Precisión diagnóstica de la calprotectina fecal y la M2-piruvato quinasa en la detección de actividad endoscópica en la enfermedad de Crohn

Supervised by:
  1. Héctor Pallarés Manrique Director
  2. Carlos Ruiz Frutos Director

Defence university: Universidad de Huelva

Fecha de defensa: 07 July 2017

  1. Manuel Vaquero Abellán Chair
  2. Juan Gómez Salgado Secretary
  3. M. Castro Fernández Committee member

Type: Thesis


Backgrounds: The symptoms are not useful for accurately establishing endoscopic activity in Crohn’s disease. Fecal biomarkers are more accurate than serological tests to detect activity, although clinical applicability is limited because there is no consensus on the optimal cutoff point to establish the presence of endoscopic activity. This study analyzes whether fecal calprotectin (CF) and M2-pyruvate kinase (M2-PK) are good tools to detect endoscopic activity and generate highly accurate ranges to predict the state of activity and mucosal healing. Methods: The simple endoscopic score for Crohn's disease (SES-CD) and the Crohn's disease activity index (CDAI) was calculated for 71 patients diagnosed with Crohn's disease, determining levels of CF, M2-PK, C- reactive protein and erythrocyte sedimentation rate, and a precision analysis by estimating the ROC curve of the biomarkers and the CDAI with respect to the SES-CD, Binary logistic regression was classified according to endoscopic activity and a cut-off with specificity> 90% and LR + > 10 was sought as solid evidence to support the diagnostic hypothesis, and cut-off point with sensitivity> 90% and LR - < 0,1 to be able to reject this hypothesis. The Fagan nomogram was calculated to determine the probability of endoscopic activity or cure of the mucosa after obtaining the biomarker score and according to the presence or absence of clinical symptoms. Results; 71 patients were included, of whom 49 patients had endoscopic activity (69%). It was observed that there were significant differences between the mean levels of the biomarkers and CDAI score in the endoscopic activity group with respect to the group mucosal healing. ROC curves of biomarkers and CDAI with respect to the SES-CD showed that FC was the variable with higher area under the curve (0.917) followed by M2-PK (0.846). An optimal cutoff point for FC of 170 pg/g (sensitivity 77.5% and specificity 95.5%) to detect endoscopic activity, while for M2-PK was 4.5 U / ml (sensitivity 87.8% and specificity 81.8%). FC was the only variable that reached levels required to be able to generate ranges with high precision in the detection of mucosal healing and endoscopic activity. A FC cut-off of 170 pg/g (Sensitivity 77.6%, Specificity 95.5% and LR+ 17.06) predicted a high probability of endoscopic activity and a FC cut-off of 71 pg/g (Sensitivity 95.9%, Specificity 52.3% and LR- 0.08) predicted a high probability of mucosal healing. The prevalence of endoscopic activity was 69%, but if patients show FC > 170 pg/g they have a 97% probability of presenting endoscopic activity; and If they have FC <71 pg/g the probability to present mucosal cure would be 84%. Clinical symptoms modified the probability of predicting endoscopic activity (100% if clinical activity vs 89% if clinical remisión) or mucosal healing (75% if clinical activity vs 87% if clinical remisión), it was estimated that FC and CDAI, included in one model, had the highest degree of statistical significance in the hypothesis contrast, The model correctly classifies 85.9% of the sample and the proportion of SES-CD variability that is explained by this model Is acceptable between 49% and 68.9%. Conclusions: Fecal calprotectin and fecal M2-pyruvate kinase are more accurate than the clinical CDAI index, C-reaclive protein and erythrocyte sedimentation rate to establish the presence of inflammatory activity observed by ileocolonoscopy. Fecal calprotectin is a useful tool for generating highly accurate scores for predicting the state of endoscopic activity or mucosal healing in Crohn's disease patients. Although, it is necessary to contemplate the specific clinical context to interpret probabilities of presenting endoscopic activity or mucosal cure according to the level of fecal calprotectina.