Background The Lémann index (LI) is the first instrument developed to measure cumulative structural bowel damage in Crohn’s disease (CD).1 We here report its validation. Methods This was an international, multicentre, prospective cross-sectional observational study. At each centre, 10 inclusions, stratified by known or suspected CD location and duration, were planned. Clinical examination and abdominal MRI had to be performed in all patients, and upper endoscopy, colonoscopy, and pelvic MRI according to CD location. Upper tract (UT), small bowel (SB), colon/rectum (CR), and anus (AN) were divided into 3, 20, 6 and 1 segments, respectively. History of previous surgery was collected per segment. For each segment, 1 gastroenterologist and 1 radiologist per centre, identified the presence of predefined stricturing and/or penetrating lesions of maximal severity (grade 1 to 3) at each investigation. They provided a damage evaluation for each non-resected segment ranging from 0 to 10, 10 corresponding to the damage of a completely resected segment. Investigator organ damage evaluation was calculated as the sum of segmental damage evaluations. Finally, investigators provided a global damage evaluation from 0 to 10 for each patient according to the 4 organ damage scores, calculated as a function of investigator organ damage evaluations, resections and a total number of segments. The correlation between the investigator global damage evaluation and the LI was high on the construction sample, since coefficients to derive the LI were estimated by maximising this correlation, and is expected to be lower on data obtained in new patients by new investigators. Thus, the LI would be validated if the linear regression model of investigator global damage evaluation on LI shows a still high correlation. The same applies to investigator damage evaluation of each organ and each organ component of the LI. Results 134 patients were included in 15 centres, 7 to 10 per centre. Correlation coefficients between investigator organ damage evaluation and each organ component of the LI were 0.91, 0.96, 0.95, and 0.81, for UT, SB, CR and AN, respectively. The correlation coefficient between investigator global damage evaluation and the LI was 0.98 (Figure 1). Proportions of the investigator organ damage evaluation variance explained by each organ component of the LI were 82%, 91%, 89%, 65%, for UT, SB, CR, AN, respectively. This proportion was 96% for the investigator global damage evaluation and the LI. Conclusion The Lémann index is now a validated index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials. Reference

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Background Patients with IBD are at higher risk for non-alcoholic fatty liver disease (NAFLD) comparing to general population. Complex pathogenesis of NAFLD in IBD may be related to disease-specific risk factors such as chronic inflammation, steroid exposure, drug induced hepatotoxicity, malnutrition and alteration of gut microbiota, which is emerging as a major factor in the pathogenesis of NAFLD. The goal of the study was to investigate factors associated with NADLF and advanced liver fibrosis (ALF) in patients with CD and UC. Methods This is a retrospective study on IBD patients without extraintestinal manifestations and known liver disease. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥ 36, and ALF was defined as FIB-4 ≥ 2.67. Predictors of NAFLD development were analysed using Kaplan–Meier and Cox regression analyses. Results In this retrospective study, we have included 225 IBD patients; 72.4% (n = 163) patients with CD and 27.6% (n = 62) patients with UC (median age 41.2 yr, 53.7% males) which were observed for a median of 4.6 years. There were 63.1% (n = 142) patients with normal BMI, 27.6% (n = 62) overweight and 9.3% (n = 21) obese patients. Obese patients had the highest HIS score 43.9 ± 5.9, following with overweight 37.8 ± 5.7 and normal BMI 30 ± 4.3 kg/m2, p < 0.001. During the follow-up obese and overweight patients had higher risk of developing NAFLD comparing to patients with normal BMI (obese HR = 11.1 95% CI 4.3–28.3 and overweight HR = 5.55 95% CI 3.4–9.1, Logrank test p < 0.001) (Figure 1). Regarding FIB-4 score there, was no difference among different BMI categories (p = 0.192), and there was no difference in ALF development in the follow-up period (Logrank test p = 0.91). In Cox proportional-hazards regression significant predictors for NAFLD development were dyslipidaemia HR=2.11, 95% CI 1.2–3.7, overweight HR=6 95% CI 3.6–10, and obesity HR=13.4, 95% CI 7–35. Conclusion NAFLD is frequent comorbidity in patients with CD and UC, which can lead to development of advanced liver fibrosis. Our results show that patients with IBD have a high risk of NAFLD development, whereas the increased risk for ALF was not observed. Overweight and obese patients and those with dyslipidemia should be closer monitored due to significantly higher risk of NAFLD. This study points out the complexity disease-specific risk factors and importance of better stratifying IBD patients at risk of NAFLD and advanced liver fibrosis.

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Background In Crohn’s disease (CD), the extensive and potentially transmural inflammation results in increased activity of both matrix metalloproteases (MMPs) and serine proteases, causing a higher degree of intestinal tissue remodelling. This increased proteolytic activity could potentially cause degradation and loss of function of mechanical and functional matrix proteins, such as elastin. Therefore, we sought to investigate the association between biomarkers of elastin degradation and the disease activity in CD patients. Methods Seventy-two CD patients and 29 healthy donors (HD) were included in the study. Disease activity was determined according to the Crohn’s disease activity index score (CDAI >150) and/or a faecal calprotectin (fCALP >250). Additionally, CD patients were endoscopically assessed according to the simple endoscopic score (SES) for CD. Different protease derived biomarkers of elastin degradation: protease-3 (ELP-3), MMP-7 (ELM-7) and cathepsin-G (EL-CG) was measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) was applied for the statistical analysis. Results The levels of ELP-3 was significantly elevated in active CD when compared with the HD (p < 0.001), and inactive CD (p < 0.01). Levels of EL-G were significantly elevated when comparing active CD and HD (p < 0.05), with the same result observed for the levels of EL-CG when comparing active CD and the HD (p < 0.05). Endoscopically, ELP-3 was shown significantly elevated in moderate–to-severe CD patients when compared with the HD (p < 0.01). Conclusion In this study, measurements of the elastin degradation markers were capable of differentiating between CD patients with either a clinically active or biochemically active disease, with the biomarker levels being significantly highest in the patients with an active disease. This was also the case when assessing endoscopic disease activity, where the protease-3-derived biomarker levels were highest in patients of moderate-to-severe disease activity. As such, the data provide indications of the beneficial use of these serum biomarkers as additional disease activity assessment tools for CD patients.