High mucosal cytomegalovirus DNA helps predict adverse short-term outcome in acute severe ulcerative colitis

( Saransh Jain ),( Divya Namdeo ),( Pabitra Sahu ),( Saurabh Kedia ),( Peush Sahni ),( Prasenjit Das ),( Raju Sharma ),( Vipin Gupta ),( Govind Makharia ),( Lalit Dar ),( Simon Pl Travis ),( Vineet Ah 대한장연구학회 2021 Intestinal Research Vol.19 No.4

Background/Aims: Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. Methods: Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ in-dex (ulcerative colitis index of severity >6 at day 1+fecal calprotectin >1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. Results: Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0-2,700,000] vs. 116 copies/mg [0-27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load >2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6-39.7; P<0.01) and AIIMS’ index (OR, 39.8; 95% CI, 4.4-364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC. Conclusions: High mucosal CMV DNA ( >2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC. (Intest Res 2021;19:438-447)

Are Truelove and Witts criteria for diagnosing acute severe colitis relevant for the Indian population?A prospective study

Saransh Jain,Saurabh Kedia,Sawan Bopanna,Dawesh P Yadav,Sandeep Goyal,Peush Sahni,Sujoy Pal,Nihar Ranjan Dash,Govind Makharia,Simon P. L. Travis,Vineet Ahuja 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: Truelove and Witts criteria have been used to define acute severe colitis since the 1950s. However, hemoglobin(an additional criterion of the definition) levels in the general population in developing countries are lower than in the population of developed countries. We aimed to determine the relevance of Truelove and Witts criteria in the Indianpopulation. Methods: Consecutive patients with acute severe colitis satisfying the Truelove and Witts criteria, hospitalized ata single center between April 2015 and December 2016 were included. All patients received intravenous corticosteroids and 16 required colectomy. The hemoglobin levels at admission were subsequently excluded from the classification criteria, and the effect this had on the criteria for diagnosis was determined. Results: Out of 61 patients of acute severe colitis diagnosed according to the original Truelove and Witts criteria, 12 patients (20%) had 1 additional criterion, 33 (54%) had 2 additionalcriteria and 16 (26%) had 3 or more additional criteria in addition to 6 or more blood stained stools on admission. On excludinghemoglobin as an additional criterion from the Truelove and Witts definition, all patients still met the criteria for acute severecolitis. Conclusions: Truelove and Witts criteria can be used to define acute severe colitis in India, despite lower mean hemoglobinin the native population.

High risk of tuberculosis during infliximab therapy despite tuberculosis screening in inflammatory bowel disease patients in India

( Ashish Agarwal ),( Saurabh Kedia ),( Saransh Jain ),( Vipin Gupta ),( Sawan Bopanna ),( Dawesh P Yadav ),( Sandeep Goyal ),( Venigalla Pratap Mouli ),( Rajan Dhingra ),( Govind Makharia ),( Vineet A 대한장연구학회 2018 Intestinal Research Vol.16 No.4

Background/Aims: The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. Methods: This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). Results: Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5-48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0-84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. Conclusions: There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX. (Intest Res 2018;16:588-598)

Efficacy and tolerability of exclusive enteral nutrition in adult patients with complicated Crohn’s disease

( Sanchit Sharma ),( Arti Gupta ),( Saurabh Kedia ),( Samagra Agarwal ),( Namrata Singh ),( Sandeep Goyal ),( Saransh Jain ),( Vipin Gupta ),( Pabitra Sahu ),( Sudheer Kumar Vuyyuru ),( Bhaskar Kante 대한장연구학회 2021 Intestinal Research Vol.19 No.3

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI >70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2-6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260-320] vs. 240 [180-280], P=0.001) and 8 weeks (baseline 290 [260-320] vs. 186 [160-240], P=0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n=4), B2 (n=18), and B3 (n=9) phenotypes were 50%, 78.8%, and 100% respectively (log-rank test, P=0.093). The response rates at 8 weeks with polymeric (n=8) and semi-elemental diet (n=23) were 75% and 82.6% respectively (log-rank test, P=0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002-1.017; P=0.046) predicted response to EEN. Conclusions: EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN. (Intest Res 2021;19:291-300)

Familial aggregation of inflammatory bowel disease in patients with ulcerative colitis

( Akshita Gupta ),( Sawan Bopanna ),( Saurabh Kedia ),( Dawesh Prakash Yadav ),( Sandeep Goyal ),( Saransh Jain ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2017 Intestinal Research Vol.15 No.3

Background/Aims: Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. Methods: Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. Results: Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn`s disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). Conclusions: The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations. (Intest Res 2017;15:388-394)

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring

Peeyush Kumar,Sudheer K. Vuyyuru,Prasenjit Das,Bhaskar Kante,Mukesh Kumar Ranjan,David Mathew Thomas,Sandeep Mundhra,Pabitra Sahu,Pratap Mouli Venigalla,Saransh Jain,Sandeep Goyal,Rithvik Golla,Shubi 대한장연구학회 2023 Intestinal Research Vol.21 No.4

Background/Aims: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD).Methods: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.Results: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (<i>P</i><0.001), postoperative recurrence (<i>P</i>=0.001) and high IL-7R expression (<i>P</i><0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; <i>P</i><0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; <i>P</i>=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (<i>P</i><0.001), and high C-reactive protein (<i>P</i><0.001), OSM (<i>P</i><0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; <i>P</i>=0.001) on multivariate analysis respectively. Conclusions: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.