Interleukin 6, osteoprotegerin, sRANKL and bone metabolism in inflammatory bowel diseases.

BACKGROUND: Cytokines are mediators of inflammatory processes in the course of inflammatory bowel disease (IBD) and participate in the bone metabolism. Interleukin 6 (IL-6) initiates osteoclastogenesis by modulating the activity of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin. OBJECTIVES: The aim of the study was to evaluate bone mineral density (BMD) by densitometry and the concentration of interleukin 6, osteoprotegerin (OPG) and sRANKL protein (sRANKL) by ELISA in patients with IBD in relation to the control group; to assess the relationship between IL-6, OPG, sRANKL and BMD; and to assess the impact of disease duration and number hospitalization on BMD. MATERIAL AND METHODS: The studied group included 37 patients with Crohn's disease (I - CD), 37 patients with ulcerative colitis (II - UC) and 37 healthy subjects - control group (III - CG). RESULTS: The prevalence of osteoporosis and osteopenia was as follows: in I - CD, 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, and in II - UC, 2.7% and 37.84% in L2-L4; 2.7%, and 29.73% in the femoral neck. The concentration of IL-6 correlated negatively with T-scores in the neck for the whole group, and in group I - CD, there was a significant positive correlation between serum OPG and IL-6. CONCLUSIONS: The incidence of osteopenia and osteoporosis in patients with IBD is high and increases with the duration of the disease and the number of hospitalizations. Patients with CD are at a higher risk of skeletal pathology than patients with UC. IL-6 can modulate bone mineral density in the femoral neck especially in the course of CD.

Trefoil factor-3 is not a useful marker of mucosal healing in Crohn's disease treated with anti-TNF-α antibodies.

AIM: To evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn's disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies. METHODS: Serum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn's disease (SES-CD). RESULTS: SES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD. CONCLUSION: Serum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.

Update on the mechanisms of action of anti­TNF-α antibodies and their clinical implications in inflammatory bowel disease.

The mechanisms of action of antitumor necrosis factor α (anti-TNF-α) antibodies in the therapy of inflammatory bowel disease (IBD) are not completely understood. Binding of antibodies to transmembrane TNF-α seems to be crucial for the induction of several cellular responses, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and reverse signaling. However, these processes alone do not fully explain the diversity of responses to anti-TNF-α therapy seen in different patients. Thus, the present review aimed to discuss the current role of anti-TNF-α antibodies in treatment algorithms for IBD as well as the current knowledge on the mechanisms of action of these antibodies, particularly the less well known aspects of anti-TNF-α blockade. We also discussed a complex role of particular macrophage subpopulations, T regulatory cells, and intestinal endothelial cells, as well as presented new data on the clinical relevance of anti-inflammatory responses attributed to the Fc region of anti-TNF-α antibodies.

Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn's disease naive to anti-TNF agents.

INTRODUCTION: Objective assessment of Crohn's disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. AIM: To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment. MATERIAL AND METHODS: Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically. RESULTS: The median time of follow-up was 29 months (interquartile range - IQR: 14-46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35-97%) sensitivity and 72% (IQR: 46-90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing). CONCLUSIONS: Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.

Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease.

Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn's disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases.

[The use of methotrexate in an inflammatory bowel diseases based on the review of the current literature].

M ethotrexate (MTX) as an immunomodulatory drug has numerous applications in autoimmune diseases. Autoimmune patomechanism is one of the factors responsible for development of inflammatory bowel diseases (IBD). MTX is an alternative therapy in the treatment of IBD. Over the past several years clinical trials has confirmed the efficacy of MTX in the treatment of Crohn's disease (CD). Data concerning use of MTX in ulcerative colitis (UC) are not as numerous as in the CD. Currently, MTX is recommended for the induction treatment and maintenance therapy in CD patients, especially in steroid-dependent patients, disease refractory to corticosteroids, no improvement after treatment with azathioprine and 6-mercaptopurine, or in case of intolerance to these drugs. Preferred route of administration in the treatment of CD is parenteral supply. Contraception is indicated during MTX treatment since it's teratogenic.

An increase in serum tumour necrosis factor-α during anti-tumour necrosis factor-α therapy for Crohn's disease - A paradox or a predictive index?

BACKGROUND: Soluble tumour necrosis factor-α (sTNF-α) has been reported to increase in the course of anti-TNF-α therapy for rheumatoid and skin diseases. AIMS: To assess changes in sTNF-α and clinical efficacy of anti-TNF-α agents in Crohn's disease (CD). METHODS: Sixty-four patients on infliximab or adalimumab were analyzed. Clinical outcomes were assessed by using CD Activity Index after the induction therapy and at week 52. sTNF-α was measured before and after the induction therapy with high-sensitivity immunoassay. RESULTS: In the majority of patients, sTNF-α increased significantly. Those with the greatest increase were more likely to experience long-term response, were more often treated with infliximab, had less frequently isolated small bowel CD, and tended to have sTNF-α levels at baseline that correlated with C-reactive protein. CONCLUSIONS: Neutralization of sTNF-α does not seem to be critical for the efficacy of anti-TNF-α therapy in CD. Paradoxically - an increase in sTNF-α may reflect an ongoing process that is beneficial for the clinical outcome.

The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn's disease patients in relation to mucosal healing.

INTRODUCTION: Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn's disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients. MATERIAL AND METHODS: Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel. RESULTS: The expression of CD31 and VEGF decreased significantly after the anti-TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5). CONCLUSIONS: We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD.

Osteoprotegerin, s-RANKL, and selected interleukins in the pathology of bone metabolism in patients with Crohn's disease.

INTRODUCTION: Crohn's disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known. AIM: Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD. MATERIAL AND METHODS: Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2-L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1ß, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected. RESULTS: The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1ß concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2-L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2-L4. CONCLUSIONS: The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1ß, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG.

Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease.

Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD).

Osteoporosis in Gastrointestinal Diseases.

Secondary osteoporosis occurs as an isolated pathology or co-exists with types I and II osteoporosis. The gastroenterologist may come across osteoporosis or osteopenia in a patient with a gastrointestinal disease. This is often a young patient in whom investigations should be carried out and appropriate treatment initiated, aimed at preventing bone fractures and the formation of the best peak bone mass. Osteoporosis occurs in patients with the following conditions: Crohn's disease, ulcerative colitis, celiac disease, post gastrectomy patients, patients with short bowel syndrome, chronic hepatitis and cirrhosis, treated with steroids (steroid-induced osteoporosis) and patients using proton pump inhibitors chronically (state of achlorhydria). It is therefore necessary to approve a list of risk factors of secondary osteoporosis, the presence of which would be an indication for screening for osteoporosis, including a DXA study and the development of a separate algorithm for the therapeutic management of secondary osteoporosis accompanying gastrointestinal diseases, especially in premenopausal young women and young men, because there are currently no registered drugs with proven antifracture activity for this group of patients.

Applicability of endoscopic indices in the determination of disease activity in patients with ulcerative colitis.

OBJECTIVE: The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index. METHODS: A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations. RESULTS AND CONCLUSION: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC.

Expression of cagA, virB/D Complex and/or vacA Genes in Helicobacter pylori Strains Originating from Patients with Gastric Diseases.

In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, virD4) and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains), multifocal atrophic gastritis-MAG (group 2) and gastric adenocarcinoma-GC (group 3). Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1) high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains). In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes.

Diagnostic importance of faecal markers in long-term monitoring of anti-TNF-α therapy in primary responders with Crohn's disease.

INTRODUCTION: Monitoring the response to biological treatment in Crohn's disease (CD) is a very important element of the therapeutic optimisation. AIM: To evaluate the usefulness of measuring calprotectin, lactoferrin, and myeloperoxidase in stool as markers of long-term clinical and endoscopic response to anti-tumour necrosis factor α (anti-TNF) treatment in CD. MATERIAL AND METHODS: The studied group consisted of 35 CD patients treated with anti-TNF-α antibodies. Clinical activity was evaluated using Crohn's Disease Activity Index (CDAI), and the exacerbation of endoscopic changes was evaluated using a Simple Endoscopic Score for Crohn's Disease (SES-CD). The concentration of calprotectin, lactoferrin, and myeloperoxidase was measured using the ELISA method. All measurements were performed three times - before, after 3 months, and after a year of therapy. RESULTS: During anti-TNF treatment the concentrations of all measured faecal markers decreased significantly in relation to baseline values. We observed a significant correlation at all time-points: before the therapy, after 3 months, and 12 months after starting the therapy, between the concentration of calprotectin and SES-CD, calprotectin and CDAI, as well as between lactoferrin and SES-CD, and lactoferrin and CDAI. Myeloperoxidase correlated with both SES-CD and CDAI only after 1 year of treatment. CONCLUSIONS: Faecal calprotectin and lactoferrin are valuable markers of clinical and endoscopic activity of CD in patients treated with anti-TNF antibodies. They are useful in monitoring the response to treatment. The usefulness of myeloperoxidase in this respect remains controversial.

The Participation of p53 and bcl-2 Proteins in Gastric Carcinomas Associated with Helicobacterpylori and/or Epstein-Barr Virus (EBV).

In the presented studies p53 and bcl-2 proteins expression were evaluated in samples of gastric carcinomas in patients with Helicobacter pylori or EBV or without H. pylori/EBV infection. The studies were conducted on 64 adult patients with gastric adenocarcinomas: 16 patients with H. pylori (cagA+)-positivity (group 1), 14 with EBV-positive tumours (group 2), 12 with H. pylori/EBV-positive tumours (group 3) and 22 patients with H. pylori/EBV-negative tumours (group 4). H. pylori presence in gastric tumour specimens was detected using Giemsa staining and bacterial culture technique. Moreover, cagA gene was detected using PCR. EBV infection was detected based on EBER presence in the tissue by RNA in situ hybridization. Expressions of p53 and bcl-2 proteins were analysed using immunohistochemistry. Expression of p53 was noted in 14 (84%) patients from group 1, 8 (57%) patients from group 2, 7 (58%) patients from group 3, and 19 (86%) patients from group 4, whereas expression of bcl-2 was noted in 12 (75%) patients from group 1, in 10 (71%) patients from group 2, 9 (75%) patients from group 3, and 6 (27%) patients from group 4. The obtained results allow the conclusion, that H. pylori (cagA+)-associated development of the gastric adenocarcinoma is determined by abnormalities in the p53 protein function and overexpression of anti-apoptotic bcl-2 protein, whereas EBV-associated adenocarcinomas seem to be related with apoptosis resistance associated with bcl-2 overexpression.

New pharmaceuticals in inflammatory bowel disease.

This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment.

The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases.

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

Evaluation of antimicrobial resistance of Helicobacter pylori in the last 15 years in West Poland.

Increasing resistance to drugs represents a serious problem in treatment of infections with Helicobacter pylori, providing cause of frequent therapeutic failures. Present study aimed at analysis of changes in resistance of H. pylori to antibiotics in West Poland within the recent 15 years. 108 strains of H. pylori were analysed, isolated from gastric mucosa of adult patients. Group 1 involved 66 strains isolated in years of 1998/1999. Group 2 comprised 42 isolates obtained in years of 2013/2014. Susceptibility to amoxicillin (AMX), clarithromycin (CL), tetracycline (TC) and metronidazole (MTZ) was determined by E-test (AB Biodisc). All strains on both studied groups were susceptible to AMX. In group 1 all strains proved to be susceptible to TC, while 9% and 36% of tested strains were resistant to CL and MTZ, respectively. By contrast, in group 2, 31% and 83% of strains were resistant to CL and MTZ, respectively. In parallel, 14% strains were found to be resistant to TC (according to EUCAST interpretations). In West Poland, within recent 15 years a dramatic increase was noted in H. pylori strains resistant to metronidazole. In parallel, a significant increase was noted in proportion of strains resistant to clarithromycin.

Association of serum VEGF with clinical response to anti-TNFα therapy for Crohn's disease.

Down-regulation of immune-mediated angiogenesis seems to be an important mechanism in anti-tumor necrosis factor α (anti-TNFα) therapy for Crohn's disease (CD). However, it remains to be established whether the baseline pro-angiogenic activity as reflected by the level of vascular endothelial growth factor (VEGF) could be of predictive value for successful clinical outcome of such treatment. Here, the levels of serum VEGF and other crucial angiogenesis-regulating peptides were assessed before and after induction anti-TNFα therapy in CD patients, and in age- and sex-matched healthy controls. Clinical, endoscopic, and biochemical activity of CD was estimated in parallel. CD patients were divided into two subgroups, depending on baseline VEGF levels: a "low-VEGF" subgroup with VEGF levels similar to those detected in healthy people, and a "high-VEGF" subgroup with VEGF levels significantly increased. VEGF levels were found to significantly correlate with CD clinical activity. Compared to the "low-VEGF" subgroup, the reduction in CD clinical activity as assessed by Crohn's Disease Activity Index was significantly greater in "high-VEGF" patients both in absolute numbers, and as a percentage of pre-treatment values. Accordingly, the fraction of patients who did not respond adequately to treatment was significantly greater in the "low-VEGF" group. These data indicate that VEGF may serve as an additional marker of CD activity and that baseline VEGF levels can be helpful in predicting the efficacy of anti-TNFα therapy.

The diagnostic usefulness of fecal lactoferrin in the assessment of Crohn's disease activity.

BACKGROUND: Diagnosis and monitoring of Crohn's disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce. AIMS: To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity. METHODS: The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohn's Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores. RESULTS: Median FL concentration was 84.14 (IQR: 36.4-302.9) µg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 µg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%. CONCLUSIONS: FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD.