Ana Gutiérrez1,2, Pedro Zapater2, Oriol Juanola2, Laura Sempere1, Marifé García3, Raquel Laveda4, Antonio Martínez4, Michael Scharl5, José M González-Navajas2, José Such6, Reiner Wiest7, Gerhard Rogler5, Rubén Francés2,8. 1. Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain. 2. CIBERehd, Instituto de Salud Carlos III, Madrid, Spain. 3. Servicio Digestivo, Hospital Universitario de Elche, Alicante, Spain. 4. Hospital Clínico Universitario de San Juan, Alicante, Spain. 5. Division of Gastroenterology and Hepatology, University Hospital Zìrich, Zìrich, Switzerland. 6. Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE. 7. Department of Gastroenterology, University Clinic for Visceral Medicine, Inselspital, Bern, Switzerland. 8. Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de Alicante, Spain.
Abstract
OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to-relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS: BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation.
OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CDpatients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to-relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS: BactDNA is an independent risk factor of relapse at 6 months in CDpatients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation.
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Authors: Paula Piñero; Oriol Juanola; Ana Gutiérrez; Pedro Zapater; Paula Giménez; Anna Steinert; Laura Sempere; José M González-Navajas; Jan H Niess; Rubén Francés Journal: J Mol Med (Berl) Date: 2017-09-06 Impact factor: 4.599
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