Faecal Calprotectin, Lactoferrin And M₂-Pyruvate Kinase In Severe Ulcerative Colitis: A Prospective Comparison Of Predicting Steroid Therapy Outcomes And Monitoring Response

BackgroundSevere ulcerative colitis （UC）, characterized by profuse bloody diarrhea along withevidence of systemic upset （fever, tachycardia, and weight loss）, represents a major causeof morbidity and mortality in inflammatory bowel disease. Approximately15%of patientswith UC will develop severe disease, requiring hospital admission and intensive medicaltherapy with high dose steroid therapy. Some data have demonstrated that30%-40%ofsevere attacks will fail to respond to medical therapy and require emergency colectomy. Itis clear however that delays in the timing of surgery result in higher patient mortality.Predicting response to steroid medical therapy in managing severe ulcerative colitis getsmore and more important. The most reliable prognostic models, Southerland andTruelove-witts criteria （all calculated using parameters available at presentation） have beenused in identifying patients at high risk of failed medical therapy and thereby requiringearly second-line therapy intervention. In these indices, however, endoscopic andhistological evaluation of disease activity are most important, both of which are either tooinvasive or complicated to be regularly and repeatedly used in severe UC patients. Theretherefore remains great need for reliable biomarkers to complement existing clinicalindices that identify patients who will fail first-line medical therapies and will enableinformed decision making at an early stage during the admission. Blood tests, includingC-reactive protein, erythrocyte sedimentation rate and albumin, are in common used, butthey have only modest accuracy in reflecting UC disease activity. Recent attention hasbeen directed toward the use of fecal markers as a more direct indicator of disease activityand severity. M₂-PK is the dimeric form of the enzyme which converts phosphoenolpyr-uvat to lactate in the last step of the glycolytic pathway, leading to ATP production. Thisdimeric form is over expressed in proliferating cells, reflecting increased metabolic needs. Calprotectin and lactoferrin are important protein in the cytosol of neutrophils. Faecalcalprotectin, lactoferrin and M₂-pyruvate kinase （M₂-PK） have been shown to reflect theseverity of mucosal inflammation, but few data exist on the utility of these faecal markersin predicting steroid therapy of severe UC. A foreign research has shown that M₂-pyruvatekinase may be a hopeful fecal marker in predicting steroid therapy outcome in childrensevere UC. In this prospective study, we aimed to assess, head-to-head, the predictivevalidity of three inflammatory faecal markers in a large cohort of people with acute severeUC treated with steroid.ObjectiveThe purpose of the study was to determine the role of fecal M₂-pyruvate kinase,calprotectin and lactoferrin in the prediction of relapses in severe ulcerative colitis treatedwith steroid.MethodsPatients include46cases of severe ulcerative colitis conformed by clinicalmanifestation, colonoscopy and histology in General hospital of Chinese PLA Jinanmilitary Commend. All patients received prednisolone as first-line treatment and providestool sample before and after treatment. Patients divided into two groups according toresponse of steroid therapy, that is steroid responders （n=26） and steroid nonresponders（n=20）. ELISA assay was used to measure the concentration of calprotectin, lactoferrin andM₂-pyruvate kinase in faecal. Compare the difference of three faecal marks between twogroups. CRP, ESR,ALB were also measured between the two groups.Results1.Concentration of M₂-PK was significantly higher in the group of steroidnonresponders compared group with the steroid responders group [594.50IU/ml（458.18-654.21） vs.214.90IU/ml（144.20-485.60）, P<0.05]; calprotectin had no significant differe-nce in steroid nonresponders group compared with the steroid responders group [62.10ng/g（50.60-88.60） vs.53.66ng/g（45.14-57.66）,P>0.05]; lactoferrin had no significant differencein steroid nonresponders group patients compared with the steroid responders group[333.01μg/g（217.50-552.10） vs.236.24μg/g（199.63-248.84）, P>0.05].2.The value of CRP was significantly higher in steroid nonresponders group comp-ared with the steroid responders group [47.00mg/L（21.00-67.50） vs.4.00mg/L（1.20-28.00）,P<0.05]; ESR had no significant difference in steroid nonresponders group comp-ared with the steroid responders group [29.00mm/h（15.25-40.00） vs.18.00mm/h （15.00-26.00）,P>0.05]; ALB had no significant difference in steroid nonresponders group compared with the steroid responders group [30.10g/L（25.58-37.60） vs.37.30g/L （32.80-40.00）, P>0.05].3.M₂-PK receiver operator characteristic curve analysis yielded an area under thecurve of0.907to predict outcome, cutoff point is301.55IU/ml; CRP receiver operatorcharacteristic curve analysis yielded an area under the curve of0.804to predict outcome.Conclusion1.M₂-PK may be a hopeful faecal biological marker in predicting the outcome ofsteroid treatment in severe ulcerative colitis, which was superior to serum markers in thisstudy;2.Faecal calprotectin and lactoferrin showed no advantage of predicting validty whencompared with M₂-PK.