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

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 (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<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; P=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.

Long-term outcomes of anti-tumor necrosis factor therapy and surgery in nonperianal fistulizing Crohn's disease.

BACKGROUND: Unlike perianal fistula, long-term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF. METHODS: We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018. RESULTS: Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow-up: 47 months (interquartile range [IQR]:26-76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti-tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% (n = 9). Overall probability of maintaining response was similar between the anti-TNF and surgical groups (95.2% vs 82.4%; 71% vs 76%; and 63% vs 69%% [P = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty-one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti-TNF therapy). Long-term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti-TNF therapy. Two patients (3.7%) developed malignancy (one - enteroenteric, one - colovesical). CONCLUSION: Anti-TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula-associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy.

Atrophic gastritis with high prevalence of Helicobacter pylori is a predominant feature in patients with dyspepsia in a high altitude area.

BACKGROUND: Dyspepsia is a common symptom in residents of Leh, a high-altitude region in Ladakh, India. Helicobacter pylori related gastritis is a common cause of such symptoms. However data regarding this association at high altitudes is sparse. AIM: To investigate the demographic, endoscopic and histopathology findings in patients presenting with dyspeptic symptoms in the high-altitude region of Leh. Methods: A cross-sectional study was done in 84 patients with dyspeptic symptoms, attending the outpatient department of local government hospital in Leh. Demographic details, endoscopy, histopathology of upper gastrointestinal biopsies and microbiology culture of gastric/duodenal aspirates were studied. RESULTS: The mean age was 38.4 years with 42% being males. Indigenous foods with high-salt content were consumed by 75% of patients. Epigastric pain was the most frequent symptom (in 96%) and pain radiating to the back was another peculiar symptom seen in 49% of patients. The predominant finding on endoscopy was antral gastritis in 71% of patients. Nodular gastritis was seen in 18% of patients. H. pylori was documented in 93% and histopathology revealed mild-to-moderate inflammation in 93% and mild-to-moderate atrophy in 90% of patients. Colonization with Gram-negative bacilli was observed in gastric/duodenal aspirate cultures. CONCLUSION: Dyspepsia at high-altitude commonly presents as pain radiating to the back with a very high (90%) prevalence of H. pylori, endoscopic findings of antral gastritis and nodular gastritis, and atrophic gastritis in biopsies. Further investigations are needed to determine whether these observations are related to the high-altitude or the high-salt content in their diet and also whether these further translate to carcinogenesis.