Effects of anti–TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease

BackgroundTumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti–TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown.MethodsAnalytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy.Results29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ± SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98–8.45) and elevated CRP (OR 3.45; 95CI 1.29–9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07–9.16).ConclusionsControlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

炎症性肠病相关性肝病的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种累及回肠、结肠、直肠的特发性炎症性疾病,本病主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。除常见的消化道症状外,研究发现IBD合并肝脏疾病较为常见,是IBD常见的肠外表现之一,其严重影响IBD的预后与转归。本文就IBD相关性肝病的分类和总结作一概述,以期为IBD及其肝脏病变的临床诊疗提供参考。     

Idiopathic acute pancreatitis in patients with inflammatory bowel disease: A multicenter cohort study

BackgroundIdiopathic acute pancreatitis (IAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history.MethodsRetrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. IAP and non-IAP were compared by multivariate logistic regression and survival analysis.ResultsWe identified 185 patients with IBD (68.7% Crohn’s disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for IAP. There were no severe cases of IAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in IAP. Further work-up was performed in 16/38 (42%) IAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1–10). Five-year risk of AP recurrence was significantly higher in IAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9–12.2).ConclusionsIAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of IAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Anti-pancreatic antibody in Turkish patients with inflammatory bowel disease and first-degree relatives

AIM: To identify the role of anti-pancreatic antibody (PAB) in the diagnosis of inflammatory bowel diseases (IBD) among Turkish patients, and its frequency in firstdegree relatives.METHODS: PAB and anti-Saccharomyces cerevisiae (ASCA) were examined in serum samples of 214 subjects including patients with Crohn’s disease (CD, n = 64), ulcerative colitis (UC, n = 63), first-degree relatives of patients with CD (n = 25), first-degree relatives of patients with UC (n = 28),and a control group with gastrointestinal symptoms other than (IBD) (n = 34) by indirect immunofluorescence Positivity of PAB and ASCA was compared in terms of Vienna classification, disease activity and medications used.RESULTS: In terms of PAB positivity, no difference was found between patients with CD (14.1%) and UC (7.9%) however, significant difference was observed between patients with CD and subjects in the control group (P < 0.05). No difference was found between patients with CD and their relatives in terms of ASCA positivity, whereas a significant difference was found between other groups (P < 0.001). Compared to ASCA, the sensitivity of the PAB was 19% (7/37), its specificity was 93% (25/27), positive predictive value was 77% (7/9) and negative predictive value was 45% (25/55). ASCA was found with significantly higher prevalence in patients with CD activity index > 150 (P < 0.05).CONCLUSION: PAB is valuable in the diagnosis of IBD rather than CD, but cannot be used alone for diagnostic purposes. PAB is not superior to ASCA in CD diagnosis and in detecting CD among relatives of patients with CD.     

Updates in therapeutic drug monitoring in inflammatory bowel disease

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn’s disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

Urotensin II levels in patients with inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIMTo determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters.METHODSThis cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn’s disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer’s instructions.RESULTSIBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn’s disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn’s Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030).CONCLUSIONIt is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.     

Hospitalizations and in-hospital mortality for inflammatory bowel disease in Brazil

BACKGROUND Inflammatory bowel disease(IBD)is associated with complications,frequent hospitalizations,surgery and death.The introduction of biologic drugs into the therapeutic arsenal in the last two decades,combined with an expansion of immunosuppressant therapy,has changed IBD management and may have altered the profile of hospitalizations and in-hospital mortality(IHM)due to IBD.AIM To describe hospitalizations from 2008 to 2018 and to analyze IHM from 1998 to 2017 for IBD in Brazil.METHODS This observational,retrospective,ecological study used secondary data on hospitalizations for IBD in Brazil for 2008-2018 to describe hospitalizations and for 1998-2017 to analyze IHM.Hospitalization data were obtained from the Hospital Information System of the Brazilian Unified Health System and population data from demographic censuses.The following variables were analyzed:Number of deaths and hospitalizations,length of hospital stay,financial costs of hospitalization,sex,age,ethnicity and type of hospital admission.RESULTS There was a reduction in the number of IBD hospitalizations,from 6975 admissions in 1998 to 4113 in 2017(trend:y=-0.1682x+342.8;R²=0.8197;P<0.0001).The hospitalization rate also decreased,from 3.60/100000 in 2000 to 2.17 in 2010.IHM rates varied during the 20-year period,between 2.06 in 2017 and 3.64 in 2007,and did not follow a linear trend(y=-0.0005049x+2.617;R²=0,00006;P=0.9741).IHM rates also varied between regions,increasing in all but the southeast,which showed a decreasing trend(y=-0.1122x+4.427;R²=0,728;P<0.0001).The Southeast region accounted for 44.29%of all hospitalizations.The Northeast region had the highest IHM rate(2.86 deaths/100 admissions),with an increasing trend(y=0.1105x+1.110;R²=0.6265;P<0.0001),but the lowest hospitalization rate(1.15).The Midwest and South regions had the highest hospitalization rates(3.27 and 3.17,respectively).A higher IHM rate was observed for nonelective admissions(2.88),which accounted for 81%of IBD hospitalizations.The total cost of IBD hospitalizations in 2017 exhibited an increase of 37.5%compared to 2008.CONCLUSION There has been a notable reduction in the number of hospitalizations for IBD in Brazil over 20 years.IHM rates varied and did not follow a linear trend.     

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.     

Comorbidity in inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) can be affected by other unrelated diseases. These are called comorbid conditions, and can include any secondary health problem that affects a person suffering from a primary or main disease, and which is neither linked physiopathologically to the primary condition, nor is it due to the treatments used for the primary condition or to its long-term anatomical or physiological consequences. Different comorbid conditions, as well as their influence on IBD, are dis...     

Sexual health and fertility for individuals with inflammatory bowel disease

The impact of a chronic disease such as inflammatory bowel disease(IBD) on sexual functioning and body image can significantly impair the quality of life of patients. This review considers the sexual and fertility aspects of IBD patients and their daily management. Modern IBD healthcare management should include appropriate communication on sexuality and consider psychological,physiological, and biological issues. Patients with IBD have less children than the general population, and voluntary childlessness is frequent. The most influential factors reported by IBD patients who experience fertility alteration are psychological and surgery-related problems. Pregnancy is a major concern for patients, and any pregnancy for IBD patients should be closely followed-up to keep the chronic disease in a quiescent state. Preconceptional consultation is of great help.     

肠易激综合征与炎症性肠病

近年发现,炎症性肠病(IBD)患者发病早期或缓解期时常表现为肠易激综合征(IBs)症状,且IBD与IBS的临床表现具有一定的相似性。因而IBS与IBD的相关性受到广泛的重视。此文就IBS与IBD的发病机制及临床相关性予以阐述,以期为临床个体化治疗提供借鉴。     

Predicting(side) effects for patients with inflammatory bowel disease: The promise of pharmacogenetics

Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.     

Pulmonary involvement in inflammatory bowel disease

AIM:To determine the relationship of pulmonary abnormalities and bowel disease activity in inflammatory bowel disease(IBD).METHODS:Thirty ulcerative colitis(UC)and nine Crohn’s disease patients,and 20 control subjects were enrolled in this prospective study.Detailed clinical information was obtained.Extent and activity of the bowel disease were established endoscopically.Each patient underwent pulmonary function tests and high-resolution computed tomography(HRCT).Blood samples for measurement of C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),angiotensin converting enzyme and total IgE were delivered by the patients.RESULTS:Ten(25.6%)patients had respiratory symptoms.A pulmonary function abnormality was present in 22 of 39 patients.Among all patients,the most prevalent abnormalities in lung functions were a decrease in forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),forced expiratory flow(FEF)25%-75%,transfer coefficient for carbon monoxide(DLCO),DLCO/alveolar volume.Increased respiratory symptoms score was associated with high endoscopic activity index in UC patients.Endoscopic and clinical activities in UC patients were correlated with FEV1,FEV1/FVC,and FEF 25%-75%.Smoking status,duration of disease and medication were not correlated with pulmonary physiological test results,HRCT abnormalities,clinical/endoscopic disease activity,CRP,ESR or total IgE level or body mass index.CONCLUSION:It is important that respiratory manifestations are recognized and treated early in IBD.Otherwise,they can lead to destructive and irreversible changes in the airway wall.     

Accuracy of fecal calprotectin for the prediction of endoscopic activity in patients with inflammatory bowel disease

BackgroundFecal calprotectin is a noninvasive marker of inflammatory bowel disease.AimTo evaluate the accuracy of calprotectin for prediction of endoscopic activity in inflammatory bowel disease.MethodsOne-hundred patients were prospectively included. Quantum Blue^® (Bühlmann) kits were used to determine calprotectin. Endoscopic activity was calculated. Various serum markers (platelets, leukocytes, C-reactive protein, and albumin) were recorded.ResultsCalprotectin was higher in patients with endoscopic activity than in those without activity: in ulcerative colitis, with the low- (29 ± 14 vs. 301 ± 174, p < 0.001) and high- (99 ± 727 vs. 617 ± 801, p < 0.001); and in Crohn’s disease, with the low- (29 ± 59 vs. 124 ± 268, p < 0.01) and high-range kit (99 ± 37 vs. 287 ± 607, p < 0.01). Serological marker concentrations did not vary with endoscopic activity. The area under the ROC curve of calprotectin for the prediction of endoscopic activity was 0.9 in ulcerative colitis and 0.8 in Crohn’s disease. The best cut-off points for the detection of activity in ulcerative colitis were 50 for the low- (sensitivity 85%, specificity 79%) and 102 for the high- (sensitivity 85%, specificity 79%); in Crohn’s disease, 54 for the low- (sensitivity 71%, specificity 75%) and 122 for the high-range kit (sensitivity 71%, specificity 75%).ConclusionsFecal calprotectin concentration has good diagnostic accuracy for the detection of endoscopic activity in inflammatory bowel disease and performs better in ulcerative colitis than in Crohn’s disease.     

当前炎症性肠病诊治中需注意的若干问题

我国炎症性肠病患者逐年增多，但目前临床对其认识或重视仍显不足，亟待规范化地开展诊疗。根据同济大学附属同济医院消化科临床实践体会和文献报道，对当前炎症性肠病诊治中需注意的诊断、鉴别诊断、规范化个体化治疗的若干问题进行了分析，以期引起消化专科医师的重视。