years for combination antithrombotic therapy). There was no significant difference in the proportion of patients with bleeding after anticoagulant or antiplatelet monotherapy (∼3.5%/year). Combination antithrombotic therapy increased GIB risk compared with anticoagulant (NNH, 29) or antiplatelet (NNH, 31) monotherapy, regardless of the patients’ diagnosis or time point analyzed. Advancing age was associated with increasing 1-year probability of GIB. Patients prescribed combination therapy were at the greatest risk for GIB, especially after the age of 75 years (GIB occurred in 10%–17.5% of patients/y). Conclusions In an analysis of nationwide insurance and Medicare claims data, we found GIB to occur in a higher proportion of patients prescribed combinations of anticoagulant and antiplatelet agents compared with monotherapy. Among all drug exposure categories and cardiovascular conditions, the risk of GIB increased with age, especially among patients older than 75 years.

    更新日期:2020-01-13
  • Abdominal Pain in Children Develops With Age and Increases With Psychosocial Factors
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-04-19
    Michael P. Jones; Åshild Faresjö; Alissa Beath; Tomas Faresjö; Johnny Ludvigsson

    Background & Aims Functional gastrointestinal disorders are highly prevalent, cause significant suffering, and are costly to society. Pain is a central feature of 2 of the most common functional gastrointestinal disorders: irritable bowel syndrome and functional dyspepsia. Although these disorders have been well studied in adults, their etiology is poorly understood. We sought to identify early life factors associated with the development of abdominal pain in children (age, 2–12 y). Methods We collected data from the All Babies in Southeast Sweden study of 1781 children, born from October 1, 1997, through October 31, 1999, whose families answered questions about abdominal pain and risk factors at birth, 1 year, 2.5 years, 5 years, 8 years, and 10 to 12 years. We used latent growth curve models to evaluate risk factors for development of abdominal pain. The primary outcomes were prevalence of abdominal pain and associated factors. Results The prevalence of abdominal pain increased linearly with age in the study cohort, increasing by approximately 6% per year. Psychosocial variables associated with slope of the growth curve included lower emotional control at age 2 years (P = .005), parental concern for the child at age 2 years (P = .02), and measures of parental stress (P = .004). Nonvaginal birth was associated with a reduced slope of the growth curve (P = .03). Conclusions In a study of children in Sweden, we found early psychosocial environment and mode of delivery at birth was associated with development of childhood abdominal pain. Factors associated with development of the early immune system, identified in previous recall-based research, were not supported by data from this study. These findings have important implications for the prevention of abdominal pain in children and later in life.

    更新日期:2020-01-13
  • Clinical and Pathological Characterization of Lynch-Like Syndrome
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-17
    María Dolores Picó; Adela Castillejo; Óscar Murcia; Mar Giner-Calabuig; Miren Alustiza; Ariadna Sánchez; Leticia Moreira; María Pellise; Antoni Castells; Marta Carrillo-Palau; Teresa Ramon y Cajal; Alexandra Gisbert-Beamud; Gemma Llort; Carmen Yagüe; Adriá López-Fernández; Cristina Alvarez-Urturi; Joaquin Cubiella; Laura Rivas; Rodrigo Jover

    Background & Aims Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins—this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. Methods We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. Results We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. Conclusions Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.

    更新日期:2020-01-13
  • Fecal Incontinence Diagnosed by the Rome IV Criteria in the United States, Canada, and the United Kingdom
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-30
    William E. Whitehead; Magnus Simren; Jan Busby-Whitehead; Steve Heymen; Miranda A.L. van Tilburg; Ami D. Sperber; Olafur S. Palsson

    Background & Aims The diagnostic criteria for fecal incontinence (FI) were made more restrictive in the Rome IV revision. We aimed to determine the characteristics of FI patients defined by the Rome IV criteria, assess how FI frequency and amount affect quality of life, identify risk factors, and compare prevalence values among countries. Methods We performed an internet-based survey of 5931 subjects in the United States, Canada, and the United Kingdom, from September to December 2015. Subjects were stratified by country, sex, and age. Responders answered questions about diagnosis, health care use, and risk factors. We performed multivariate linear regression analysis to identify risk factors for FI. Results FI was reported by 957 subjects (16.1%) but only 196 (3.3%) fulfilled the Rome IV criteria. Frequency of FI was less than twice a month for 672/957 subjects (70.2%) and duration was less than 6 months for 285/957 subjects (29.8%). Quality of life was significantly impaired in all subjects with FI compared to subjects with fecal continence. The strongest risk factors for FI were diarrhea, urgency to defecate, and abdominal pain. FI was more prevalent in the United States than in the United Kingdom. Between-country differences were due to less diarrhea and urgency in the United Kingdom. Conclusions Rome IV FI prevalence is lower than previous estimates because the new criteria exclude many individuals with less frequent or short duration FI. These excluded patients have impaired quality of life. It might be appropriate to make a diagnosis of FI for all patients with FI ≥2 times in 3 months and to provide additional information on frequency, duration, and amount of stool lost to assist clinicians in treatment selection.

    更新日期:2020-01-13
  • Increased Gut Permeability in First-degree Relatives of Children with Irritable Bowel Syndrome or Functional Abdominal Pain
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-14
    Mark McOmber; Danny Rafati; Kevin Cain; Sridevi Devaraj; Erica M. Weidler; Margaret Heitkemper; Robert J. Shulman

    Background & Aims Increased gut permeability might contribute to the pathogenesis of irritable bowel syndrome or functional abdominal pain (IBS or FAP). We investigated whether siblings and parents of children with IBS or FAP have increased gut permeability. Methods We performed permeability tests (using sucrose, lactulose, mannitol, and sucralose) on 29 siblings and 43 parents of children with IBS or FAP, and 43 children (controls) and 42 parents of controls, from primary and secondary care. Permeability studies were repeated in 7 siblings and 37 parents of children with IBS or FAP and 23 controls and 36 parents of controls following ingestion of 400 mg of ibuprofen. Percent recovery of sucrose was calculated based on analyses of urine collected overnight; the lactulose/mannitol ratio and percent recovery of sucralose were based on analyses of urine samples collected over a 24-hour period. Results When we controlled for age, sex, and family membership, siblings of children with IBS or FAP had increased small bowel permeability (urinary lactulose/mannitol ratio) vs controls (P = .004). There was no difference in gastroduodenal (percent sucrose recovery) or colonic (percent sucralose recovery) permeability between groups. Similarly, parents of children with IBS or FAP also had increased small bowel permeability, compared with parents of controls (P = .015), with no differences in gastric or colonic permeability. After administration of ibuprofen, gastroduodenal and small bowel permeability tended to be greater in IBS or FAP siblings (P = .08) and gastroduodenal permeability tended to be greater in IBS or FAP parents (P = .086). Conclusions Siblings and parents of children with IBS or FAP have increased baseline small intestinal permeability compared with control children and their parents. These results indicate that there are familial influences on gastrointestinal permeability in patients with IBS or FAP.

    更新日期:2020-01-13
  • Epidemiological, Clinical, and Psychological Characteristics of Individuals with Self-reported Irritable Bowel Syndrome Based on the Rome IV vs Rome III Criteria
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-31
    Christopher J. Black; Yan Yiannakou; Lesley A. Houghton; Alexander C. Ford

    Objectives Few studies have examined the effects of applying the Rome IV criteria for irritable bowel syndrome (IBS) vs the previous standard, the Rome III criteria. We conducted a cross-sectional survey of individuals who self-identify as having IBS to examine this issue. Methods We collected complete demographic, symptom, mood, and psychological health data from 1375 adults who self-identified as having IBS, but were not recruited from a referral population. We applied the Rome III and the Rome IV criteria simultaneously to examine what proportion met each of these diagnostic criteria for IBS. We measured the level of agreement between the Rome III and Rome IV criteria, and assessed for presence of an alternative functional bowel disorder in individuals who no longer met diagnostic criteria for IBS with the more restrictive Rome IV criteria. Finally, we compared characteristics of individuals who met only Rome III criteria with those who met Rome IV criteria. Results In total, 1080 of 1368 individuals (78.9%) with IBS met the Rome III criteria. In contrast, 811 of 1373 individuals (59.1%) with IBS met the Rome IV criteria. Agreement between the criteria was only moderate (Kappa = 0.50). Among those who no longer had IBS according to the Rome IV criteria, 33 (11.5%) met Rome IV criteria for functional constipation, 118 (41.3%) for functional diarrhea, 68 (23.8%) for functional abdominal bloating or distension, and 67 (23.4%) for an unspecified functional bowel disorder. Individuals with Rome IV-defined IBS had more severe symptoms, and a higher proportion had a mood disorder and evidence of poor psychological health, compared with individuals who only met the Rome III criteria for IBS (P < .001). Conclusions The characteristics of people who believe they have IBS differ between those who meet criteria as defined by Rome IV vs Rome III, including the spectrum of disease severity. Studies are needed to determine how these changes will affect outcomes of clinical trials.

    更新日期:2020-01-13
  • Variation Among Patients With Crohn’s Disease in Benefit vs Risk Preferences and Remission Time Equivalents
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-14
    Meenakshi Bewtra; Shelby D. Reed; F. Reed Johnson; Frank I. Scott; Erin Gilroy; Robert S. Sandler; Wenli Chen; James D. Lewis

    Background & Aims Patients with Crohn’s disease (CD) must make decisions about their treatment. We aimed to quantify patients’ preferences for different treatment outcomes and adverse events. We also evaluated the effects of latent class heterogeneity on these preferences. Methods An online stated-preference survey was completed by 812 individuals with CD in the Crohn’s and Colitis Foundation Partners cohort (IBD Partners). Patients were given information on symptoms and severity of active disease; duration of therapy with corticosteroids; and risks of serious infection, cancer and surgery. Patients were asked to assume that their treatment was not working and to choose an alternative therapy. The primary outcome was remission-time equivalents (RTE) of a given duration of symptom severity or treatment-related risk. Latent class choice models identified groups of patients with dominant treatment-outcome preferences and associated patient characteristics with these groups. Results Latent class analysis demonstrated 3 distinct groups of survey responders whose choices were strongly influenced by avoidance of active symptoms (61%), avoidance of corticosteroid use (25%), or avoidance of risks of cancer, infection or surgery (14%) when choosing a therapy. Class membership was correlated with age, sex, mean short CD activity index score and corticosteroid avoidance. RTEs in each latent class differed significantly from the mean RTEs for the overall sample, although the symptom-avoidant class most closely approximated the overall sample. Conclusions In an online survey of patients with CD, we found substantial heterogeneity in preference for medication efficacy and risk of harm. Physicians and regulators should therefore not assume that all patients have mean-value preferences—this could result in significant differences in health-technology assessment models.

    更新日期:2020-01-13
  • Supplementary Anal Imaging by Magnetic Resonance Enterography in Patients with Crohn’s Disease Not Suspected of Having Perianal Fistulas
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-25
    Pyeong Hwa Kim; Seong Ho Park; Kiok Jin; Byong Duk Ye; Yong Sik Yoon; Jong Seok Lee; Hyun Jin Kim; Ah Young Kim; Chang Sik Yu; Suk-Kyun Yang

    Background & Aims Few data are available to guide the use of anal imaging for patients with Crohn’s disease (CD) who are not suspected of having perianal fistulas. We aimed to evaluate the role of anal imaging supplementary to magnetic resonance enterography (MRE) in these patients. Methods In a prospective study, we added a round of anal MR imaging (MRI), collecting axial images alone, to MRE evaluation of 451 consecutive adults who were diagnosed with or suspected of having CD but not believed to have perianal fistulas. Images were examined for perianal tracts; if present, colorectal surgeons reexamined patients to identify external openings or perianal inflammation or abscess. Patients were followed and data were collected on dedicated treatment for perianal fistulas or abscess. We calculated the diagnostic yield for anal MRI, associated factors, and outcomes of MRI-detected asymptomatic perianal tracts. Results A total of 440 patients (mean age, 29.6±8.9 years) met the inclusion criteria. Anal MRI revealed perianal tracts in 53 patients (12%; 95% CI, 9.3%–15.4%). Surgeons however did not identify any lesions that required treatment. The asymptomatic tracts were mostly single unbranched (83%), inter-sphincteric (72%), or had a linear dark signal at the tract margin (79%). Younger age at MRE, female sex, and CD activity index scores of 220–450 were independently associated with detection of perianal tracts. MRI detection of asymptomatic tracts was independently associated with later development of perianal fistulas or abscess that required treatment: 17.8% cumulative incidence at 37 months and an adjusted hazard ratio of 3.06 (95% CI, 1.01–9.27; P = .048). Conclusions In a prospective study of patients with CD, we found that adding anal MRI evaluation to MRE resulted in early identification of patients at risk for perianal complications.

    更新日期:2020-01-13
  • Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-06-18
    Somashekar G. Krishna; Phil A. Hart; Ahmad Malli; Andrew J. Kruger; Sean T. McCarthy; Samer El-Dika; Jon P. Walker; Mary E. Dillhoff; Andrei Manilchuk; Carl R. Schmidt; Timothy M. Pawlik; Kyle Porter; Christina A. Arnold; Zobeida Cruz-Monserrate; Darwin L. Conwell

    Background & Aims Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. Methods We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. Results The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. Conclusions In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

    更新日期:2020-01-13
  • Comparative Efficacy and Speed of Onset of Action of Infliximab vs Golimumab in Ulcerative Colitis
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-05-18
    Siddharth Singh; James A. Proudfoot; Parambir S. Dulai; Ronghui Xu; Brian G. Feagan; William J. Sandborn; Vipul Jairath

    Background & Aims With several options available for patients with moderate–severe ulcerative colitis (UC), rapidity of symptom resolution could be an important differentiator. We compared the efficacy and speed of onset of action of infliximab vs golimumab induction therapy using patient-level data from phase 3 trials (ACT-1, ACT-2, and PURSUIT-SC). Methods We compared differences in proportions of patients who achieved the composite outcome of a rectal bleeding score=0 and stool frequency score ≤1 (patient-reported outcome 2 remission) at weeks 2 and 6 of treatment with standard-dose infliximab vs golimumab using logistic generalized estimating equation. Overall efficacy for inducing clinical remission (Mayo clinic score <3) was compared using logistic regression. Analyses were adjusted for sex, disease extent, baseline clinical and endoscopic severity, C-reactive protein, albumin, body weight and concomitant medications (immunomosuppressives, corticosteroids, and 5-aminsalicylates). Results Trial populations were similar and no differences were observed among the placebo groups in the studies. A significantly higher proportion patients treated with infliximab than golimumab achieved patient-reported outcome 2 remission at week 2 (35% vs 30%; adjusted odds ratio [OR], 1.71; 95% CI, 1.15–2.55) and at week 6 (50.0% vs 38.9%; adjusted OR, 2.0; 95% CI, 1.40–2.94). Infliximab-treated patients were also significantly more likely to achieve clinical remission than golimumab-treated patients (adjusted OR, 3.01; 95% CI, 1.95–4.70), with consistent findings in patients with moderate or severe UC. Conclusions Based on a patient-level analysis of data from phase 3 trials, infliximab resolves symptoms more rapidly and has greater efficacy for inducing remission than golimumab in patients with moderate-to-severe UC.

    更新日期:2020-01-13
  • Optimizing Outcomes of Single-Operator Cholangioscopy–Guided Biopsies Based on a Randomized Trial
    Clin. Gastroenterol. Hepatol. (IF 7.958) Pub Date : 2019-07-24
    Ji Young Bang; Udayakumar Navaneethan; Muhammad Hasan; Bryce Sutton; Robert Hawes; Shyam Varadarajulu

    Background & Aims Although single-operator cholangioscopy is considered to be the most sensitive method for tissue acquisition in patients with indeterminate bile duct strictures (IBDS), methods are needed to optimize the specimen collection and processing techniques. We aimed to determine the optimal method for specimen processing and identify the number of biopsies required to establish a definitive diagnosis. Methods Patients with IBDS were randomly assigned to groups that underwent specimen processing using the onsite (n = 32) or offsite (n = 30) method. The primary outcome was to compare operating characteristics of onsite vs offsite specimen processing techniques. The secondary outcome was number of biopsies needed to establish definitive diagnosis. A final diagnosis was established at surgery or after a minimum clinical follow-up period of 18 months Results The final diagnosis was benign disease in 33 patients and malignancy in 29 patients. There were no significant differences between the offsite and onsite groups in diagnostic accuracy (90% vs 87.5%; P=.99), sensitivity (76.9% vs 75%; P=.99), specificity (100% vs 100%; P=.99), positive predictive value (100% vs 100%; P=.99), or negative predictive value (85% vs 80%; P=.99). Although diagnoses were established by analysis of a median of 1 biopsy in the onsite cohort (interquartile range, 1–1.5), the diagnostic accuracy was identical (90%) in each group, regardless of whether 3 or 4 biopsies were collected from each patient in the offsite cohort. Conclusions In a prospective comparative study, we found that centers without onsite cytopathology support that analyze 3 single-operator cholangioscopy-guided biopsies of a biliary stricture and process the specimens offsite make the correct diagnosis for 90% of cases. ClinicalTrials.gov, Number: NCT01815619.

    更新日期:2020-01-13
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