Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings

Background Faecal calprotectin and lactoferrin increasingly serve as surrogate markers of disease activity in IBD. Data on the correlation of these markers with simple endoscopic score for Crohn’s disease (SES‐CD) and with histological findings are as yet limited. Aim To study the correlation of faecal calprotectin and lactoferrin with SES‐CD and histology. Methods  During 87 consecutive ileocolonoscopies, SES‐CD was calculated and biopsy specimens were obtained from the ileum, colon and rectum. Faecal calprotectin and lactoferrin were measured. Results In ileocolonic or colonic disease, both faecal calprotectin and lactoferrin correlated significantly with colon SES‐CD (P < 0.001) and colon histology (P < 0.001). In patients with normal calprotectin or lactoferrin levels, endoscopic and histology scores were significantly lower than in those with elevated concentrations (P < 0.001). In ileal CD, ileal SES‐CD correlated with histology (P < 0.001), but not with faecal calprotectin (P = 0.161) or lactoferrin (P = 0.448). Conclusion In ileocolonic and colonic disease, endoscopic score SES‐CD and histological findings correlated significantly with faecal calprotectin and lactoferrin. A normal faecal‐marker concentration was a reliable surrogate marker for endoscopically and histologically inactive CD. Ileal endoscopic score and histological findings failed, however, to correlate with faecal markers.     

Faecal lactoferrin – a novel test to differentiate between the irritable and inflamed bowel?

Aliment Pharmacol Ther 31 , 1365–1370

Summary

Background Distinguishing between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can be challenging. Aims To investigate the utility of faecal lactoferrin as a marker of inflammation in patients with IBD, IBS and controls. Methods Disease activity in IBD patients was assessed using the modified Harvey–Bradshaw Activity Index. Stool samples were analysed using an ELISA assay. Results We recruited 137 patients with IBS, 126 with ulcerative colitis (UC) and 104 with Crohn’s disease (CD), and 98 healthy volunteers. The median ± IQ lactoferrin concentration (μg/g faecal weight) was 0 ± 1.4 for IBS patients, 6.6 ± 42 for UC patients, 4 ± 12.7 for CD patients and 0.5 ± 2 for healthy controls. Lactoferrin levels were significantly higher in IBD patients compared with IBS/healthy controls (P < 0.001). The median lactoferrin concentrations were significantly higher in active UC & CD patients compared with inactive patients (P < 0.001 and P = 0.002 respectively). The sensitivity, specificity, positive and negative predictive values of lactoferrin in distinguishing active IBD from IBS/healthy controls were 67% and 96%, 87% and 86.8% respectively. Conclusions Lactoferrin is useful to differentiate between IBD and IBS, and can be used as an adjunct to blood parameters to determine IBD patients who have ongoing inflammation.     

Additional benefit of procalcitonin to C-reactive protein to assess disease activity and severity in Crohn's disease

Aliment Pharmacol Ther 2010; 32: 1135–1144

Summary

Background Serum procalcitonin level may reflect non‐infectious inflammation. Aim To assess the correlation of serum procalcitonin level with clinical, biological, endoscopic and radiological markers of disease activity in inflammatory bowel diseases (IBD), and to evaluate the additional diagnostic benefit of measuring serum procalcitonin level to that of C‐reactive protein (CRP) for disease activity appraisal. Methods We performed a prospective observational study. Spearman’s rank correlation and receiver operating characteristic analysis were used to evaluate correlation and diagnostic accuracy respectively. Results In Crohn’s disease (CD) (n = 30), serum procalcitonin level was strongly correlated with clinical, biological, endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level >0.14 μg/L demonstrated a high accuracy for detecting severe disease (Sensitivity = 100%; Specificity = 96%; AUROC = 0.963; P = 0.0001). The diagnostic accuracy of the ‘serum procalcitonin level‐CRP strategy’ (CRP >5 mg/L and serum procalcitonin level >0.05 μg/L) was significantly superior to that of CRP alone for diagnosing severe CD (AUROC = 0.783 vs. 0.674; P = 0.01). In ulcerative colitis (UC) (n = 27), serum procalcitonin level was correlated with CRP and with endoscopic and radiological disease activity markers. Conclusions In CD, the serum procalcitonin level was correlated with all disease activity markers and a cut‐off of 0.14 μg/L could distinguish severe forms of the disease. The ‘serum procalcitonin level‐CRP strategy’ was superior to CRP alone for diagnosing active or severe CD.     

Increased lymphatic vessel density and lymphangiogenesis in inflammatory bowel disease

Aliment Pharmacol Ther 2011; 34: 533–543

Summary

Background Involvement of the lymphatic system in inflammatory bowel disease (IBD) has been suggested. Aims To examine the density and distribution of lymphatic vessels (LV) within inflamed and non‐inflamed wall sections of IBD patients compared with controls, and to evaluate expression of major lymphangiogenic factors. Methods Ileal and colon specimens of 22 patients with Crohn’s disease (CD), 16 patients with ulcerative colitis (UC) and 11 controls were studied. Quantification of LV was performed using immunohistochemistry with podoplanin and D2‐40 antibodies on seven randomly selected fields. Mucosal expression of podoplanin and lymphangiogenic factor mRNA was measured using PCR. Results In CD patients, lymphatic density was significantly increased in non‐inflamed and inflamed ileal (P < 0.01 and P < 0.001) and colonic (P < 0.01 and P < 0.001) mucosa compared to controls. Podoplanin mRNA levels were similar in non‐inflamed mucosal areas and controls, whereas a four‐ and sixfold increase was seen in inflamed ileal and colonic areas (P < 0.05). In UC, lymphatic density increased fourfold in non‐inflamed (P < 0.001) and fivefold in inflamed colonic mucosa (P < 0.001) compared with controls. An increase in podoplanin mRNA levels was seen in both non‐inflamed and inflamed areas (P < 0.01) compared with controls. In CD and UC, lymphatics were found throughout the inflamed mucosa, including the upper half of the lamina propria. Expression of lymphangiogenic factors was similar in patients and controls. Conclusions Increased density of lymphatic vessels is a constant feature of IBD and is present in non‐inflamed areas. It is transmural in CD and confined to the mucosa in UC. Its origin remains unclear.     

Prediction of Crohn's disease relapse with faecal calprotectin in infliximab responders: a prospective study

Aliment Pharmacol Ther 2011; 34: 462–469

Summary

Background Faecal calprotectin is a reliable tool for predicting Crohn’s disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti‐TNF. Aim To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX). Methods From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5 mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C‐reactive protein (CRP) were measured at entry and at week 14 (w14). Results Sixty‐five patients (43W; median age: 30.4 years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty‐three of fifty (46%) experienced CD clinical relapse during the first year of follow‐up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150 μg/g respectively). When considering two suggested faecal calprotectin cut‐offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130 μg/g, respectively, and 43% and 57% for 250 μg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered. Conclusion In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn’s disease clinical relapse at 1 year.     

Chronic fatigue is associated with impaired health-related quality of life in inflammatory bowel disease

Aliment Pharmacol Ther 2011; 33: 106–114

Summary

Background Fatigue is reported to reduce health‐related quality of life (HRQOL) in chronic diseases. Studies on the importance of fatigue and its implications for the patient’s HRQOL in inflammatory bowel disease (IBD) remain scarce and need to be explored. Aim  To investigate the influence of chronic fatigue on both generic and disease‐specific HRQOL in IBD. Methods Patients in remission, with mild and moderate IBD completed the Fatigue Questionnaire, the Short‐Form 36 (SF‐36) and the Norwegian version of the Inflammatory Bowel Disease Questionnaire (N‐IBDQ). In addition, demographic and clinical variables were obtained. Results In total, 140 patients were included; the mean age of patients with chronic fatigue was 44.2 years (s.d. = 15.8), that of nonfatigued was 44.7 years (s.d. = 16.0). Ulcerative colitis (UC)/Crohn’s disease (CD) = 92/48. Chronic fatigue was associated, after controlling for covariates, with a reduction of HRQOL scores in 6/8 SF‐36 dimensions in UC and 5/8 dimensions in CD. In N‐IBDQ, chronic fatigue was associated with a reduction of HRQOL in four subdimensions and total score in CD and all dimensions in UC. Conclusions Fatigue is associated with reduction of HRQOL scores in IBD. The physical HRQOL domains are particularly affected. The impact of fatigue on disability, sick leave, school and work attendance has to be studied further.     

Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003-2006

Aliment Pharmacol Ther 2011; 34: 724–734

Summary

Background Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies. Aim To evaluate the pregnancy outcome in patients with IBD in a prospective European multicentre case‐control study. Methods Inflammatory bowel disease pregnant women from 12 European countries were enrolled between January 2003 and December 2006 and matched (1:1) to non‐IBD pregnant controls by age at conception and number of previous pregnancies. Data on pregnancy and newborn outcome, disease activity and therapy were prospectively collected every third month using a standard questionnaire. Logistic regression analysis with odds ratio was used for statistical analyses. P value < 0.05 was considered significant. Results A total of 332 pregnant women with IBD were included: 145 with Crohn’s disease (CD) and 187 with ulcerative colitis (UC). Median age (range) at conception was 31 years (15–40) in CD and 31 (19–42) in UC patients. No statistically significant differences in frequency of abortions, preterm deliveries, caesarean sections, congenital abnormalities and birth weight were observed comparing CD and UC women with their non‐IBD controls. In CD, older age was associated with congenital abnormalities and preterm delivery; smoking increased the risk of preterm delivery. For UC, older age and active disease were associated with low birth weight; while older age and combination therapy were risk factors for preterm delivery. Conclusion In this prospective case‐control study, women with either Crohn’s disease or ulcerative colitis have a similar pregnancy outcome when compared with a population of non‐inflammatory bowel disease pregnant women.     

Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease--a population-based study

Aliment Pharmacol Ther 2011; 34: 1217–1224

Summary

Background Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). Aim To compare phenotype, treatment and disease course in children (<15 years) and adults (≥18 years) with IBD. Methods Two population‐based cohorts comprising paediatric (2001–2006) and adult (2003–2004) patients from Copenhagen County and City were studied. Results Twenty children and 106 adults with ulcerative colitis (UC), and 29 children and 67 adults with Crohn′s disease (CD) were included. Median follow‐up time was 4.8 years (children) and 5.2 years (adults). Children with UC had more extensive disease compared to adult patients [14 (70%) vs. 20 (19%), P < 0.001]. The risks of starting systemic steroid treatment and AZA/MP were higher for paediatric UC patients compared to adult UC patients; hazard ratio (HR): 3.1 (95% CI: 1.8–5.3) and HR: 2.5 (1.3‐5‐9), respectively. Steroid dependency was more frequent in paediatric than in adult UC patients [9 (45%) vs. 9 (8%), P < 0.001]. Mild disease course was less frequent in children with UC compared to adult patients [7 (35%) vs. 76 (72%), P = 0.002]. Paediatric and adult CD patients did not differ regarding treatment or disease course. Cumulative 5‐year surgery rates for paediatric and adult patients were 5% and 9% for UC (N.S.) and 18% and 21% for CD (N.S.), respectively. Conclusions Paediatric UC patients had more extensive disease, were more often treated with systemic steroids and AZA, had a higher frequency of steroid dependency and a more severe disease course compared to adult UC patients. No differences were found when comparing paediatric and adult CD patients.     

Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases

Aliment Pharmacol Ther 2011; 34: 1173–1184

Summary

Background The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD. Aim To conduct a systematic review and meta‐analysis to examine these issues. Methods The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD. Results Twenty‐eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD) = 3.75 μmol/L; 95% CI, 2.23–5.26 μmol/L; P < 0.0001; reference ranges for plasma homocysteine level: 5–12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn’s disease (CD) (WMD = 0.41 μmol/L; 95% CI, −2.45 to 3.06 μmol/L; P = 0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR) = 4.65; 95% CI, 3.04–7.09; P < 0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR = 1.97; 95% CI, 0.83–4.67; P = 0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P = 0.006). Conclusions The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia–related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.

     

Review article: faecal transplantation therapy for gastrointestinal disease

Aliment Pharmacol Ther 2011; 34: 409–415

Summary

Background Evidence is emerging regarding the relationship between a dysbiosis of the human gut microbiota and a number of gastrointestinal diseases as well as diseases beyond the gut. Probiotics have been investigated in many gastrointestinal disease states, with variable and often modest outcomes. Faecal transplantation is an alternative approach to manipulate the gut microbiota. Aim To review the use of faecal transplantation therapy for the management of gastrointestinal disorders. Methods Available articles on faecal transplantation in the management of gastrointestinal disorders were identified using a Pubmed search and bibliographies of review articles on the subject were collated. Results A total of 239 patients who had undergone faecal transplantation were reported. Seventeen of 22 studies of faecal transplantation were in fulminant or refractory Clostridium difficile. Studies of faecal transplantation are heterogeneous regarding the patients, donors, screening, methods of administration and definition of response. Faecal transplantation for C. difficile has been demonstrated to be effective in 145/166 (87%) patients. Small numbers of patients are reported to have undergone successful faecal transplantation for irritable bowel syndrome and inflammatory bowel disease. Conclusions Faecal transplantation has been reported with good outcomes for fulminant and refractory C. difficile. No adverse effects of faecal transplantation have been reported. However, there are no level 1 data of faecal transplantation and reports to date may suffer from reporting bias of positive outcomes and under‐reporting of adverse effects. This therapy holds great promise, where a dysbiosis of the gut microbiota is responsible for disease and further studies are necessary to explore this potential.     

Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis

Background Intestinal microbiota manipulation, one of the pathogenetic components of inflammatory bowel disease (IBD), has become an attractive therapy for ulcerative colitis (UC). Aim To assess in children with active distal UC the effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and cytokine expression of rectal mucosa. Methods A total of 40 patients (median age: 7.2 years range 6–18) with mild to moderate UC were enrolled in a prospective, randomised, placebo‐controlled study. They received an enema solution containing 10¹⁰ CFU of L. reuteri ATCC 55730 or placebo for 8 weeks, in addition to oral mesalazine. Clinical endoscopic and histological scores as well as rectal mucosal expression levels of IL‐10, IL‐1β, TNFα and IL‐8 were evaluated at the beginning and at the end of the trial. Results Thirty‐one patients accomplished the trial (17 males, median age 13 year, range 7–18). Mayo score (including clinical and endoscopic features) decreased significantly in the L. reuteri group (3.2 ± 1.3 vs. 8.6 ± 0.8, P < 0.01) compared with placebo (7.1 ± 1.1 vs. 8.7 ± 0.7, NS); furthermore, histological score significantly decrease only in the L. reuteri group (0.6 ± 0.5 vs. 4.5 ± 0.6, P < 0.01) (placebo: 2.9 ± 0.8 vs. 4.6 ± 0.6, NS). At the post‐trial evaluation of cytokine mucosal expression levels, IL‐10 significantly increased (P < 0.01) whereas IL‐1β, TNFα and IL‐8 significantly decreased (P < 0.01) only in the L. reuteri group. Conclusions In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease.     

髓过氧化物酶对炎症性肠病病情活动监测的临床价值

目的探讨髓过氧化物酶（MPO）作为炎症性肠病病情活动监测指标的临床价值。方法分别观察了15例IBD活动组患者[（其中活动期溃疡性结肠炎（UC）10例,活动期克罗恩病（CD）5例],15例IBD非活动组患者病人（其中缓解期UC10例．缓解期CD5例）,12例对照组患者结肠粘膜病理变化,按Oshitani评分标准和D＇haens评分标准进行UC和CD组织学评分．测定结肠黏膜MPO活性。结果IBD活动组、IBD非活动组病理组织评分均比对照组高,IBD活动组病理组织评分亦较IBD非活动组高．差异均有统计学意义（P〈0．01）。IBD活动组、IBD非活动组肠粘膜MPO活性均较对照组高,IBD活动组MPO活性较IBD非活动组高,差异均有统计学意义（P〈0．01）。结论MPO活性与IBD病情活动程度里正相关,可作为IBD病情活动的监测指标。     

Systematic review: steroid withdrawal in anti‐TNF‐treated patients with inflammatory bowel disease

Aliment Pharmacol Ther 2010; 32: 313–323

Summary

Background The increasing awareness of increased risk for opportunistic infections when combining several immunosuppressant drugs led to new treatment goals for inflammatory bowel disease including limited use of steroids. Aim To conduct a systematic review to establish figures for steroid withdrawal in anti‐TNF treated inflammatory bowel disease‐patients. Methods Medline was searched using the search‐terms Ulcerative Colitis (UC) [Mesh], Crohn Disease (CD) [Mesh], IBD [Mesh], crohn, colitis, IBD and steroid sparing, all combined with infliximab and adalimumab. We selected English‐language publications that addressed the effect of anti‐TNF on steroid withdrawal. Studies had to assess patients with luminal CD or UC. Numbers of patients who were able to withdraw steroids were calculated. Results Six studies could be included; five reporting on infliximab and one on adalimumab. Studies were heterogeneously designed. Overall, in the adult population, up to 38% of the patients were able to withdraw corticosteroids during infliximab therapy. In the paediatric population, up to 75% of the patients were able to withdraw corticosteroids during infliximab therapy. Conclusions Although a consensus on the definition of steroid‐sparing is lacking, approximately two‐thirds of the inflammatory bowel disease‐patients are unable to withdraw corticosteroid treatment during anti‐TNF therapy.     

Azathioprine or mercaptopurine‐induced acute pancreatitis is not a disease‐specific phenomenon

Aliment Pharmacol Ther 31 , 1322–1329

Summary

Background Several reports suggest an increased rate of adverse reactions to azathioprine in patients with Crohn’s disease. Aim To compare the incidence of thiopurine‐induced acute pancreatitis in patients with inflammatory bowel disease (IBD) with that in patients with vasculitis. Methods This retrospective analysis was performed using data collected in three databases by two university hospitals (241 patients with IBD and 108 patients with vasculitis) and one general district hospital (72 patients with IBD). Results The cumulative incidence of thiopurine‐induced acute pancreatitis in Crohn’s disease equalled that of ulcerative colitis (UC) (2.6% vs. 3.7%) and this did not differ from vasculitis patients (2.6% vs.1.9%). In addition, the cumulative incidence of thiopurine‐induced acute pancreatitis in UC patients was not different from that in vasculitis patients. In the IBD group, 100% of thiopurine‐induced acute pancreatitis patients were women, whereas in the vasculitis group the two observed thiopurine‐induced acute pancreatitis cases (n = 2 of 2) concerned were men (P = 0.012). Conclusions In this study, the alleged higher cumulative incidence of thiopurine‐induced acute pancreatitis in Crohn’s disease compared with vasculitis or UC patients was not confirmed. Female gender appears to be a risk factor for developing thiopurine‐induced acute pancreatitis in IBD patients.     

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

Aliment Pharmacol Ther 2011; 34: 188–195

Summary

Background Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods Among 910 eligible patients with more than a 7‐year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38‐43) between cohort enrolment and the end of follow‐up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results Only 54% (n = 312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P ≤ 0.0001). Surveillance rate was significantly lower in Crohn’s colitis than in ulcerative colitis (UC) (48% vs. 69%, P ≤ 0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high‐grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced‐stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis.     

Pre‐operative management is associated with low rate of post‐operative morbidity in penetrating Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Summary

Background Ileocaecal resection for penetrating Crohn’s disease is still challenging with a high rate of post‐operative morbidity and faecal diversion. Aim To report retrospectively the results of pre‐operative management for penetrating Crohn’s disease focusing on the rate of post‐operative major morbidities and need for faecal diversion. Methods Between 1997 and 2007, 78 patients with penetrating Crohn’s disease underwent a first ileocaecal resection after a pre‐operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate. Results Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre‐operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7–69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post‐operative death. Post‐operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post‐operative course was uneventful in 58 patients (74%). Conclusion Pre‐operative management for penetrating Crohn’s disease allowed ileocaecal resection with low rates of post‐operative morbidity and faecal diversion.     

C3435T polymorphism of the ABCB1/MDR1 gene encoding P-glycoprotein in patients with inflammatory bowel disease in a Polish population

BackgroundInflammatory bowel disease (IBD) belongs to the group of chronic diseases of the gastrointestinal tract, prevalence of which is increasing in the Polish population. The two main clinical types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). The expression level of the ABCB1/MDR1 gene which encodes P-glycoprotein seems to be of great prognostic relevance while evaluating patients’ susceptibility to UC or CD. One of the most significant ABCB1/MDR1 gene mutations is the C3435T polymorphism. A decreased expression of the ABCB1/MDR1 gene and lower P-glycoprotein activity has been associated with the 3435T variant. The aim of the study was to evaluate the C3435T polymorphism in the IBD patients and to investigate a possible correlation with disease susceptibility.MethodsThe study was performed on 108 patients with IBD and on 137 healthy individuals. All the participants were of Caucasian origin and came from central Poland. The C3435T polymorphism was analyzed by using the PCR-RFLP method.ResultsOur results showed that ORs for IBD development (including UC and CD) were elevated in individuals both with the 3435CC genotype and the 3435C allele. The differences in genotype and allele frequencies were not significant.ConclusionsThe C3435T polymorphism of the ABCB1/MDR1 gene is not a risk factor for IBD, including UC and CD, in the population coming from central Poland.     

Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis

BACKGROUND: Two variants in the organic cation transporter gene cluster have been recently reported to confer susceptibility to Crohn's disease (CD). AIM: To investigate these variants in CD and ulcerative colitis (UC), and their interaction with CARD15 gene and correlation to clinical subphenotypes. METHODS: Case-control association analysis was performed in 899 patients (444 CD and 455 UC) and 611 controls. The organic cation transporter gene cluster single nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length polymorphic analysis and multiplex pyrosequencing, respectively. RESULTS: The 1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P = 0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033), respectively. Compared with controls, the TC haplotype frequency was increased in both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15-negative CD, respectively. Similar results were found in UC. In CD a significant association of the TC haplotype was found with presence of perianal fistulae (P = 0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was more frequent in patients with more extensive disease (P = 0.015), and those on immunosuppressives (P = 0.004). CONCLUSIONS: Organic cation transporter gene cluster variants may confer susceptibility to both CD and UC, and the TC haplotype may influence some clinical features of IBD, but does not interact with CARD15 variants.     

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease

Aliment Pharmacol Ther 2011; 33: 946–953

Summary

Background Adalimumab is efficacious therapy for adults with Crohn’s disease (CD). Aim To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. Methods British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow‐up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn’s Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). Results Seventy‐two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric‐centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1–17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ²8.8, P = 0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). Conclusions Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.     

Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients

Background The long‐term efficiacy for thiopurinic drugs in Crohn’s disease (CD), and particularly in ulcerative colitis (UC), has been insufficiently studied. Aim To evaluate prospectively and compare the long‐term effectiveness of azathioprine (AZA) in CD and UC. Methods Three hundred and ninety‐four AZA treated patients were included consecutively included. Truelove‐modified index and CDAI were used to assess effectiveness. Hospitalizations and surgical procedures were recorded. Results Two hundred and thirty‐eight patients with CD and 156 with UC received AZA for a median of 38 months. Effectiveness: Partial response/remission was achieved in 34%/49% of CD patients and in 47%/42% of UC (nonstatistically significant differences). Steroid treatment: Prior to AZA, 49% of CD patients were receiving steroids, whereas only 8% needed steroids after therapy (P < 0.001). Corresponding figures in UC patients were 39% vs. 9% (P < 0.001). Hospitalizations: Prior to AZA, the rate of hospitalizations in CD was 0.190 per‐patient‐year, while after treatment, it decreased to 0.099 (P < 0.001). Corresponding hospitalization rates in UC were 0.108 vs. 0.038 (P < 0.001). Surgery: The rate of surgery in CD prior/after AZA was 0.038/0.011 per‐patient‐year (P < 0.001). The number of surgical interventions in UC prior/after AZA treatment was 26/0 (the rate per‐patient‐year was 0.018/0) (P < 0.001). Conclusions Our results confirm the effectiveness of AZA in inflammatory bowel disease, not only in the short term but also in the long term, resulting in a steroid sparing effect and in both a reduction in the number of hospitalizations and surgical procedures. AZA is similarly effective for both CD and UC patients.