Huorka M

Colorectal cancer screening in patients with ulcerative and Crohn's colitis with use of colonoscopy, chromoendoscopy and confocal endomicroscopy.

Background Patients with ulcerative colitis and Crohns colitis have increased risk of colorectal cancer. Current screening endoscopy protocols based on white light endoscopy (WLE) and random biopsies are laborious and of uncertain sensitivity. Novel endoscopic techniques include chromoendoscopy (CE) and confocal laser endomicroscopy (CLE). Aim The aim was to compare WLE and CE for the detection of intraepithelial neoplasia (IEN). Furthermore, we analysed the sensitivity and specificity of CE and CLE for the diagnosis of IEN. Methods The cohort consisted of 30 patients examined by WLE, CE with 0.4% indigocarmine, and by a CLE system Pentax EC-3870CIFK during one examination. Additional 15 patients were examined by conventional protocol only. Random biopsies and biopsies from all suspicious lesions were taken. We compared the number of IENs detected by WLE and CE and analysed the predictive values of CE and CLE for the histology diagnosis. Results There were 1584 random biopsies (35.2 per patient) taken. There were 78 targeted biopsies (1.7 per patient) taken in 24 of 45 patients examined by WLE and an additional 36 biopsies in 16 of 30 patients examined by CE (1.17 additional per patient). There were no IENs found on random biopsies versus six low-grade or high-grade IENs in four patients (two detected by WLE, four additional by CE) from targeted biopsies, P=0.02. A total of 100 suspicious lesions were detected and analysed by CE and histology. CLE could not examine 32 of 100 lesions (two of 30 flat vs. 30 of 70 pedunculated lesions, P=0.0002, odds ratio 10.5). The sensitivity of CE/CLE for low-grade or high-grade IEN was 100/100%, the specificity 96.8/98.4%, positive predictive value was 62.5/66.7% and negative predictive value was 100/100%. Conclusion Targeted biopsies are superior to random biopsies in the screening of IEN in patients with inflammatory bowel disease. CE increases the diagnostic yield of WLE. In our study CLE did not provide additional clinical benefits.

Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors

Abstract Cholelithiasis and nonalcoholic fatty liver disease (NAFLD) share the same risk factors. The aim of our study was to explore the relationship between these two conditions and to indentify independent predictors of both diseases in a cohort of patients with metabolic risk factors. Consecutive patients with metabolic risk factors referred to the outpatient clinic during a one-year period were included. Cholelithiasis was defined by the presence of gallstones on abdominal ultrasound examination at inclusion or previously performed cholecystectomy. NAFLD was defined by the presence of at least one surrogate marker such as elevated alanine aminotransferase and/or gamma-glutamyl transpeptidase and/or ultrasound signs of fatty liver. Other common liver diseases were thoroughly excluded. The prevalence of cholelithiasis among patients with and without NAFLD was determined and clinical and laboratory parameters were identified as predictors of NAFLD by multivariate logistic regression. In total, 482 consecutive patients were included: mean age 61 years; 61% were women; 52% of patients had more than 2 metabolic risk factors (obesity, type 2 diabetes, hypertension, hypertriglyceridemia, or low HDL cholesterol). NAFLD and cholelithiasis were present in 41% and 34% of all patients, respectively. Significantly higher prevalence of cholelithiasis was found among patients with NAFLD compared with patients without NAFLD (47% vs. 26%, respectively; p < 0.0001). In multivariate logistic regression model, type 2 diabetes (odds ratio (OR) = 1.99), BMI above 25 kg/m2 (OR = 1.78), and cholelithiasis (OR = 1.77) were identified as independent predictors of NAFLD. Fifty six percent of patients with cholelithiasis had NAFLD compared with 33% of patients without cholelithiasis (p < 0.0001). Multivariate logistic regression identified age above 50 years (OR = 3.46), NAFLD (OR = 1.92), triglycerides above 1.7 mmol/l (OR = 1.91), BMI above 25 kg/m2 (OR = 1.84), and total cholesterol concentration (OR = 0.711) as independent predictors of cholelithiasis. In conclusion, patients with metabolic risk factors and cholelithiasis suffer significantly more often from NAFLD compared with the reference group. Cholelithiasis represents an independent risk factor of NAFLD in addition to metabolic risk factors and could be regarded as an additional risk factor of liver damage in patients with NAFLD. Furthermore, NAFLD is an independent risk factor for cholelithiasis and might represent a pathogenetic link between the metabolic syndrome and cholelithiasis.

Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases.

AIM To investigate the effect of vitamin D (VD) concentrations and VD supplementation on health related quality of life in inflammatory bowel disease (IBD) patients. METHODS A cohort of 220 IBD patients including 141 Crohns disease (CD) and 79 ulcerative colitis (UC) patients was followed-up at a tertiary IBD center. A subgroup of the cohort (n = 26) took VD supplements for > 3 mo. Health related quality of life was assessed using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ score were assessed between August and October 2012 (summer/autumn period) and between February and April 2013 (winter/spring period). The mean VD serum concentration and its correlation with disease activity of CD were determined for each season separately. In a subgroup of patients, the effects of VD supplementation on winter VD serum concentration, change in VD serum concentration from summer to winter, and winter sIBDQ score were analyzed. RESULTS During the summer/autumn and the winter/spring period, 28% and 42% of IBD patients were VD-deficient (< 20 ng/mL), respectively. In the winter/spring period, there was a significant correlation between sIBDQ score and VD serum concentration in UC patients (r = 0.35, P = 0.02), with a trend towards significance in CD patients (r = 0.17, P = 0.06). In the winter/spring period, VD-insufficient patients (< 30 ng/mL) had a significantly lower mean sIBDQ score than VD-sufficient patients; this was true of both UC (48.3 ± 2.3 vs 56.7 ± 3.4, P = 0.04) and CD (55.7 ± 1.25 vs 60.8 ± 2.14, P = 0.04) patients. In all analyzed scenarios (UC/CD, the summer/autumn period and the winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 50-59 ng/mL. Supplementation with a median of 800 IU/d VD day did not influence VD serum concentration or the sIBDQ score. CONCLUSION VD serum concentration correlated with health related quality of life in UC and CD patients during the winter/spring period.

The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease.

AIM Osteoporosis is a known chronic complication of inflammatory bowel diseases (IBD). The aim of our study was to describe the prevalence of reduced bone mineral density (BMD) in IBD patients and to identify crucial risk factors for osteoporosis. METHODS The cohort consisted of 76 IBD patients, 40 with Crohns disease (CD) and 36 with ulcerative colitis (UC). Clinical characteristics of every patient were recorded, i.e. age, sex, duration of the disease, clinical behavior, location of disease according to Montreal classification, surgeries, steroid medication, sIBDQ, and smoking habits. We examined the serum 25-hydroxyl vitamin D3 (25-OHD3) in each patient. The BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck. RESULTS Osteoporosis was documented in 10 IBD patients (13.2 %), while osteopenia in 35 of them (46.1 %). Patients with CD have significantly lower femoral Z score than patients with UC. Femoral Z score was strongly associated with disease duration, and in CD patients suffering from stricturing form, with ileic or ileocolic location and history of proctocolectomy or total colectomy. Patients with osteoporosis had a significantly lower level of 25-OHD3 than patients with normal BMD. CONCLUSION Patients with long disease duration and those suffering from stricturing form of CD with ileic/ileocolic location and history of proctocolectomy/total colectomy are at higher risk of developing osteoporosis than other IBD patients. The high proportion of osteopenia/osteoporosis in our study underlines the importance of BMD measurement in all IBD patients as a base for initiating the appropriate treatment (Tab. 1, Fig. 3, Ref. 63).

Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients

OBJECTIVE There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it. DESIGN The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed. RESULTS The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL. CONCLUSIONS The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.

The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

BACKGROUND AND AIMS The thiopurine drugs, azathioprine (AZA) and 6-mercaptopurine, are established in the treatment of inflammatory bowel diseases (IBD). Polymorphisms in thiopurine S-methyltransferase (TPMT) gene have been associated with adverse drug reactions (ADRs) to AZA. METHODS The aim of this study was to evaluate TPMT polymorphisms and AZA-related toxicity in a Slovak cohort of 220 IBD patients treated with AZA. In every patient, the dose and duration of AZA therapy, concomitant 5-aminosalicylate (5-ASA) medication, frequency, type, time to onset, dose of ADR and concomitant 5-ASA at the onset of ADR were recorded. Each patient was also genotyped for the presence of variant TPMT alleles (*2,*3A,*3B,*3C). Frequency, type and circumstances of ADRs were compared according to TPMT status. RESULTS Of the 220 patients, 205 (93.2 %) were wild-type (TPMT*1/*1), one (0.5%) carried a TPMT*1/*3C allele, 13 (5.9 %) carried TPMT *1/*3A allele and one was homozygous for TMPT *3A allele. No TPMT *2 mutation was found. The incidence of adverse drug reactions was 62/205 (30.2 %) in the wild-type group as compared to 13/15 (86.7 %) in the TPMT mutation group, p=2.10-5. Leukopenia (WBC< 3.0*10^9/L) occurred in 21/205 (10.2 %) patients with wild type TPMT versus 11/15 (73.3 %) patients with TPMT mutations, p=0.000001. There was no significant difference between TMPT groups in gastrointestinal or other ADRs. No impact of 5-ASA on the incidence and severity of AZA adverse drug reactions was observed. CONCLUSION The incidence of leukopenia in TPMT mutant patients was significantly higher and more severe as compared to TPMT wild type patients. We observed no impact of concomitant 5-ASA therapy on AZA induced toxicity (Tab. 4, Fig. 2, Ref. 37).

Noninvasive scoring algorithm to identify significant liver fibrosis among treatment-naive chronic hepatitis C patients.

Aims Staging for liver fibrosis is recommended in the management of hepatitis C as an argument for treatment priority. Our aim was to construct a noninvasive algorithm to predict the significant liver fibrosis (SLF) using common biochemical markers and compare it with some existing models. Methods The study group included 104 consecutive cases; SLF was defined as Ishak fibrosis stage greater than 2. The patient population was assigned randomly to the training and the validation groups of 52 cases each. The training group was used to construct the algorithm from parameters with the best predictive value. Each parameter was assigned a score that was added to the noninvasive fibrosis score (NFS). The accuracy of NFS in predicting SLF was tested in the validation group and compared with APRI, FIB4, and Forns models. Results Our algorithm used age, alkaline phosphatase, ferritin, APRI, &agr;2 macroglobulin, and insulin and the NFS ranged from −4 to 5. The probability of SLF was 2.6 versus 77.1% in NFS<0 and NFS>0, leaving NFS=0 in a gray zone (29.8% of cases). The area under the receiver operating curve was 0.895 and 0.886, with a specificity, sensitivity, and diagnostic accuracy of 85.1, 92.3, and 87.5% versus 77.8, 100, and 87.9% for the training and the validation group. In comparison, the area under the receiver operating curve for APRI=0.810, FIB4=0.781, and Forns=0.703 with a diagnostic accuracy of 83.9, 72.3, and 62% and gray zone cases in 46.15, 37.5, and 44.2%. Conclusion We devised an algorithm to calculate the NFS to predict SLF with good accuracy, fewer cases in the gray zone, and a straightforward clinical interpretation. NFS could be used for the initial evaluation of the treatment priority.

Delayed hypersensitivity reaction after initial dose of infliximab: a case report.

We report here an unusual case of delayed hypersensitivity reaction in a young woman with ulcerative colitis after the first administration of infliximab (IFX). The patient developed severe serum-sickness-like reaction, and her anti-IFX antibody titer increased rapidly after a single infusion of IFX. The possible reason for the delayed hypersensitivity reaction to a single IFX exposure might be the presensitization of the patient by murine antigens as she had been keeping mice and hamsters as pets for several years.

Colorectal Cancer Screening in Patients With Ulcerative and Crohn's Colitis Using Chromoendoscopy and Confocal Endomicroscopy

in 20 consecutive patients ( M 9/20,45%; F 11/20, 55%; mean age 66.2+/7.6 SD). With portal hypertension diagnosed by clinical, ultra sonographic (US) and endoscopic criteria. The etiology of portal hypertension was hepatic cirrhosis in 15 patients (75%), portal cavernomatosi in 4 patients (20%) and portal vein thrombosis in 1 (5%). All patients underwent US and gastroscopy before performing CE examination. Results: Upper endoscopy showed F1 varices in 5 patients (25%), F2 varices in 7 patients (35%) and F3 varices in 6 patients (30%). Two patients (10%) did not present oesophageal varices. Ascites was present in 11/20 patients (55%). CE examination showed small bowel lesions due to portal hypertension in 16/20 patients (80%). Duodenal involvement occurred in 9 (40%) and jejunal lesions in 13 patients (65%) (<Lesions were found 7 times in proximal-, 9 times in mid, 8 times with distal jejunal involvement).Conclusion: Clinically relevant small bowel abnormalities are frequent in patients with portal hypertension, more so if oesophageal varices and/or ascites are present. Capsule endoscopy is an effective tool for their diagnosis Terminal ileum showed abnormal findings in 11 patients (55%). The entire jejunum was involved in 6 patients (30%). Lesions were classified as: bleeding or not-bleeding erosions and mucosal congestion with vascular ectasia. Most patients with positive CE had both erosions and mucosal congestion (12/16, 75%), 4 patients (25%) had erosions alone. All patients with positive CE had oesophageal varices. there was a significant association between abdominal ascites and CE findings (OR 1.7).

Sa1256 Combined Immunosuprpession, Corticoids and Menopause Have Significant Influcence on Bone Mineral Density in IBD Patients. A Prospective Study

a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG1-5 was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean MTXPGn concentration was observed between those with active disease and clinical remission. For each MTXPGn, a non-significant trend towards a higher measured concentration was observed in patients with active disease, (table 2). Conclusions: In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. References: [1]Dervieux T et al. Ann Rheum Dis,2005;64:1180-1185 [2]Stamp LK et al. Arth Rheum,2010;62:359-368 [3]Alenka JB et al,Ther Drug Mon,2007;29:619-625 Table 1. Patient Demographics