Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn’s disease in tuberculosis endemic areas

Karan Sachdeva,Peeyush Kumar,Bhaskar Kante,Sudheer K. Vuyyuru,Srikant Mohta,Mukesh K. Ranjan,Mukesh K. Singh,Mahak Verma,Govind Makharia,Saurabh Kedia,Vineet Ahuja 대한장연구학회 2023 Intestinal Research Vol.21 No.2

Background/Aims: Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. Methods: Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. Results: Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. Conclusions: In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis

( Saurabh Kedia ),( Raju Sharma ),( Sudheer Kumar Vuyyuru ),( Deepak Madhu ),( Pabitra Sahu ),( Bhaskar Kante ),( Prasenjit Das ),( Ankur Goyal ),( Karan Madan ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2022 Intestinal Research Vol.20 No.2

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB. (Intest Res 2022;20:184-191)

Use of thiopurines in inflammatory bowel disease: an update

( Arshdeep Singh ),( Ramit Mahajan ),( Saurabh Kedia ),( Amit Kumar Dutta ),( Abhinav Anand ),( Charles N. Bernstein ),( Devendra Desai ),( C. Ganesh Pai ),( Govind Makharia ),( Harsh Vardhan Tevethia 대한장연구학회 2022 Intestinal Research Vol.20 No.1

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential. (Intest Res 2022;20:11-30)

Prospective validation of CD4⁺CD25⁺FOXP3⁺ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn’s disease

( Ritika Rampal ),( Saurabh Kedia ),( Mohamad Nahidul Wari ),( Deepak Madhu ),( Amit Kumar Singh ),( Veena Tiwari ),( V. Pratap Mouli ),( Srikant Mohta ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2021 Intestinal Research Vol.19 No.2

Background/Aims: Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4⁺CD25⁺FOXP3⁺ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients. Methods: Seventy treatment naïve patients of CD (n=23) and ITB (n=47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients. Results: Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33-50] vs. 24.9 [interquartile range, 14.4-29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65-0.89) and a FOXP3⁺ cutoff value of >31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n=33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68-0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD. Conclusions: The current findings validate that the increased frequency of CD4⁺CD25⁺FOXP3⁺ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD. (Intest Res 2021;19:232-238)

Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India

( Parnita Harsh ),( Vipin Gupta ),( Saurabh Kedia ),( Sawan Bopanna ),( Sucharita Pilli ),( Surendernath ),( Govind Kumar Makharia ),( Vineet Ahuja ) 대한장연구학회 2017 Intestinal Research Vol.15 No.1

Background/Aims: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD. Methods: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn`s disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%). Results: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively. Conclusions: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers. (Intest Res 2017;15:97-102)