Browsing by Organization "Division of Gastroenterology, Department of Medicine, Helsinki University Central Hospital"

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  • af Björkesten, Clas-Göran (Helsingin yliopisto, 2014)
    In Crohn s disease (CD), achievement of mucosal healing has been associated with good outcome. The role of clinical indices such as the Harvey-Bradshaw index (HBI) and surrogate inflammatory markers such as C-reactive protein (CRP) and faecal calprotectin to indicate mucosal healing is unsettled. Studies on predictive markers for endoscopic outcome in CD treated with anti-tumour necrosis factor-α antibodies (anti-TNF) are also limited. Retrospective data on 71 infliximab-treated patients (Study I) and prospective data on 42 either adalimumab- or infliximab-treated patients (Study II) underwent analysis to identify features predicting one-year endoscopic outcome. Study III analyzed retrospective data on 60 inflammatory bowel disease patients, including 34 with CD, to assess the predictive role of calprotectin measured after anti-TNF induction. Study IV included prospective data on 210 endoscopies to assess the power of surrogate markers and clinical indices to detect mucosal healing. Among patients receiving anti-TNF as maintenance therapy, 12-month mucosal healing was significantly more common in those patients who had presented 3-month mucosal healing, than in those with endoscopically active disease at 3 months. A normal calprotectin after anti-TNF induction was associated with, although without statistical significance, one-year endoscopic remission. Calprotectin was superior to CRP and clinical indices in detecting mucosal healing. However, although calprotectin alone identified endoscopic remission with 84% sensitivity and 74% specificity, it was beaten, but not statistically significantly, by a new combined index based on calprotectin and the HBI. In anti-TNF-treated active luminal CD, endoscopic remission at 3 months is a predictor for maintenance of the endoscopic response at one year. In patients on anti-TNF therapy, a normal faecal calprotectin after anti-TNF induction is a predictor of sustained clinical remission. A score based on a combination of calprotectin and the HBI may function as a new tool for identifying endoscopic remission. For optimisation of anti-TNF therapy in active luminal CD in clinical practice, these results suggest an objective inflammatory activity assessment such as ileocolonoscopy or determination of faecal calprotectin, performed as early as 3 months after initiation of therapy.
  • Sipponen, Taina (Helsingin yliopisto, 2009)
    Background: The fecal neutrophil-derived proteins calprotectin and lactoferrin have proven useful surrogate markers of intestinal inflammation. The aim of this study was to compare fecal calprotectin and lactoferrin concentrations to clinically, endoscopically, and histologically assessed Crohn’s disease (CD) activity, and to explore the suitability of these proteins as surrogate markers of mucosal healing during anti-TNFα therapy. Furthermore, we studied changes in the number and expression of effector and regulatory T cells in bowel biopsy specimens during anti-TNFα therapy. Patients and methods: Adult CD patients referred for ileocolonoscopy (n=106 for 77 patients) for various reasons were recruited (Study I). Clinical disease activity was assessed with the Crohn’s disease activity index (CDAI) and endoscopic activity with both the Crohn’s disease index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD). Stool samples for measurements of calprotectin and lactoferrin, and blood samples for CRP were collected. For Study II, biopsy specimens were obtained from the ileum and the colon for histologic activity scoring. In prospective Study III, after baseline ileocolonoscopy, 15 patients received induction with anti-TNFα blocking agents and endoscopic, histologic, and fecal-marker responses to therapy were evaluated at 12 weeks. For detecting changes in the number and expression of effector and regulatory T cells, biopsy specimens were taken from the most severely diseased lesions in the ileum and the colon (Study IV). Results: Endoscopic scores correlated significantly with fecal calprotectin and lactoferrin (p<0.001). Both fecal markers were significantly lower in patients with endoscopically inactive than with active disease (p<0.001). In detecting endoscopically active disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for calprotectin ≥200 μg/g were 70%, 92%, 94%, and 61%; for lactoferrin ≥10 μg/g they were 66%, 92%, 94%, and 59%. Accordingly, the sensitivity, specificity, PPV, and NPV for CRP >5 mg/l were 48%, 91%, 91%, and 48%. Fecal markers were significantly higher in active colonic (both p<0.001) or ileocolonic (calprotectin p=0.028, lactoferrin p=0.004) than in ileal disease. In ileocolonic or colonic disease, colon histology score correlated significantly with fecal calprotectin (r=0.563) and lactoferrin (r=0.543). In patients receiving anti-TNFα therapy, median fecal calprotectin decreased from 1173 μg/g (range 88-15326) to 130 μg/g (13-1419) and lactoferrin from 105.0 μg/g (4.2-1258.9) to 2.7 μg/g (0.0-228.5), both p=0.001. The relation of ileal IL-17+ cells to CD4+ cells decreased significantly during anti-TNF treatment (p=0.047). The relation of IL-17+ cells to Foxp3+ cells was higher in the patients’ baseline specimens than in their post-treatment specimens (p=0.038). Conclusions: For evaluation of CD activity, based on endoscopic findings, more sensitive surrogate markers than CDAI and CRP were fecal calprotectin and lactoferrin. Fecal calprotectin and lactoferrin were significantly higher in endoscopically active disease than in endoscopic remission. In both ileocolonic and colonic disease, fecal markers correlated closely with histologic disease activity. In CD, these neutrophil-derived proteins thus seem to be useful surrogate markers of endoscopic activity. During anti-TNFα therapy, fecal calprotectin and lactoferrin decreased significantly. The anti-TNFα treatment was also reflected in a decreased IL-17/Foxp3 cell ratio, which may indicate improved balance between effector and regulatory T cells with treatment.