Fecal calprotectin is more accurate than fecal immunochemical test for predicting mucosal healing in quiescent ulcerative colitis: a prospective multicenter study

Abstract

Objective: Non-invasive stool tests, including the fecal immunochemical test (FIT) and fecal calprotectin (FC), are reliable biomarkers for mucosal healing (MH) in ulcerative colitis (UC). However, which fecal test is superior for predicting MH in inactive UC patients requires evaluation. We aimed to compare the accuracy of FIT and FC results for predicting MH in quiescent UC patients.

Methods: This prospective, multicenter study was conducted at three tertiary hospitals. UC patients in clinical remission for at least three?months underwent colonoscopy and MH was evaluated using the Mayo endoscopic sub-score (MES). The receiver operating characteristic (ROC) curve and cutoff value with the best accuracy for predicting MH were assessed.

Results: Among 127 patients, 65 (51.2%) showed MH (MES = 0). The area under the curve (AUC) for predicting MH (MES = 0) was significantly higher for FC than for FIT (AUC 0.858 (95% confidence interval (CI) 0.784–0.913) vs. 0.707 (95% CI 0.620–0.784), p?<?.001); there was no difference when MH included MES = 1 (MES ≤ 1) (AUC 0.820 (95% CI 0.742–0.883) vs. 0.813 (95% CI 0.734–0.877), p?=?.891). When the cutoff value was 70?μg/g for FC and 10?ng/mL for FIT, the sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3, respectively, for FC and 92.3, 50, 65.9, and 86.1, respectively, for FIT.

Conclusion: FC is more accurate than FIT for predicting MH in quiescent UC patients. The superiority of FC might be related to the distinctive performance of FC in differentiating inflammatory levels, particularly in low-grade mucosal activity.     

Assessment of disease activity by fecal immunochemical test in ulcerative colitis

AIM To evaluate the efficacy of quantitative fecal immunochemical test(FIT) as biomarker of disease activity in ulcerative colitis(UC).METHODS Between February 2013 and November 2014, a total of 82 FIT results, obtained in conjunction with colonoscopies, were retrospectivelyevaluated for 63 patients with UC. The efficacy of FIT for evaluation of disease activity was compared to colonoscopic findings. Quantitative fecal blood with automated equipment examined from collected feces. Endoscopic disease severity were assessed using the Mayo endoscopic subscore(MES) classification. The extent of disease were classified by proctitis(E1), left sided colitis(E2), and extensive colitis(E3). Clinical activity were subgrouped by remission or active.RESULTS All of 21 patients with MES 0 had negative FIT( 7 ng/mL), but 22 patients with MES 2 or 3 had a mean FIT of 134.89 ng/m L. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and accuracy of negative FIT about mucosal healing were 73.33%, 81.82%, 91.49%, 51.43% and 73.17%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of predictive value of positive FIT(cutoff value 100 ng/mL) about active disease status were 45.45%, 93.33%, 71.43%, 82.35%and 26.83%, respectively. Among patients with clinical remission, FIT was negative in 31(81.6%) of 38 cases, with a mean fecal hemoglobin concentration of 6.12 ng/mL(range, negative to 80.9 ng/mL) for this group of patients. Among patients with clinical active disease, FIT was negative in 16(36.4%) out of 44 cases, with a mean fecal hemoglobin concentration 167.4 ng/mL for this group of patients. FIT was positively correlated with endoscopic activity(r = 0.626, P 0.01) and clinical activity(r = 0.496, P 0.01). But, FIT did not correlate with the extent of disease(r =-0.047, P = 0.676)CONCLUSION Quantitative FIT can be a non-invasive and effective biomarker for evaluation of clinical and endoscopic activity in UC, but not predict the extent of disease.     

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing,which can be predicted from the platelet count

AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.METHODS: UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05.RESULTS: A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 × 10⁴/μL was an independent predictive factor for complete mucosal healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 × 10⁴/μL vs -0.6 × 10⁴/μL, P < 0.0001).CONCLUSION: The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT.     

Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: A meta-analysis

AIM:To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease(IBD)by conducting a meta-analysis.METHODS:Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD.The search terms were:"herb"or"plant"or"herbal"and"inflammatory bowel disease".Data were collected from 1966 to 2013(up to Feb).The"clinical response","clinical remission","endoscopic response","endoscopic remission","histological response","histological remission","relapse","any adverse events",and"seriousadverse events"were the key outcomes of interest.We used the Mantel-Haenszel,Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects.For subgroup analyses,we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.RESULTS:Seven placebo controlled clinical trials met our criteria and were included(474 patients).Comparison of herbal medicine with placebo yielded a significant RR of 2.07(95%CI:1.41-3.03,P=0.0002)for clinical remission;a significant RR of 2.59(95%CI:1.24-5.42,P=0.01)for clinical response;a non-significant RR of 1.33(95%CI:0.93-1.9,P=0.12)for endoscopic remission;a non-significant RR of 1.69(95%CI:0.69-5.04)for endoscopic response;a non-significant RR of 0.64(95%CI:0.25-1.81)for histological remission;a non-significant RR of 0.86(95%CI:0.55-1.55)for histological response;a non-significant RR of 0.95(95%CI:0.52-1.73)for relapse;a non-significant RR of 0.89(95%CI:0.75-1.06,P=0.2)for any adverse events;and a non-significant RR of 0.97(95%CI:0.37-2.56,P=0.96)for serious adverse events.CONCLUSION:The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes,but the number of studies is limited to make a strong conclusion.     

应用米兰标准微波消融治疗肝细胞癌患者预后及其影响因素分析*

目的 探讨应用米兰标准施行微波消融术(MWA)治疗肝细胞癌(HCC)患者影响生存的因素。方法 2013年1月～2016年12月我院消化内科住院的94例直径≤5 cm的HCC患者接受超声引导下MWA治疗,随访5年。分析不同HCC结节个数和不同肿瘤直径对总生存率(OS)和无进展生存率(PFS)的影响。结果 随访5年,本组HCC患者OS为64.9%,1 a和2 a 肿瘤复发率分别为12.8%和53.2%;HCC直径> 3 cm患者的PFS显著短于直径≤3 cm的患者(P=0.005),PFS≤2年的HCC患者OS显著低于PFS> 2年的患者(48.0%对 84.1%,P<0.001);多因素回归分析显示HCC直径> 3 cm (HR=0.42,95%CI:0.21～0.83,P=0.01)是MWA术后肿瘤复发的独立危险因素,而白细胞计数< 4.0×10⁹ /L (HR=0.38, 95%CI:0.18～0.84,P=0.017)和PFS≤2 年(HR=0.24, 95%CI:0.10～0.56,P=0.001)是影响HCC患者OS的独立危险因素。结论 直径> 3 cm的HCC患者PFS较短,但似乎不影响OS,因为大多数肝内复发的HCC患者仍然可进行重复MWA治疗。     

Long-term Outcomes after the Discontinuation of Anti-Tumor Necrosis Factor-α Therapy in Patients with Inflammatory Bowel Disease under Clinical Remission: A Korean Association for the Study of Intestinal Disease Multicenter Study

Background/AimsOur study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established.MethodsA retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued first-line anti-TNF therapy after achieving clinical remission.ResultsA total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4).ConclusionsMore than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response. (Gut Liver 2021;15-762)     

Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission

Objective: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0.

Methods: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a ‘0 point’ of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed.

Results: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12–118) months. Factors predictive of longer clinical remission duration were age ≥30 years at diagnosis (≥30 years vs. <30 years; hazard ratio [HR] 3.16, 95% CI 1.88–5.30, p?p?=?0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15–3.32, p?=?0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH.

Conclusion: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis.     

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease – a systematic review with meta-analysis

BackgroundThe efficacy and safety of vedolizumab in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) remain unknown.AimsTo perform a meta-analysis regarding vedolizumab as first line of biological therapy for UC or CD.MethodsA systematic review of Medline, EMBASE, and Cochrane databases per December 2020 was undertaken. Meta-analysis was conducted using random-effects models.ResultsThis systematic review identified 79 eligible studies with 4,520 and 3,494 bio-naïve patients with UC and CD, respectively, and 8,105 and 11,140 bio-exposed patients. Among bio-naïve patients with UC, a total of 40.0% (95%CI 27.0–54.0, I²=86%) and 63.9% (95%CI 47.0–79.2, I²=36%) achieved clinical remission at weeks 14 and 52, respectively. The corresponding rates in CD were 54.0% (95%CI 42.0–66.0, I²=23%), and 61.7% (95%CI 55.2–68.1, I²=0%). Bio-naïvety was associated with a higher probability of clinical remission at week 52 in UC (relative risk (RR)=1.32 (95%CI 1.14–1.53)), while this was only apparent until week 26 in CD (RR=1.60 (95%CI 1.30–1.95)). Finally, bio-naïve UC patients had a lower risk of serious adverse events (RR=0.29 (95%CI 0.09–0.95)).ConclusionVedolizumab was found to have a favorable efficacy and safety profile in bio-naïve patients with UC and CD. The findings have implications in the management of IBD.     

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn&rsquo;s disease

AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn’s disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006). CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.     

Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.     

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.     

Twist2 is a valuable prognostic biomarker for colorectal cancer

AIM: To investigate the significance of Twist2 for colorectal cancer (CRC). METHODS: In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients’ clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox’s proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. RESULTS: Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P=0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR)=7.694, 95%CI: 2.927-20.224,P < 0.001] and Twist2-positive (HR=5.744, 95%CI: 1.347-24.298,P=0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR=3.264, 95%CI: 1.455-7.375, P=0.004), bad N-stage (HR=2.149, 95%CI: 1.226-3.767, P=0.008) and bad M-stage (HR=10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS     

Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease

BACKGROUND AND AIMS: The clinical course of inflammatory bowel disease is characterised by a succession of relapses and remissions. The aim of our study was to assess whether the predictive value of faecal calprotectin-a non-invasive marker of intestinal inflammation-for clinical relapse is different in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Seventy nine consecutive patients with a diagnosis of clinically quiescent inflammatory bowel disease (38 CD and 41 UC) were followed for 12 months, undergoing regular clinical evaluations and blood tests. A single stool sample was collected at the beginning of the study from each patient and the calprotectin concentration was assessed by a commercially available enzyme linked immunoassay. RESULTS: In CD, median calprotectin values were 220.1 mug/g (95% confidence interval (CI) 21.7-418.5) in those patients who relapsed during follow up, and 220.5 mug/g (95% CI 53-388) in non-relapsing patients (p=0.395). In UC, median calprotectin values were 220.6 mug/g (95% CI 86-355.2) and 67 microg/g (95% CI 15-119) in relapsing and non-relapsing patients, respectively (p<0.0001). The multivariate Cox (proportional hazard) regression model, after adjustment for possible confounding variables, showed a twofold and 14-fold increase in the relapse risk, respectively, in those patients with CD and UC in clinical remission who had a faecal calprotectin concentration higher than 150 microg/g. CONCLUSIONS: Faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy.     

Infliximab is superior to other biological agents for treatment of active ulcerative colitis:A meta-analysis

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis(UC).METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixedtreatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software.The proportions of patients reaching clinical response,clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators.RESULTS: The meta-analysis results showed that biological agents achieved better clinical response,clinical remission and mucosal healing than placebo.Indirect comparison indicated that in induction phase,infliximab was more effective than adalimumab in inducing clinical response(OR = 0.41, 95%CI:0.29-0.57), clinical remission(OR = 0.33, 95%CI:0.19-0.56) and mucosal healing(OR = 0.33, 95%CI:0.19-0.56), and golimumab in inducing clinical response(OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing(OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety.CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.     

-449 C>G polymorphism of NFKB1 gene,coding nuclear factor-kappa-B,is associated with the susceptibility to ulcerative colitis

AIM: To clarify the association between a polymorphism -449 C>G (rs72696119) in 5’-UTR of NFKB1 with ulcerative colitis (UC).METHODS: The studied population comprised 639 subjects, including patients with UC (UC cases, n = 174) and subjects without UC (controls, n = 465). We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS: The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%, respectively (P = 0.10). Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls (P = 0.017), and the GG homozygote was significantly associated with susceptibility to UC [odds ratio (OR), 1.88; 95%CI, 1.13-3.14]. In male subjects, the GG homozygote was associated with an increased risk for UC (OR, 3.10; 95%CI, 1.47-6.54; P = 0.0053), whereas this association was not found in female subjects. In addition, the GG homozygote was significantly associated with the risk of non-continuous disease (OR, 2.06; 95%CI, 1.12-3.79; P = 0.029), not having total colitis (OR, 2.40; 95%CI, 1.09-3.80, P = 0.040), disease which developed before 20 years of age (OR, 2.80; 95%CI, 1.07-7.32, P = 0.041), no hospitalization (OR, 2.28; 95%CI, 1.29-4.05; P = 0.0090) and with a maximum of 8 or less on the UCDAI score (OR, 2.45; 95%CI, 1.23-4.93; P = 0.022).CONCLUSION: Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC. This polymorphism influences the susceptibility to and pathophysiological features of UC.     

Histopathology of type C liver disease for determining hepatocellular carcinoma risk factors

AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon therapy.The patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 groups.Then,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing HCC.RESULTS:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 group.The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.     

Can calprotectin predict relapse risk in inflammatory bowel disease?

OBJECTIVE:  Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in predicting clinical relapse in IBD patients.
METHODS:  Ninety-seven patients with ulcerative colitis (UC) and 65 with Crohn's disease (CD) in clinical remission were prospectively included in the study. A 10-g stool sample was collected for calprotectin assay. The cutoff level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the test or until relapse. The cumulative proportion of relapses was estimated by the Kaplan-Meier analysis. Statistics for equality of survival distribution were tested using the log-rank test.
RESULTS:  The calprotectin test was positive in 44 UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients with a negative calprotectin test relapsed within the same time frame. Thirty CD patients had a positive calprotectin test and 13 of them relapsed within a year, as did 7 of the 35 with a negative test result. A significant correlation emerged between a positive calprotectin test and the probability of relapse in UC patients ( P = 0.000). In CD patients, only cases of colonic CD showed a significant correlation between a positive calprotectin test and the probability of relapse, i.e ., 6 colonic CD patients were positive for the calprotectin test and 4 relapsed ( P = 0.02).
CONCLUSIONS:  Measuring calprotectin may help to identify UC and colonic CD patients at higher risk of clinical relapse.     

Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy

Objective: We investigated relapse rates after anti-tumor necrosis factor (anti-TNF) withdrawal in inflammatory bowel disease (IBD) patients, response to restart of anti-TNF treatment and predictors for relapse.

Methods: IBD patients in remission receiving infliximab or adalimumab treatment for ≥1 year who discontinued treatment were included. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results: In total, 101 patients were included (77?CD, 24 UC). A total of 56 patients (55%) experienced a relapse (CD 38, UC 18) with a median time to relapse of 32 and 18 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agent, 84% responded. A trough serum concentration ≥2 µg/ml within 1 year prior to anti-TNF discontinuation was associated with a higher relapse rate in CD patients (HR 2.89; p?=?.018), which was more evident in patients requiring retreatment with biologicals, bowel-related surgery or experimental medication (HR: 4.18; p?=?.009). A young age (<17 years) at diagnosis was associated with a higher relapse rate (HR: 2.29; p?=?.040) and fecal calprotectin levels <25?µg/g with a lower relapse rate in CD patients (HR: 0.34; p?=?.041). Relapse rates, requiring treatment with biologicals or experimental medication, was lower in UC patients who continued immunosuppressive treatment (HR: 0.26; p?=?.042).

Conclusions: Approximately 55% of patients relapsed after anti-TNF withdrawal with a median time to relapse of 32 and 18 months in CD and UC, respectively. Retreatment with the same anti-TNF was successful in 84% of patients.     

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.     

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study

Background & AimsThe combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use.MethodsIn a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥ 1 year and ≥ 2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments.ResultsIBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p = n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL,1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08–1.45; UC:HR 1.33;95%CI 1.15–1.55 for an increase by 5 years; p = 0.0023; p = 0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11–5.86,p = 0.0275), pancolitis in UC (HR 2.79;95%CI 1.05–7.40 p = 0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed).ConclusionsFistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.