Bai-li Chen

Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies.

Background: Fecal calprotectin (FC) is a relatively new marker of intestinal inflammation. Recently, many studies have extended its role in predicting relapse of quiescent inflammatory bowel disease (IBD), but the reported results have been inconsistent. We aimed to perform a meta‐analysis of the predictive capacity of FC in IBD relapse. Methods: We systematically searched the Medline, Web of Science, Cochrane Library, and EMBASE databases for prospective studies that used FC concentrations at remission in predicting relapse of Crohns disease (CD) and ulcerative colitis (UC). Pooled sensitivity, specificity, and other diagnostic indices were evaluated. Results: A total of 672 IBD patients (318 UC and 354 CD) from six different studies were analyzed. The pooled sensitivity and specificity of FC to predict relapse of quiescent IBD was 78% (95% confidence interval [CI]: 72–83) and 73% (95% CI: 68–77), respectively. The area under the summary receiver‐operating characteristic (sROC) curve was 0.83 and the diagnostic odds ratio was 10.31 (95% CI: 5.05–21.06). The capacity of FC to predict relapse was comparable between UC and CD. In CD patients the predictive value of FC in isolated small bowel CD was not assessed due to insufficiency of available data. Compared with all enrolled CD patients, FC appeared to be more accurate in ileocolonic and colonic CD. Conclusions: As a simple and noninvasive marker, FC is useful to predict relapse in quiescent IBD patients. (Inflamm Bowel Dis 2012)

Systematic review with meta-analysis: magnetic resonance enterography vs. computed tomography enterography for evaluating disease activity in small bowel Crohn's disease.

Magnetic resonance enterography (MRE) has been proposed as a non‐ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohns disease (CD) with variable results.

Fecal calprotectin for evaluating postoperative recurrence of Crohn's disease: a meta-analysis of prospective studies.

Background:Fecal calprotectin (FC) levels have been extensively reported to correlate with clinical and endoscopic activities in Crohns disease (CD); however, the utility of FC levels in the postoperative setting remains to be determined. Using meta-analysis, we aimed to evaluate the utility of FC as a noninvasive marker of recurrence in patients with CD who had undergone previous surgical resection. Methods:An electronic search using keywords related to CD and FC was performed in multiple electronic resources from 1966 to March 2014. The extracted data were pooled using a hierarchical summary receiver operating curve model. Results:Ten articles met the inclusion criteria, and methodological quality was determined in detail for each study. The 10 studies presented FC levels in 613 postoperative CD patients. The pooled sensitivity and specificity values for assessing suspected endoscopic recurrence were 0.82 (95% confidence interval (CI), 0.73–0.89, 8 studies, n = 391) and 0.61 (95% CI, 0.51–0.71), respectively. The overall positive and negative likelihood ratios were 2.11 (95% CI, 1.68–2.66) and 0.29 (95% CI, 0.197–0.44), respectively. The pooled sensitivity and specificity values for evaluating clinical relapse were 0.59 (95% CI, 0.47–0.71; 3 studies, n = 183) and 0.88 (95% CI, 0.80–0.93), respectively. The overall positive and negative likelihood ratios were 5.10 and 0.47, respectively. Conclusions:As a simple and noninvasive marker, FC is useful in evaluating recurrence of postoperative patients with CD.

The potential influence of 5-aminosalicylic acid on the induction of myelotoxicity during thiopurine therapy in inflammatory bowel disease patients.

Objective To investigate the potential influence of 5-aminosalicylic acid (5-ASA) on the induction of myelotoxicity during thiopurine therapy in inflammatory bowel disease patients. Methods (a) The retrospective study included inflammatory bowel disease patients treated with azathioprine (AZA)/6-mercaptopurine (6-MP). Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) levels were detected at stable medication points. (b) The prospective study was performed in active disease patients: 4 weeks of AZA 50 mg/day followed by concomitant 5-ASA 3 g/day for another 4 weeks. 6-TGN was analyzed at weeks 4 and 8. Results (a) Of the 139 retrospective study patients, 45 were on AZA/6-MP+5-ASA and 94 on AZA/6-MP alone. The myelotoxicity rates were 47 and 16%, respectively. Multivariates regression analysis indicated that the administration of concomitant 5-ASA was the only risk factor associated with myelotoxicity (odds ratio=3.45, 95% confidence interval 1.31–9.04, P=0.01). (b) Thiopurine methyltransferase activity was not significantly different between patients on AZA/6-MP+5-ASA and patients on AZA/6-MP alone (P=0.78). (c) 6-TGN levels were significantly higher in samples on AZA/6-MP+5-ASA than those on AZA/6-MP (P=0.003) alone. (d) Sixteen patients completed the prospective study. After 4 weeks on AZA 50 mg/day, 6-TGN levels of 13 patients were less than 230 pmol/8×108 RBC. After another 4 weeks’ cotreatment with mesalazine 3 g/day, 12 patients had 6-TGN levels at least 230 pmol/8×108 RBC, five patients had 6-TGN levels at least 420 pmol/8×108 RBC, and two of these five patients developed myelotoxicity. Conclusion The risk of thiopurine-induced myelotoxicity markedly increases in patients treated with combined 5-ASA and 2 mg/kg/day AZA therapy, which may be correlated to the increase in 6-TGN. 50 mg daily AZA when concomitant 5-ASA might help maintain an effective 6-TGN level without increasing the risk of myelotoxicity.

Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease.

Background: Thiopurine drugs are widely used in the treatment of inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S‐methyltransferase (TPMT) is of importance for thiopurine metabolism and adverse events occurrence. The role of other thiopurine‐metabolizing enzymes is less well known. This study investigated the effects of TPMT and hypoxanthine guanine phosphoribosyltransferase (HPRT) activities on 6‐thioguanine nucleotides (6‐TGNs) concentrations and thiopurine‐induced leukopenia in patients with IBD. Methods: Clinical data and blood samples were collected from 120 IBD patients who were receiving azathioprine (AZA)/6‐mercaptopurine (6‐MP) therapy. Erythrocyte TPMT, HPRT activities and 6‐TGNs concentrations were determined. HPRT activity and its correlation with TPMT activity, 6‐TGNs level, and leukopenia were evaluated. Results: The HPRT activity of all patients ranged from 1.63–3.33 (2.31 ± 0.36) &mgr;mol/min per g Hb. HPRT activity was significantly higher in patients with leukopenia (27, 22.5%) than without (P < 0.001). A positive correlation between HPRT activity and 6‐TGNs concentration was found in patients with leukopenia (r = 0.526, P = 0.005). Patients with HPRT activity > 2.70 &mgr;mol/min per g Hb could have an increased risk of developing leukopenia (odds ratio = 7.47, P < 0.001). No correlation was observed between TPMT activity and HPRT activity, 6‐TGNs concentration, or leukopenia. Conclusions: High levels of HPRT activity could be a predictor of leukopenia and unsafe 6‐TGN concentrations in patients undergoing AZA/6‐MP therapy. This could partly explain the therapeutic response or toxicity that could not be adequately explained by the polymorphisms of TPMT. (Inflamm Bowel Dis 2011;)

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease.

Abstract Background and aims. To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohns disease (CD) patients. Methods. Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients – finished regular follow-up – were recruited for postoperative recurrence analysis. Results. One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291–3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064–7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060–7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218–0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59–19.766, p = 0.007). Conclusions. The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.

Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3

MicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo. Moreover, luciferase reporter assay, western blot analysis and microribonucleoprotein immunoprecipitation were performed to determine that miR-665 directly repressed XBP1 (X-box-binding protein-1) and ORMDL3 expression. Herein, our results revealed that miR-665 was markedly upregulated in active colitis. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-665 promoted apoptosis under different inflammatory stimuli. Importantly, delivery of miR-665 mimic promoted, while injection of antagomiR-665 markedly impaired DSS-induced colitis in vivo. Mechanistically, we demonstrated that miR-665 induced apoptosis by inhibiting XBP1 and ORMDL3. Taken together, our findings reveal a new regulatory mechanism for ER stress signaling and suggest that miR-665 might be a potential target in IBD therapy.

Imbalances of CD4+ T-cell subgroups in Crohn's disease and their relationship with disease activity and prognosis

The CD4+ T‐cell subgroups play central pathophysiological roles in Crohns disease (CD); however, their clinical relevance requires additional clarification and remains controversial. We investigated their balance in Chinese CD patients and explored their clinical significance.

Role of Helicobacter species in Chinese patients with inflammatory bowel disease.

ABSTRACT Based on 16S rRNA gene PCR, no significant difference was observed in rates of detection of Helicobacter species in intestinal biopsy specimens from 160 Chinese inflammatory bowel disease (IBD) patients (10%) and 80 controls (6.3%). By using a [13C]urea breath test, the H. pylori infection rate in 208 Chinese IBD patients (19.7%) was found to be significantly lower than that in 416 controls (48.8%).

Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease

BackgroundTo review the frequency with which anti-TNF-α loses its effect and dose “intensification” is required for Crohn’s disease (CD) treatment.MethodsElectronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.ResultsEighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29–38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22–39) for adalimumab, and 41% (95% CI 30–53) for certolizumabpegol. Overall, the mean percentage of patients’ LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28–41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28–50), 36% (95% CI 30–43) for adalimumab, and 2% (95% CI 2–3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001).ConclusionsOverall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders.