Diagnostic Efficacy of Fecal Calprotectin in Inflammatory Bowel Disease: Systematic Literature Review

Introduction: Inflammatory bowel disease is a group of pathologies that include ulcerative colitis and Crohn's disease, which have similar manifestations. Currently, the diagnosis and monitoring of this disease rely mainly on endoscopic studies. Still, this method can hardly be applied to periodic disease monitoring as it is expensive, invasive, and not readily available. Fecal calprotectin is widely known, easy to use, and affordable, and it is currently the best-characterized biomarker for this pathology. Materials and methods: The research design is a systematic diagnostic test validation literature review. A search was conducted in different databases using the QUADAS-2 checklist to evaluate the methodological quality. Results: The initial search yielded 352,843 articles published chiefly in PubMed, followed by Scopus and Science Direct. After multiple filters, 221 papers were selected and wholly reviewed. They were evaluated with inclusion and exclusion criteria, with 18 articles being chosen. Conclusions: Fecal calprotectin is a reliable surrogate marker of endoscopic activity in IBD. However, there is a lack of consensus on delimiting a cut-off point and improving applicability and diagnostic accuracy. Colonoscopy remains the gold standard in all studies.

Introducción: La enfermedad inflamatoria intestinal es un conjunto de patologías entre las que están incluidas la colitis ulcerativa y la enfermedad de Crohn, las cuales tienen presentación similar. En la actualidad, el diagnóstico y seguimiento de dicha enfermedad se basa principalmente en estudios endoscópicos, pero este método difícilmente puede aplicarse a la monitorización periódica de la enfermedad al ser costoso, invasivo y con disponibilidad limitada. La calprotectina fecal cumple con ser ampliamente disponible, fácil de usar y de precio asequible, y actualmente es el biomarcador mejor caracterizado para el uso en esta patología. Metodología: Diseño de investigación tipo revisión sistemática de la literatura de validación de prueba diagnóstica. Se realizó una búsqueda en diferentes bases de datos y para la evaluación de la calidad metodológica se empleó la lista verificación QUADAS-2. Resultados: La búsqueda inicial para la selección de los artículos arrojó un total de 352.843 artículos publicados principalmente en PubMed seguido de Scopus y Science Direct. Después de múltiples filtros se logró elegir 221 artículos, los cuales se llevaron a revisión completa. Se valoraron con criterios de inclusión y exclusión, lo que determinó la elección final de 18 artículos. Conclusiones: La calprotectina fecal es un marcador sustituto fiable de la actividad endoscópica en la EII. Se evidencia la falta de consenso para delimitar un punto de corte y mejorar la aplicabilidad y la precisión diagnóstica. La colonoscopia sigue siendo en todos los estudios el estándar de oro.

Study on fecal calprotectin in predicting disease activity and mucosal healing in patients with small intestinal Crohn′s disease / 中华消化杂志

Objective:To explore the differences of fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) between colon and small intestinal Crohn′s disease, and their predictive values for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Methods:From January 2017 to January 2023, 64 patients with Crohn′s disease who underwent capsule endoscopy in the First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled, among them 28 patients had only small intestinal lesions (small intestine group) and 36 patients had lesions involving both small intestine and colon or only colon involvement (ileocolon group). The FC, CRP, and ESR levels of the two groups were detected and compared 15 days before capsule endoscopy examination. Wilcoxon rank-sum test was used for statistical analysis. Receiver operating characteristic curve analysis was used to evaluate the predictive value of FC, CRP, and ESR for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Results:The FC, CRP, and ESR levels of the small intestine group during the active phase of the disease were 1 689.00 μg/g (727.75 μg/g, 1 800.00 μg/g), 5.67 mg/L (1.00 mg/L, 17.01 mg/L), and 4.50 mm/1 h (2.00 mm/1 h, 11.00 mm/1 h), respectively; while FC, CRP, and ESR levels during the mucosal healing phase were 112.00 μg/g (46.50 μg/g, 130.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.62 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h), respectively. The FC, CRP, and ESR levels of the ileocolon group during the active phase of the disease were 1 800.00 μg/g (895.50 μg/g, 1 800.00 μg/g), 4.94 mg/L (3.10 mg/L, 14.80 mg/L), and 10.00 mm/1 h (2.00 mm/1 h, 27.75 mm/1 h), respectively, while FC, CRP, and ESR levels during the mucosal healing phase were 66.00 μg/g (32.50 μg/g, 97.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.55 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 4.50 mm/1 h), respectively. There were no statistically significant differences in FC, CRP, and ESR between the small intestine group and the ileocolon group during the active phase of the disease and mucosal healing phase (all P> 0.05). In the small intestine group, the levels of FC and CRP of patients during the active phase of the disease were 1 173.00 μg/g (312.00 μg/g, 1 800.00 μg/g) and 2.10 mg/1 L (1.00 mg/L, 16.00 mg/L), which were both higher than those of patients during the mucosal healing phase (112.00 μg/g (46.50 μg/g, 130.50 μg/g) and 1.00 mg/L (1.00 mg/L, 1.62 mg/L)), and the differences were statistically significant ( Z=-4.35 and-2.67, P<0.001 and =0.008). In the small intestine group, the level of ESR of patients during the active phase of the disease was 4.00 mm/1 h (2.00 mm/1 h, 16.00 mm/1 h), and there was no significant difference compared with that of patients during the mucosal healing phase (2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h)) ( P>0.05). When the cut-off level of FC was 188.50 μg/g, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 93.3%, 100.0%, and 0.964, respectively. When the cut-off value of CRP was 3.12 mg/L, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 46.7%, 92.3%, and 0.744, respectively. When the cut-off level of ESR was 10.00 mm/1 h, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 33.3%, 100.0%, and 0.654, respectively. There were no statistically significant differences in the area under the curve between the combinations of FC and CRP, FC and ESR, FC, CRP and ESR, and FC alone for predicting disease activity in patients with small intestinal Crohn′s disease (0.964, 0.959, and 0.959 vs. 0.964, all P> 0.05). There was a statistically significant difference in the area under the curve between the combination of CRP and ESR and FC alone in predicting disease activity in patients with small intestinal Crohn′s disease (0.708 vs. 0.964, Z=-2.57, P=0.010). Conclusions:There are no statistically significant differences in FC, CRP, and ESR between colon and small intestinal Crohn′s disease. FC has a high predictive value for disease activity and mucosal healing in patients with small intestinal Crohn′s disease and has certain clinical application value.

Can fecal calprotectin reflect your colonic status?

Background: Organic colonic manifestation may be difficult to be differentiated from functional one. Inflammatory bowel disease (IBD) is a common chronic inflammatory and destructive disease of the bowel wall. Chronic inflammation is associated with ulcerations, strictures, perforations, and it is a risk factor for dysplasia and cancer. To reduce these long-standing complications, IBD patients are in a continuous need for early diagnosis1. Markers, such as erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP), fecal calprotectin (FC) have been widely used as noninvasive parameters for IBD monitoring. We aimed, in this current study, to evaluate the value of fecal calprotectin and other noninvasive biomarkers in predicting abnormal histologic findings in patients undergoing colonoscopy.in addition to determine the cutoff value which predict IBD2. Methods: The present prospective study included 160 patients with complaint of colicky abdominal pain with frequent diarrhea associated with mucous and infrequent bleeding per rectum for more than 6 months. They presented partial improvement with medication and recurrence once stopping the treatment These patients had been recently diagnosed with IBD at many primary healthcare centers covering the areas of the Kafrelsheikh and Zagazik governorate in the North of Egyptian Nile delta. After complete history, clinical examination, and laboratory investigation, they were referred to the IBD clinic at Kafrelsheikh University Hospital for assessment and ileocolonoscopy with biopsies. Results: There was a wide spectrum of age of the studied patients, with mean age 40.12±7.88 (minimum 18 and maximum 56 years). Regarding gender, males represented 87.5% of the studied patients. Forty percent of the patients with colonic manifestation were smokers, 57% preferred a spicy diet, and the majority had low educational level (77.5%). Forty percent had obvious blood in stool, 55% had occult blood, and raised ESR CRP occurred in 32.5% and 50%, respectively. Fecal calprotectin cutoff was>159, with sensitivity 92.8% and specificity 97.5%. Conclusions: Biomarkers (FC, ESR, CRP) can be used as noninvasive parameters for the early diagnosis and prediction of organic colonic disease. Fecal calprotectin in the IBD group revealed significant area under the curve (AUC) values and cutoff> 159, with sensitivity 92.8% and specificity 97.5%. (AU)

Efficacy and safety of adalimumab in the treatment of Crohn′s disease / 中华消化杂志

Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.

Significance of fecal calprotectin and eosinophil-derived neurotoxin in non-IgE-mediated food allergy / 国际儿科学杂志

Non-IgE-mediated food allergy most often presents with gastrointestinal symptoms such as diarrhoea, mucus stools, bloody stools, reflux and vomiting a few hours to days after exposure to the allergenic food.The pathogenesis may be related to the activation of intestinal T lymphocytes to secrete pro-inflammatory cytokines such as TNF-α and IL-4 by food allergens, leading to migration of neutrophils and eosinophils into the intestinal lumen, causing an intestinal inflammatory response and increased intestinal permeability.There is no rapid and specific diagnostic method.The diagnosis is mainly based on clinical manifestations combined with food avoidance and oral food challenge.In recent years, fecal biomarkers have been widely used as specific indicators for determining intestinal inflammation as an aid to diagnosis and condition assessment of intestinal infections and inflammatory bowel diseases, but their application in gastrointestinal allergic diseases is rarely reported.In this paper, we will focus on the significance of fecal calprotectin, fecal eosinophil-derived neurotoxin in non-IgE-mediated food allergy.

Fecal calprotectin levels used as a noninvasive method for screening for chronic gastritis in pediatric patients. A descriptive study

ABSTRACT BACKGROUND: Gastritis consists of inflammation of the gastric mucosa and is one of the main causes of dyspeptic symptoms in children. OBJECTIVE: To investigate the presence of inflammation by evaluating fecal calprotectin (FC) in children diagnosed with chronic gastritis. DESIGN AND SETTING: Descriptive study in Pediatric Gastroenterology Department of Ondokuz Mayis University Hospital in Turkey. METHODS: Between January 2016 and July 2018, FC levels were compared retrospectively in children with chronic gastritis (histopathology-based diagnosis), patients with inflammatory bowel disease (IBD) and healthy children. RESULTS: A total of 67 chronic gastritis patients (61.2% girls) with a mean age of 13.09 ± 3.5 years were evaluated. The mean FC levels were 153.4 μg/g in the chronic gastritis group, 589.7 μg/g in the IBD group and 43.8 μg/g in the healthy group. These levels were higher in chronic gastritis patients than in healthy individuals (P = 0.001) and higher in IBD patients than in the other two groups (P < 0.001). The FC level in the patients with chronic active gastritis (156.3 μg/g) was higher than in those with chronic inactive gastritis (150.95 μg/g) (P = 0.011). Among the patients with chronic active gastritis, the FC level was significantly higher in Helicobacter pylori-positive individuals than in negative individuals (P = 0.031). CONCLUSION: We confirmed the association between increased FC and chronic gastritis. Elevated FC levels may be seen in patients with chronic active gastritis. In order to be able to use FC as a screening tool for chronic gastritis, further studies in a larger study group are needed.

The level and clinical value of fecal calprotectin in very low birth weight infants / 中国小儿急救医学

Objective:To understand the change trend and influencing factors of fecal calprotectin(FC) in very low birth weight(VLBW) infants, and to explore the application value of FC detection in the diagnosis of necrotizing enterocolitis(NEC) in VLBW infants.Methods:VLBW infants hospitalized in the neonatal department at Quanzhou Children′s Hospital from June 2018 to May 2019 were selected as research object for a prospective study.Fecal samples from the 1st, 7th, 14th, 21st, 28th and 35th days after birth and fecal samples from the acute and recovery stages of NEC were collected continuously.The content of FC was determined quantitatively by immunofluorescence assay.Results:(1) The FC level of non NEC VLBW infants from 1 to 35 days after birth was 143.5(47.8, 391.2) μg/g.Univariate analysis showed that the level of FC fluctuated with the postnatal age, the level of FC was the highest at 21 days, and then decreased.The level of FC increased significantly in formula feeding, premature rupture of membranes, neonatal sepsis, feeding intolerance and pregnant mothers without glucocorticoid before delivery( P< 0.05). (2) Multivariate covariance analysis showed that prenatal application of glucocorticoid( F=10.550, P=0.001), premature rupture of membranes( F=13.311, P<0.001), neonatal sepsis( F=8.001, P=0.005), feeding intolerance( F=4.751, P=0.030) and NEC( F=54.566, P<0.001) had significant effects on FC level.After controlling the effects of prenatal corticosteroid, premature rupture of membranes, neonatal sepsis and feeding intolerance, the levels of FC in NEC group and non-NEC group were 3 162.3(1 412.5-7 244.4)μg/g and 141.3(125.9-162.2)μg/g, respectively.In NEC group, the levels of FC in acute stage and recovery stage were 3 166.9(1 745.1, 6 806.4)μg/g and 130.9(97.4, 273.9)μg/g, respectively, with significant difference( t=10.304, P<0.001). While the levels of FC were 2 347.9(1 404.4, 5 893.4)μg/g in the mild NEC and 4 114.7(2 764.5, 9 208.4)μg/g in the moderate or severe NEC, respectively, with no significant difference( t=1.131, P=0.280). Conclusion:The levels of FC fluctuate with postnatal age and it is affected by multiple factors.FC maybe a useful marker for the diagnosis and evaluation of efficacy of NEC in VLBW infants.

Effects of Anchang Decoction on TLR 4/NF-κB Signaling Pathway and the Expression of Fecal Calprotectin in Rats with Ulcerative Colitis Induced by TNBS / 中国药房

OBJECTIVE：To st udy the effects of Anchang decoction on TLR 4/NF-κB signaling pathway and the expression of fecal calprotectin （FC）in TNBS-induced ulcerative colitis （UC）model rats . METHODS ：SD rats were randomly divided into blank group ，model group ，positive control group [Live Bifidobacterium capsules ，5 mL（containing Bifidobacterium 0.35 g）]， Anchang decoction low -dose，medium-dose and high-dose groups （1，5，10 mL，each milliliter is approximately equivalent to 0.11 g of total crude drug ），with 15 rats in each group. Other groups were given TNBS combined with ethanol enema to establish UC model rat ，except blank group was given normal saline. Two days after successful modeling ，blank group and model group were given normal saline 5 mL，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. After last medication ，HE staining was used to observe the pathological change of colon tissue in rats. Western blotting assay was used to detect the protein expression of TLR 4，TRAF6 and NF-κB in colon tissues of rats；Real-time fluorescent quantitative PCR was used to detect mRNA expression of TLR 4，TRAF6，TNF-α and NF-κB；ELISA assay was adopted to detect serum level of TNF-α，IL-6 and FC in stool samples. RESULTS ：Compared with blank group ，the colonic mucosa of model group was severely damaged，and the protein expression of TLR 4，TRAF6 and NF-κB，mRNA expression of TLR 4，TRAF6，TNF-α and NF-κb as well as serum levels of TNF-α，IL-6 and FC level in stool samples were increased significantly （P＜0.05）. Compared with model group，the pathological changes of colon tissue in rats were improved in different administration groups to different extents ，and above indexes were all decreased significantly （P＜0.05）. CONCLUSIONS ：Anchang decoction may relieve the inflammation of UC model rats by regulating the TLR 4/NF-κB signaling pathway and the expression of FC.

Niveles de calprotectina fecal en pacientes con anticuerpos anti-transglutaminasa positivos y pacientes con dieta libre de gluten / Fecal calprotectin levels in patients with positive anti-transglutaminase antibodies and patients on a gluten free diet / Niveis de calprotectina fecal em pacientes com anticorpos anti-transglutaminase positivos e pacientes com dieta livre de gluten

La calprotectina fecal se ha afianzado en los últimos años como un marcador útil de las patologías gastrointestinales. El objetivo de este estudio fue determinar los niveles de calprotectina fecal (CPF), interleuquina-6 (IL-6) y proteína C reactiva (PCR) en tres grupos de pacientes: con diagnóstico de novo de enfermedad celíaca, con diagnóstico previo y dieta libre de gluten (DLG) y un grupo control. Se colectaron muestras de 79 pacientes entre 18 y 65 años. A todos se les determinó CPF, IL-6 y PCR como marcadores de inflamación y anticuerpos anti-transglutaminasa IgA y anti-gliadinas desaminadas IgA e IgG como marcadores serológicos. Se encontraron valores significativamente incrementados de PCR en el grupo de novo (124,06 μg/g) comparados con el grupo con DLG (23,61 μg/g) y el grupo control (16,91 μg/g) respectivamente. No se encontraron diferencias entre el grupo con DLG y el negativo (control). Idéntico comportamiento se observó para IL-6 con valores en el grupo de novo de 2,39 μg/dL, 1,74 μg/dL en el grupo con DLG y 1,41 μg/dL en el control negativo. No se encontraron diferencias significativas en el análisis de resultados de PCR. Se encontró una excelente sensibilidad (98,0%) y especificidad (96,6%) en la capacidad de la CPF para diferenciar valores de anti-transglutaminasa IgA superiores o inferiores al punto de corte cuando se estimó el índice de Youden. Se podría considerar a la CPF como un posible marcador sensible para indicar inflamación intestinal de manera no invasiva en la enfermedad celíaca.

The determination of fecal calprotectin has been strengthened in recent years as a useful marker of gastrointestinal pathologies. The objective of this study was to determine the levels of fecal calprotectin (FCP), interleukin-6 (IL-6) and C-reactive protein (CRP) in three groups of patients: with de novo diagnosis of celiac disease, with previous diagnosis and gluten-free diet (GFD) and a control group. Samples were collected from 79 patients between 18 and 65 years old. In all cases, FCP, IL-6 and RCP were determined as markers of inflammation and anti-transglutaminase IgA and deaminated anti-gliadin IgA and IgG antibodies as serological markers. Significantly more increased FCP values were found in the de novo group (124.06 μg/g) than in the group with DLG (23.61 μg/g) and the control group (16.91 μg/g). No differences were found between the group with GFD and the negative. The same trend was observed for IL-6 with values in the de novo group of 2.39 μg/dL, 1.74 μg/dL in the group with gluten free diet and 1.41 μg/dL in the negative control. No significant differences were found in the analysis of RCP results. Excellent sensitivity (98.0%) and specificity (96.6%) were found in the capability of the FCP to differentiate anti-transglutaminase IgA values higher or lower than the cut-off point when the Youden index was estimated. The FCP could be considered as a possible sensitive marker to indicate intestinal inflammation in a non-invasive manner in celiac disease.

A calprotectina fecal se consolidou nos ultimos anos como um marcador util das patologias gastrointestinais. O objetivo deste estudo foi determinar os niveis de calprotectina fecal (CPF), interleucina-6 (IL-6) e proteina C-reativa (PCR) em tres grupos de pacientes; com diagnostico de novo de doenca celiaca, com diagnostico previo e dieta livre de gluten (DLG) e um grupo controle. Foram coletadas amostras de 79 pacientes entre 18 e 65 anos. Em todos os casos CPF, IL-6 e PCR foram determinadas como marcadores de inflamacao e anticorpos anti-transglutaminase IgA e anti-gliadinas desaminadas IgA e IgG como marcadores sorologicos. Valores significantemente mais altos de PCR foram detectados no grupo de novo (124,06 μg/g) comparados com o grupo com DLG (23,61 μg/g) e o grupo controle (16,91 μg/g) respectivamente. Nao foram encontradas diferencas entre o grupo com DLG e o negativo (controle). O mesmo comportamento foi observado para IL-6 com valores no grupo de novo de 2,39 μg/dL, 1,74 μg/dL no grupo com DLG e 1,41 μg/dL no controle negativo. Na analise de resultados da PCR nao foram encontradas diferencas significativas. Foram detectadas uma sensibilidade excelente (98,0%) e especificidade (96,6%) na habilidade da CPF para diferenciar valores de anti-transglutaminase IgA superiores ou inferiores ao ponto de corte quando o indice de Youden foi estimado. Poderia ser considerada a CPF como um possivel marcador sensivel para identificar inflamacao intestinal de forma nao invasiva na doenca celiaca.

Fecal Fungal Community Structure of Newly Diagnosed Patients With Crohn's Disease in Suzhou, Jiangsu Province / 胃肠病学

Background: The pathogenic mechanism of Crohn's disease (CD) is currently unclear. Previous studies have shown that intestinal microorganism plays an important role in the pathogenesis of CD. Aims: To study the fecal fungal community structure of CD patients in Suzhou, Jiangsu Province and to analyze the relationship between alterations in fugal community structure and disease status. Methods: The feces of 23 newly diagnosed CD patients and 18 healthy subjects in Suzhou, Jiangsu Province were collected. Fecal genomic DNA was extracted, and the ITS1 fragments were amplified by PCR for clone library construction. After sequencing on HiSeq platform, the species diversity of fecal samples and the species differences between different groups were analyzed based on OTUs. Furthermore, the correlations between the fungi with up-regulated abundance and inflammatory indicators (CRP, ESR, and fecal calprotectin) and CD activity index (CDAI) were analyzed. Results: The fungal species diversity in fecal samples was significantly reduced in CD patients compared with healthy subjects. From the levels of phylum, class, order, family, genus, and species, the fungi with up-regulated abundance in fecal samples of CD patients were Saccharomycetes, Saccharomycetales, Incertae_sedis, Candida and Candida albicans; the fungi newly emerged were Trichosporonales and Trichosporonaceae; Wallemiomycetes was down-regulated in abundance and Glomeromycota, Glomeromycetes, Glomeraceae, Lodderomyces, Candida intermedia, and Candida sp were absent. The abundance of Candida albicans in feces was positively correlated with the fecal calprotectin in CD patients (r=0.557, P=0.031). Conclusions: Compared with healthy subjects, the structure of intestinal fungal community in CD patients changed significantly. The species diversity was reduced and the abundance of opportunistic pathogenic fungi such as Candida albicans was increased and might be involved in the disease progression.

Correlation of Fecal Fusobacterium nucleatum With Fecal Calprotectin in Patients With Crohn's Disease / 胃肠病学

Background: Fusobacterium nucleatum (Fn) is a common resident of the human GI tract and has been recognized as an opportunistic pathogen implicated in inflammatory bowel disease (IBD). Few studies had focused on the quantitative analysis of Fn in IBD patients. Aims: To establish a novel absolute quantitative real-time PCR method for detection of Fn in fecal samples of Crohn's disease (CD) patients and to study the correlation between fecal Fn and the common inflammatory indicators of CD. Methods: Fecal samples of 57 CD patients and 41 healthy subjects from Suzhou Municipal Hospital were collected and the genomic DNA was extracted. NusG (transcription antitermination protein) of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 was constructed into pUC57 to form a standard plasmid. An absolute quantitative standard curve was built by detecting the gradient diluted standard plasmid via SYBR Green real-time PCR method. The sensitivity, specificity and stability of this novel method were assessed, and then the novel method was used to detect the abundance of Fn in fecal sample of CD patients and healthy controls. Correlations between fecal Fn and fecal calprotectin (FC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were analyzed. Results: The absolute quantitative real-time PCR method for the detection of fecal Fn established in this study was sensitive, specific and stable. The detection rate and mean abundance of fecal Fn were significantly higher in CD patients than in healthy controls (P=0.034; P=0.039). Fecal Fn abundance in CD patients was positively correlated with FC level (r=0.459, P=0.011). Conclusions: The absolute quantitative real-time PCR established in this study is a promising method for human fecal Fn detection. In Suzhou, Jiangsu Province, the detection rate and abundance of fecal Fn are significantly increased in CD patients. Fecal Fn abundance in CD patients is correlated with FC level, and may reflect the disease activity.

Does fecal calprotectin equally and accurately measure disease activity in small bowel and large bowel Crohn's disease?: a systematic review

Fecal calprotectin (FC) is a highly sensitive disease activity biomarker in inflammatory bowel disease. However, there are conflicting reports on whether the diagnostic accuracy in Crohn's disease is influenced by disease location. The aim of this study was to undertake a systematic review of the published literature. Relevant databases were searched from inception to November 8, 2016 for cohort and case control studies which had data on FC in patients with isolated small bowel (SB) and large bowel (LB) Crohn's disease. Reference standards for disease activity were endoscopy, magnetic resonance imaging, computed tomography or a combination of these. The QUADAS-2 research tool was used to assess the risk of bias. There were 5,619 records identified at initial search. The 2,098 duplicates were removed and 3,521 records screened. Sixty-one full text articles were assessed for eligibility and 16 studies were included in the final review with sensitivities and specificities per disease location available from 8 studies. Sensitivities of FC at SB and LB locations ranged from 42.9% to 100% and 66.7% to 100% respectively while corresponding specificities were 50% to 100% and 28.6% to 100% respectively. The sensitivities and specificities of FC to accurately measure disease activity in Crohn's disease at different disease locations are diverse and no firm conclusion can be made. Better studies need to be undertaken to categorically answer the effect of disease location on the diagnostic accuracy of FC.

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces

BACKGROUND/AIMS: Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. METHODS: Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. RESULTS: The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. CONCLUSIONS: The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC.

The role of fecal calprotectin in pediatric disease / 소아과

Fecal calprotectin (FC) is a calcium- and zinc-binding protein of the S100 family, mainly expressed by neutrophils and released during inflammation. FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to nonspecific colitis and necrotizing enterocolitis. This article summarizes the current literature on the use of FC in clinical practice.

Application and Value of Fecal Calprotectin in Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal disease, including Crohn's disease (CD) and ulcerative colitis (UC). Colonoscopy and histopathology are the main diagnostic methods of IBD. Fecal biomarkers, especially fecal calprotectin (FC), can reflect the intestinal inflammation and having the advantage of non-invasive and easy for repetition, and can be used in the diagnosis, treatment, monitoring recurrence and predicting prognosis of IBD. This article reviewed the application and value of FC in IBD.

Diagnostic Value of Noninvasive Biomarkers in Endoscopic Activity of Ulcerative Colitis / 胃肠病学

Background: Ulcerative colitis (UC) is characterized by a chronic intestinal inflammatory disease with relapsing-remitting course, therefore the evaluation of inflammatory activity is essential for defining reasonable therapy and predicting prognosis. Aims: To evaluate the diagnostic value of noninvasive biomarkers in assessing endoscopic activity of UC. Methods: A total of 56 patients with UC from August 2016 to March 2018 at Xiangyang Central Hospital were enrolled, and 25 patients with irritable bowel syndrome (IBS) were served as controls. Fecal calprotectin (FC) level was measured by ELISA. Clinical activity index (CAI) was assessed, and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined. Endoscopic activity was determined by Mayo score. Diagnostic value of noninvasive biomarkers in assessing endoscopic activity of UC was analyzed. Results: FC level was significantly higher in UC patients than in IBS patients (P<0.001). FC, CAI, CRP, ESR in active UC patients were significantly higher than those in remissive UC patients (P<0.001). Mayo score was correlated with FC (r=0.814), CAI (r=0.724), CRP (r=0.610), ESR (r=0.657) (P all <0.001). FC with a cutoff value of 200 μg/g had sensitivity of 92.3% and specificity of 94.1% for detecting endoscopic activity. Conclusions: Compared with CAI, CRP and ESR, FC can more effectively evaluate the endoscopic active inflammation in UC patients.

Calprotectina fecal para diagnóstico de patología orgánica de colon / Fecal Calprotectin for the diagnosis of colon organic pathology

OBJETIVO: determinar la sensibilidad y especificidad de la calprotectina fecal (CPF) y la prueba de sangre oculta en heces (SOH) para el diagnóstico de patología orgánica de colon. MÉTODOS: se realizó un estudio observacional que, incluyó de manera intencionada, 246 pacientes de ambos sexos atendidos en el Instituto Gastroenterológico Boliviano Japonés de Cochabamba, por dolor abdominal, diarrea crónica y pérdida de peso. Se les realizó laboratorios de calprotectina fecal y sangre oculta en heces, además de colonoscopia como estudio de control. RESULTADOS: se determinó que la calprotectina fecal tiene una sensibilidad de 86 %, y especificidad de 98 %, con una asociación de 0,54 y relación de 0,75 según los coeficientes de Pearson y Spearman respectivamente, en relación con la colonoscopía y el diagnóstico de patología orgánica de colon. La prueba de sangre oculta en heces presentó una sensibilidad de 79% pero una especificidad de 58%, la asociación y relación con el estudio de control fue mínima: 0,21 y 0,22 según los coeficientes de Pearson y Spearman. CONCLUSIONES: los resultados muestran que la calprotectina fecal presenta alta sensibilidad y especificidad para el diagnóstico de patología orgánica de colon. Los valores más altos se relacionaron con mayor lesión en la mucosa colónica.

OBJECTIVE: to determine the sensitivity and specificity of fecal calprotectin and fecal occult blood test (FOBT) for the diagnosis of organic colon pathology. METHODS: an observational study was made, which intentionally included 246 patients of both sexes seen at the Japanese Bolivian Gastroenterological Institute of Cochabamba, due to abdominal pain, chronic diarrhea and weight loss. We performed fecal calprotectin and fecal occult blood laboratories, as well as colonoscopy as a control study. RESULTS: it was determined that the fecal calprotectin has a sensitivity of 86%, and specificity of 98%, with an association of 0,54 and a ratio of 0,75 according to the Pearson and Spearman coefficients respectively, in relation to colonoscopy and the diagnosis of organic pathology of colon. The fecal occult blood test showed a sensitivity of 79% but a specificity of 58%, according to the association and relationship with the control minimum of 0,21 and 0,22 according to the Pearson and Spearman coefficients. CONCLUSIONS: The results show that fecal calprotectin presents high sensitivity and specificity for the diagnosis of organic colon pathology. Higher values were associated with greater lesion in the colonic mucosa.

Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis

BACKGROUND/AIMS: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. METHODS: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. RESULTS: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p<0.0001 vs r=0.30, p=0.054). CONCLUSIONS: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.

Experience of patients with inflammatory bowel disease in using a home fecal calprotectin test as an objective reported outcome for self-monitoring

BACKGROUND/AIMS: Fecal calprotectin (fC) level is a predictive marker of mucosal healing for patients with inflammatory bowel disease (IBD). Home fC tests are now available. We evaluated the performance of the smartphone-based IBDoc home testing system in patients with IBD and obtained their feedback as an objective patient-reported outcome. METHODS: This prospective study enrolled consecutive patients with IBD in clinical remission. fC in the same stool sample was assessed by using both the laboratory test (Quantum Blue calprotectin test) and home test (IBDoc). The correlation between the 2 tests was analyzed using the Pearson method. In addition, the patients were asked to fill a questionnaire based on their experience. RESULTS: Fifty-one patients with IBD (68 tests and 49 questionnaires) were included. The correlation between Quantum Blue test and IBDoc was good (r=0.776, P 70%) probability to use it for future monitoring if the price was acceptable. By using 250 μg/g as the cutoff, the agreement between home test and laboratory results was 80%, and by using 600 μg/g as the cutoff, the agreement increased to 92%. CONCLUSIONS: The correlation between the laboratory and home tests was good. Most patients found the home test to be feasible and easy to use and preferred it over laboratory test and endoscopy for monitoring. Therefore, the home test could be used as an objective patient-reported outcome.

Usefulness of fecal calprotectin by monoclonal antibody testing in adult Japanese with inflammatory bowel diseases: a prospective multicenter study

BACKGROUND/AIMS: Noninvasive objective monitoring is advantageous for optimizing treatment strategies in patients inflammatory bowel disease (IBD). Fecal calprotectin (FCP) is superior to traditional biomarkers in terms of assessing the activity in patients with IBD. However, there are the differences among several FCP assays in the dynamics of FCP. In this prospective multicenter trial, we investigated the usefulness of FCP measurements in adult Japanese patients with IBD by reliable enzyme immunoassay using a monoclonal antibody. METHODS: We assessed the relationship between FCP levels and disease or endoscopic activity in patients with ulcerative colitis (UC, n=64) or Crohn’s disease (CD, n=46) compared with healthy controls (HCs, n=64). RESULTS: FCP levels in UC patients strongly correlated with the Disease Activity Index (rs =0.676, P < 0.0001) and Mayo endoscopic subscore (MES; rs =0.677, P < 0.0001). FCP levels were significantly higher even in patients with inactive UC or CD compared with HCs (P=0.0068, P < 0.0001). The optimal cutoff value between MES 1 and 2 exhibited higher sensitivity (94.1%). FCP levels were significantly higher in active UC patients than in inactive patients (P < 0.001), except those with proctitis. The Crohn’s Disease Activity Index tended to correlate with the FCP level (rs =0.283, P=0.0565). CONCLUSIONS: Our testing method using a monoclonal antibody for FCP was well-validated and differentiated IBD patients from HCs. FCP may be a useful biomarker for objective assessment of disease activity in adult Japanese IBD patients, especially those with UC.