Fecal Calprotectin In Combination With Plasma Markers In Evaluation Of Disease Activity In Patients With Ulcerative Colitis

Objectives: Ulcerative colitis(UC)is a chronic colorectal inflammatory disease characterized by a tendency of remissions and relapses alternatively.Clinically,mucosal healing is the main therapeutic goal for patients with UC and assessment of disease activity is repeatedly required.Colonoscopy and histopathological examinations are the main methods to assess the disease activity in UC.However,colonoscopy is an invasive procedure,limiting its clinical application.Disease severity scoring systems,such as modified Mayo score and UCEIS,cannot satisfy the need of assessment accuracy due to their strong subjectivity.Serum markers such as CRP and ESR have the advantages of fastness and convenience,but they lack high sensitivity and specificity.Fecal calprotectin(FC)is a reliable marker for UC,which can distinguish inflammatory bowel disease from irritable bowel syndrome,assess the disease activity of inflammatory bowel disease,and guide clinical decision-making.The aim of this study was to explore the clinical value of fecal calprotectin in combination with plasma markers in evaluation of disease activity in patients with ulcerative colitis.Methods: A total of 64 UC patients from the IBD center of the First Affiliated Hospital of Dalian Medical University from January 2019 to November 2020 were enrolled in this study.UC patients were divided into clinical remission,clinical mild and moderate to severe group according to the modified Mayo score and endoscopic remission and endoscopic active group according to the UCEIS,respectively.The differences of FC,CRP,platelet count,hemoglobin,ESR,serum albumin,d-dimer,interleukin-6,interleukin-8,and tumor necrosis factor-α were analyzed between the groups,and ROC curve was drawn to obtain AUC for evaluation of efficiency.According to the best cut-off value of each index,the predicted probability of the combination of the indexes were obtained through binary logistic regression analysis,which were used to drawn the ROC curve and to analyze the evaluation value of the combination of the indexes.Results:1.General data64 patients with UC were included.There were 35 male and 29 female patients,the average age of whom was 49.00±16.54 years and the average course of disease was52.42±71.47 months.According to Montreal classification,3 cases(4.70%)were E1 rectal type,23 cases(35.90%)were E2 left colon type,and 38 cases(59.40%)were E3 extensive colon type.A total of 61 cases completed colonoscopy,among whom 6 cases(9.80%)were in the clinical remission group,16 cases(26.20%)were in the mild group,39 cases(64.00%)were in the moderate to severe group.7 cases were in the endoscopic remission group(11.50%),54 cases(88.50%)were in the endoscopic active group.2.Comparison of indexes between clinical mild and moderate to severe groupThe values of FC,ESR,CRP,IL-6 and d-dimer in the clinical mild group were significantly lower than those in the moderate to severe group(P<0.05).The value of albumin in mild group was significantly higher than that in the moderate to severe group(P<0.05).There was no significant difference in platelet count,hemoglobin,interleukin-8,and tumor necrosis factor-α between the two groups(P>0.05).3.Comparison of indexes between endoscopic remission and active groupThe values of FC,IL-6,IL-8,and d-dimer in the endoscopic remission group were significantly lower than those in the endoscopic active group,and the difference between the two groups was statistically significant(P<0.05).The value of albumin in the endoscopic remission group was significant higher than in the endoscopic active group(P<0.05).No significant difference was found in CRP,platelet count,hemoglobin,ESR,and tumor necrosis factor-α between the two groups(P>0.05).4.Evaluation of clinical activityThe FC cut-off value between mild and moderate to severe activity was 70.82ug/g with a sensitivity of 94.90% and specificity of 56.30%,respectively(AUC 0.731).The CRP cut-off value between mild and moderate to severe activity was 3.25pg/ml with a sensitivity of 59.50% and specificity of 75.00%,respectively(AUC 0.742).The IL-6cut-off value between mild and moderate to severe activity was 4.38pg/ml with a sensitivity of 81.30% and specificity of 71.30%,respectively(AUC 0.781).The albumin cut-off value between mild and moderate to severe activity was 38.60g/L with a sensitivity of 56.40%and specificity of 87.50%,respectively(AUC 0.79).The ESR cut-off value between mild and moderate to severe activity was 15.00mm/h with a sensitivity of 65.80% and specificity of 75.00%,respectively(AUC 0.72).The d-dimer cut-off value between mild and moderate to severe activity was 285.00mg/L with a sensitivity of 83.30% and specificity of 53.30%,respectively(AUC 0.718).5.Evaluation of endoscopic activityThe FC cut-off value between endoscopic remission and active group was 39.87ug/g with a sensitivity of 88.95% and specificity of 85.70%,respectively(AUC 0.944).The IL-6cut-off value between endoscopic remission and active group was 2.79pg/ml with a sensitivity of 80.40% and specificity of 83.30%,respectively(AUC 0.897).The IL-8cut-off value between endoscopic remission and active group was 63.25ug/g with a sensitivity of 77.50% and specificity of 83.30%,respectively(AUC 0.846).The d-dimer cut-off value between endoscopic remission and active group was 285.00mg/L with a sensitivity of 74.50% and specificity of 83.30%,respectively(AUC 0.775).6.Fecal calprotectin in combination with plasma markers evaluating disease activityIn assessing clinical activity,the combination of FC+ESR+albumin+d-dimer achieved a maximum of AUC of 0.919,with a sensitivity of 80.60% and specificity of 86.70%,respectively.In assessing endoscopic activity,the combination of FC+IL-6+d-dimer achieved a maximum of AUC of 0.972,with a sensitivity of 95.90% and specificity of80.00%,respectively.Conclusion: The combination of fecal calprotectin with serum markers(ESR,albumin and d-dimer)shows a high efficiency and value in evaluating clinical activity in patients with ulcerative colitis,and the combination of fecal calprotectin with serum markers(IL-6 and d-dimer)shows a high efficiency and value in evaluating endoscopic activity in patients with ulcerative colitis.