Relevance of fecal calprotectin and lactoferrin in the post-operative management of inflammatory bowel diseases

Table 1 Studies evaluating fecal calprotectin and lactoferrin in operated Crohn’s disease patients

Ref.	FC/FL	Method	No. of patients	Aim	Best cut-off	Sens %	Spec %	Main findings
Scarpa et al[17]	FC and FL	ELISA	63 (22 endoscopy)	Role as marker of intestinal inflammation after ileocolonic resection	/	/	/	High FC and FL levels at long-term follow-up after resection even in case of clinical remission Correlation between FL and CRP Higher levels of FL in case of clinical recurrence
Ruffolo et al[18]	FL	ELISA (IBD-scan)	36	Correlation with systemic inflammation and prognostic value in terms of need of surgery for recurrence	/	/	/	FL as expression of subclinical intestinal inflammation (through IL6-CRP cascade)
Lamb et al[19]	FC and FL	ELISA (PhiCal) ELISA (IBD-Scan)	13 (prospective cohort) 104 (cross-sectional cohort; 43 endoscopy)	Evaluation of the course of FL and FC after ileocaecal resection. Identification of postoperative recurrence; Correlation between FC and FL	/	/	/	Prospective cohort: Normalization of fecal markers by 2 mo after surgery in uncomplicated patients Cross-sectional cohort: Significant correlation between FC and FL Significant correlation of fecal markers with HBI No significant difference between the FC and FL values in those with endoscopic recurrence and those without
Yamamoto et al[20]	FC and FL	ELISA (Cell Science) and Colloidal Gold Agglutination reagent (Auto Lf-Plus, respectively)	20	Evaluation of the relationship between endoscopic activity and FC/FL Assessment of Fc and FL predictive value for future clinical recurrence	FC 170 mg/g FL 140 mg/g (for prediction of clinical relapse)	83 67	93 71	Significant correlation between FC and FL Correlation with endoscopic activity Ability to predict clinical post-operative recurrence
Orlando et al[21]	FC	ELISA	50 (39 endoscopy)	Evaluation of the one year postsurgical endoscopic recurrence	200 mg/L	63	75	FC > 200 mg can be an indication to colonoscopy in patients with negative ultrasound in order to detect early recurrence
Lasson et al[22]	FC	ELISA (Buhlmann)	30	Correlation of FC with the endoscopic findings one year after ileocaecal resection Evaluation of the variation of FC in individual patients during 6 mo prior to the ileocolonoscopy	/	/	/	No difference in the concentrations of FC between patients in endoscopic remission and patients with recurrence one year after ileocaecal resection Significant variability of FC concentrations over time
Wright et al[25]	FC	ELISA (fCAL, Buhlmann)	135 (319 fecal samples)	To assess whether monitoring FC can substitute endoscopy and be used as surrogate marker of recurrent post-operative disease	100 μg/g	89	58	FC correlated with the presence of recurrent disease at endoscopy and with endoscopic severity FC has sufficient sensitivity and negative predictive values to monitor for recurrence FC can be used to monitor response to treatment after detection of recurrence FC has better diagnostic performance than CRP and clinical index of activity
Lobaton et al[27]	FC	ELISA (Buhlmann) FC-QPOCT (Quantum Blue)	115 (29 resected)	To evaluate the performance of a new rapid test for FC in predicting endoscopic remission (in both operated and non-operated CD patients)	283 μg/g	67	72	Significant correlation between ELISA and rapid test FC was able to discriminate between the presence or absence of endoscopic recurrence, but not distinguish different levels of severity

CD: Crohn’s disease; CRP: C-reactive protein; ELISA: Enzyme-linked immunoassay; FC: Fecal calprotectin; FL: Fecal lactoferrin; HBI: Harvey Bradshaw Index; Sens: Sensitivity; Spec: Specificity.

Table 2 Studies evaluating fecal calprotectin and lactoferrin in operated ulcerative colitis patients

Ref.	FC/FL	Method	No. of patients (No. of patients with inflammation of the pouch) and type of disease	Aim	Best cut-off	Sens %	Spec %	Main findings
Thomas et al[39]	FC	ELISA	24 (9) UC and familial polyposis coli	Comparison between single and 24-h stool collections in patients with and without pouchitis (endoscopic, histologic and immunohistochemical indeces)	/	/	/	Mean first morning stool concentration correlated with 24-h collection Levels of FC were significantly higher in patients with pouchitis Correlation with % of mature granulocytes and activated macrophages
Johnson et al[40]	FC	ELISA (PhiCal)	54 (20) UC and familial polyposis coli	Differentiation between inflamed and noninflamed pouches Correlation with inflammation severity	92.5 μg/g	90%	76.50%	FC levels significantly higher in pouchitis (> 50 μg/g had higher endoscopic and histological scores) Correlation with endoscopic score (r = 0.605) and histological score (r = 0.708)
Pakarinen et al[41]	FC	ELISA (PhiCal)	32 (22) UC	Cross-sectional assessment of FC after proctocolectomy for pediatric onset UC	300 μg/g (for detection of recurrent pouchitis)	57%	92%	Higher levels of FC in patients with recurrent pouchitis, followed by those with a single episode and those without (832, 290, 71 μg/g respectively, P = 0.019) Correlation with neutrophilic infiltration and overall inflammatory activity in the distal ileum
Parsi et al[42]	FL	In-house test	60 (30) UC	Evaluate the usefulness of FL in symptomatic patients with IPAA	13 μg/mL	97%	92%	Higher levels in patients with inflammation of the pouch Not able to distinguish between pouchitis, cuffitis and CD Not able to distinguish between asymptomatic patients and those with irritable pouch syndrome Correlation with PDAI (better for endoscopic subscore)
Lim et al[43]	FL	Rapid immuno-chromatographic test	32 (11) Healthy controls and pouchitis patients	Diagnostic yield for pouchitis	/	100%	86%	Sensitive method for the non-invasive diagnosis of pouchitis
Scarpa et al[44]	FL	ELISA (IBD-scan)	32 UC	Evaluate the relationship between ileal-pouch microbiota and inflammatory parameters	/	/	/	Correlation with histological inflammation Correlation with mucosal ulcers, mucosal immune infiltration Inverse correlation with Eubacteriaceae spp., Burkholderiaceae spp and Moraxellaceae spp. counts
Yamamoto et al[45]	FC FL	ELISA (Cell Science) and Colloidal Gold Agglutinantion reagent (Auto Lf-Plus, respectively)	60 (10) UC	Evaluate the significance of consecutive monitoring of fecal markers for early diagnosis and prediction of pouchitis	56 μg/g	100%	84%	Elevation of FC and FL already 2 mo before the diagnosis of pouchitis
					50 μg/g	90%	86%	Correlation with PDAI score (correlation with endoscopic and histological subscores, but not with the clinical subscore) Correlation with response to therapy

CD: Crohn’s disease; CRP: C-reactive protein; ELISA: Enzyme-linked immunoassay; FC: Fecal calprotectin; FL: Fecal lactoferrin; PDAI: Pouch disease activity index; Sens: Sensitivity; Spec: Specificity; UC: Ulcerative colitis.