Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn’s disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to test new rapid culture methods for MAP in human subjects and to assess the degree of viable culturable MAP bacteremia in CD patients compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients (two of the patients with CD had concurrent ulcerative colitis (UC)) and 140 non-CD controls (14 patients in this group had UC only). Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with a positive Phage assay (4/9) or MAP culture (5/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.
There was high correlation between CE and ileocolonoscopy scores for the assessment of mucosal disease activity over time; however, there were no correlations between endoscopic scores and clinical parameters. The use of serial capsule endoscopy for the assessment of small-bowel CD is feasible and valid. (www.clinicaltrials.gov; NCT01942720).
Background and Aims: Reactivation of chronic HBV (CHB-R) is well described in immunosuppressed individuals. We share our experienceof CHB-R in immunocompetent individuals Methods: From our HBV registry data of over 700 patients enrolled between 2008 to 2017, patients presenting with acute hepatitic illness (ALT > 10 × ULN) were identified. CHB-R was diagnosed if patiens already had HBsAg positivity for more than six months prior to acute illness or Patients also had signs of chronic liver disease in addition to acute hepatic illness or If at presentation, IgMAnti HBc was positive only in low titers, eAb was positiveat presentation, and HBV DNA was more than 105 logs. All patients had a detailed history to look for HBV transmission route and duration, family history of HBV, alcohol consumption recorded. Signs of chronic liver disease clinically, on USG wnd OGD scopy were looked for. All patient underwent CBC, Liver chemestries, HBV serology and in some cases HBV DNA. All patients also HIV Ab, HCV and HEV Ab testing. Antiviral agents were started if CHB-R was a consideration. Choice of antiviral was random. Results: 23 patients had CHB-R.11 were male and 12 female.3 had HBsAg positivity for more than six months prior to acute illness, while 20 presented for the first time with positive HBs Ag status. 11 patients has signs of chronic liver disease in addition to acute illness. IgM Anti HBc was below 50 in 11, more than 200 in 2 and titers not available in 10 patients. 6 patients wereHBeAg positive and 17 were negative. Anti HBeAb was positive in all patients at presentation. HBV DNA was more than 105log in 5, less than 104 log in 4 and not done in remaining. 21 patients recieved antiviral agents.19 out of 23 became HBs Ag negative and 4 continued to remain HBsAg positive. Conclusions: Spontaneous reactivation of CHB in immunocompetent individuals is uncommon but has very good prognosis. Early antiviral therapy is indicated in these patients. The author has none to declare.
Background: Vedolizumab (VDZ), a humanised monoclonal antibody that targets α4β7 integrin, is approved for moderately to severely active Crohn's disease (CD) and ulcerative colitis. The GEMINI open-label extension (OLE) trial is an ongoing study investigating the long-term safety of VDZ (NCT00790933). Here we report the 5-year exploratory analyses of effectiveness and safety in patients (pts) with CD who had completed GEMINI 2 [1] and were enrolled in GEMINI OLE. Methods: Analyses included pts who had responded to VDZ induction at Week (Wk) 6 and received VDZ maintenance (every 8 or 4 wks; data were combined) to Wk 52 of GEMINI 2, followed by VDZ every 4 wks in GEMINI OLE. Pts with 248 wks of cumulative VDZ treatment (data were collected from 22 May 2009 to 21 May 2015) were assessed for clinical response (decrease in Harvey–Bradshaw Index [HBI] of ≥3 points from baseline [BL]), clinical remission (HBI ≤4) and health-related quality of life (HRQoL), including IBD Questionnaire (IBDQ) and Euro Quality of Life-5D visual analogue scale (EQ-5D VAS). Safety was also assessed. Results: Of 308 pts in GEMINI 2 who responded to VDZ induction at Wk 6 and received VDZ in maintenance, 146 (47%) completed VDZ maintenance and were enrolled in GEMINI OLE (anti-TNFα-naïve n=81; anti-TNFα failure n=57). At the time of this analysis, 61 pts had completed 248 wks of cumulative VDZ treatment, 58 had discontinued (n=11 [19%] due to lack of continued benefit) and 27 are ongoing (have not yet reached 248 wks of treatment). Of pts with data at Wk 248 (n=61), 95% had clinical response and 89% were in remission (Table). HRQoL improvements were observed at Wk 248, with mean change from BL IBDQ and EQ-5D-VAS scores of 59.4 and 29.8, respectively. In the safety population, 134 pts had adverse events (AEs); 15 discontinued due to AEs. Serious AEs were reported in 41 pts (in 3 pts these were drug-related; 8 pts discontinued as a consequence of serious AEs). One death (not drug-related; motor accident) was reported. Table 1. Effectiveness outcomes in patients with CD and cumulative VDZ exposure for up to 248 wks Conclusions: Long-term VDZ therapy (∼5 years) was associated with clinical benefits including clinical response, clinical remission and HRQoL improvements in pts with moderately to severely active CD who responded at Wk 6, completed GEMINI 2 and enrolled in OLE. Long-term VDZ therapy was associated with no unanticipated AEs, and the safety profile was consistent with that previously observed in a 3-year interim analysis of the OLE study. References: [1] Sandborn WJ, Feagan BG, Rutgeerts P, et al., (2013), Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease, N Engl J Med, 711–21
