Adil A. Abdalla

Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C

Objective Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Design 70 treatment-naive patients were randomised to 4 weeks of ribavirin (1000–1200 mg/d) or none, followed by PEG-IFNα-2a and ribavirin at standard doses and durations. Patients were also randomised to a liver biopsy 24 h before or 6 h after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results After 4 weeks of ribavirin monotherapy, hepatitis C virus (HCV) levels decreased by 0.5±0.5 log10 (p=0.009 vs controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting ISG induction by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological, response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs 22% non-responders, p=0.01; early virological response, 100% vs 68%, p=0.03; sustained virological response 83% vs 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusions Ribavirin is a weak antiviral but its clinical effect seems to be mediated by a separate, indirect mechanism, which may act to reset IFN-responsiveness in HCV-infected liver.

Outcomes of Patients With Microscopic Colitis Treated With Corticosteroids: A Population-Based Study

OBJECTIVES:To evaluate the outcomes of corticosteroid-treated microscopic colitis (MC) in a population-based cohort, and to compare these outcomes in patients treated with prednisone or budesonide.METHODS:A historical cohort study of Olmsted County, Minnesota residents diagnosed with collagenous or lymphocytic colitis (LC) between 1986 and 2010 was performed using the Rochester Epidemiology Project.RESULTS:Of 315 patients with MC, 80 (25.4%) were treated with corticosteroids. The median age at colitis diagnosis was 66.5 years (range: 16–95) and 78.7% were female. Forty patients (50%) had LC and 40 (50%) had collagenous colitis. Prednisone was used in 17 patients (21.2%) and budesonide in 63 (78.8%); 56 (75.6%) had complete response and 15 (20.3%) had partial response. Patients treated with budesonide had a higher rate of complete response than those treated with prednisone (82.5 vs. 52.9%; odds ratio, 4.18; 95% CI, 1.3–13.5). Six patients were lost to follow-up. The remaining 74 had a median follow-up of 4 years (range 0.2–14). Fifty patients out of the 71 who responded (70.4%) had a recurrence after corticosteroid discontinuation. Patients treated with budesonide were less likely to recur than those treated with prednisone (hazard ratio, 0.38; 95% CI, 0.18–0.85; P=0.02). After 397 person years of follow-up in the 73 patients with long-term data, 47 (64.4%) required maintenance with corticosteroids.CONCLUSION:Patients with MC often respond to corticosteroid therapy, but with a high relapse rate. Budesonide had a higher response rate and a lower risk of recurrence than prednisone.

Durability of Antibody Response Against Hepatitis B Virus in Healthcare Workers Vaccinated as Adults

BACKGROUND Follow-up studies of recipients of hepatitis B vaccine from endemic areas have reported loss of antibody to hepatitis B surface antigen (anti-HBs) in a high proportion of persons vaccinated at birth. In contrast, the long-term durability of antibody in persons vaccinated as adults in nonendemic areas is not well defined. We aimed to assess the durability of anti-HBs among healthcare workers (HCWs) vaccinated as adults and response to a booster among those without protective levels of antibody. METHODS Adult HCWs aged 18-60 at the time of initial vaccination were recruited. All were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HBs level. HCWs with anti-HBs <12 mIU/mL were offered a booster and levels were measured 1, 7, and 21 days afterward. RESULTS Anti-HBs levels were <12 mIU/mL in 9 of 50 (18%), 13 of 50 (26%), and 14 of 59 (24%) HCWs 10-15, 16-20, and >20 years postvaccination, respectively, (P = ns). Four HCWs were anti-HBc positive; none had HBsAg. By logistic regression, older age at vaccination was the only predictor of inadequate anti-HBs level (P = .0005). Thirty-four of 36 subjects with inadequate anti-HBs levels received a booster and 32 (94%) developed levels >12 mIU/mL within 3 weeks. CONCLUSIONS Anti-HBs levels decrease after 10-31 years and fall below a level considered protective in approximately 25% of cases. The rapid and robust response to a booster vaccine suggests a long-lasting amnestic response. Hepatitis B vaccination provides long-term protection against hepatitis B and booster vaccination does not appear to be necessary in HCWs. Clinical Trials Registration. NCT01182311.

The learning curve for interpretation of oesophageal high‐resolution manometry: a prospective interventional cohort study

High‐resolution manometry has become the preferred choice of oesophagologists for oesophageal motor assessment, but the learning curve among trainees remains unclear.

Coeliac disease screening is suboptimal in a tertiary gastroenterology setting

Background and aims Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice. Methods Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics. Results 616 consecutive patients (49±0.6 years, range 16–87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p<0.0001); CD screening rate was highest in the luminal GI clinic (p=0.002). Of 145 patients screened, 4 patients (2.4%) had serology consistent with CD, of which 2 were proven by duodenal biopsy. Using this proportion, an additional 5 patients might have been diagnosed in 191 untested patients with indications for CD screening. Conclusions More than 50% of patients in a tertiary GI clinic have indications for CD screening, but <50% of indicated cases are screened. Case-finding techniques therefore are suboptimal, constituting a gap in patient care and an important target for future quality improvement initiatives.

Which Chronic Upper Airway Symptoms May Be Due to Acid Reflux

G A A b st ra ct s NSAID use and erosive esophagitis and/or esophageal strictures. Most studies were published 10 years ago and significant heterogeneity was seen between studies. Limited data suggest that use of NSAIDs was not significantly increased in patients with esophageal injury compared with controls, with a magnitude of effect size smaller than that reported with gastroduodenal ulcers. More evidence is required to have a clearer picture of esophageal injury caused by NSAIDs.

S1920 Predictive Validity and Responsiveness of the Mayo Dysphagia Questionnaire- 30 for the Outcome of Erosive Reflux Esophagitis

Predictive Validity and Responsiveness of the Mayo Dysphagia Questionnaire30 for the Outcome of Erosive Reflux Esophagitis Judith L. McElhiney, Felicity Enders, Michael D. Crowell, K.Robert Shen, Robert C. Miller, Catherine R. Weiler, Rayna Grothe, Dawn L. Francis, Gianrico Farrugia, Melissa M. Kuntz, Nancy Diehl, Matthew R. Lohse, Amindra S. Arora, Darlene E. Graner, Nicholas J. Talley, G. Richard Locke, Joseph A. Murray, Jeffrey A. Alexander, Timothy J. Beebe, Adil A. Abdalla, Joanna M. Peloquin, April Grudell, Ganapathy A. Prasad, Yvonne Romero