BackgroundChronic hepatitis C (CHC) is a global health challenge. New therapeutic agents with excellent sustained virological response (SVR) rates are available mainly in developed countries, while the majority of CHC patients live in countries with low health budget. Predictors of therapeutic response are therefore necessary. Vitamin B12 appears to be involved in hepatitis C virus replication.MethodsWe therefore studied retrospectively the relationship between baseline serum vitamin B12 levels and clinical features in 116 CHC genotype 1 infected patients. Logistic regression models with univariate and multivariate analysis were used in the statistical analysis.ResultsBaseline serum vitamin B12 levels were found to be positively associated with serum transaminase activities (AST, p = 0.002, ALT, p = 0.04), baseline viral load (p < 0.0001), stage of fibrosis (p = 0.0001) and favorable interferon-λ3/4 (IFNL3/IFNL4) rs12979860 genotypes (p = 0.04), and inversely with SVR (p < 0.001) as well as with rapid virological response (p = 0.001). Patients with baseline serum vitamin B12 levels below a cut-off value of 570 ng/L achieved a SVR rate of 59% with an odds ratio (OR) of 13.4 [confidence interval (CI) 4.3–41.9, p < 0.0001] compared to patients above the cut-off value. By combining serum vitamin B12 levels and IFNL3/IFNL4 rs12979860 genotypes, patients with baseline serum vitamin B12 levels below the cut-off value of 570 ng/L and IFNL3/IFNL4 rs12979860 CC genotype achieved a SVR rate of even 80% with an OR of 54 (CI 9.9–293, p < 0.0001) compared to patients above the cut-off value and non-CC-genotypes.ConclusionOur data suggest baseline serum vitamin B12 levels as useful noninvasive marker for characterizing CHC patients. They might further help to identify responders to a standard treatment.

Background: Colorectal cancer (CRC) is the leading gastrointestinal malignancy. The development from premalignant intraepithelial lesions leading to invasive cancer is paradigmatic for the stepwise carcinogenesis of epithelial cancers, but the knowledge of the underlying mechanism of carcinogenesis and progression of CRC is still incomplete. The understanding of epigenetic mechanisms of carcinogenesis has led to new therapeutic approaches during the last years. Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities. Patients and Methods: The protein expression of EZH2 and other members of the PRC2 as well as resulting posttranslational modifications were investigated by immunohistochemistry in 187 patients with CRC and in 94 patients with premalignant colorectal lesions and correlated with their clinical outcome. Furthermore, the corresponding mRNA expression levels were analyzed in 217 patients with rectal cancer that were enrolled in a prospective clinical trial. Results: We found a weak expression of EZH2 in normal colon mucosa that increased in low grade, peaked in high grade intraepithelial neoplasia, and decreased again in invasive CRC. The posttranslational modification caused by EZH2 as a measure of EZH2 activity showed the same behavior. Strong protein and mRNA expression of EZH2 were significantly correlated with favorable prognosis in both investigated cohorts. Conclusion: The expression and activity of EZH2 are associated with colorectal carcinogenesis and most expressed in intraepithelial high-grade lesions. Strong expression of EZH2 is associated with a significantly favorable prognosis in patients suffering from CRC.

Crohn's disease (CD) and ulcerative colitis (UC) are characterized by overexpression of proinflammatory cytokines. We determined the association of serum levels of interleukin (IL)-6, soluble-IL-2-receptor (sIL-2R) and CRP as well as of faecal calprotectin (FC) values with disease activity in CD and UC patients. This prospective study included 145 CD and 84 UC patients. Serum proinflammatory biomarkers and FC levels were measured and demographic, clinical and endoscopic characteristics were collected. Uni-and multivariate statistical analyses were performed. Serum IL-6 and CRP levels as well as FC values of CD patients were associated with clinical and endoscopic remission. In multivariate analysis serum IL-6 levels remained significantly associated with clinical and endoscopic remission. FC levels were also associated with endoscopic remission in CD patients. CD patients under the threshold levels of 8.5 pg/mL and 5.5 pg/mL for serum IL-6 were in 70% and 66% in clinical and endoscopic remission, respectively. Serum sIL-2R, CRP levels and FC values of UC patients were associated in univariate analysis with clinical and endoscopic remission. In multivariate analysis CRP and FC values were associated with clinical remission and serum sIL-2R as well as FC levels with endoscopic remission. UC patients under the threshold levels of 759 IU/mL and 646 IU/mL for serum sIL-2R were in 76% and 76% in clinical and endoscopic remission, respectively. Beside CRP and FC, serum IL-6 levels in CD patients and sIL-2R levels in UC patients can be a further useful non-invasive biomarker to identify the disease activity status.

The incidence of inflammatory bowel disease (IBD) is increasing and the pathogenesis is still not completely understood. Micronutrients like vitamin D [25 (OH)D] and zinc play an important role in enzyme activities and the immune system. As the 25 (OH)D-receptor has been shown to be downregulated in patients with IBD, 25 (OH)D may emerge as a predictive marker for disease improvement. Studies on relationship of both micronutrients in IBD patients are lacking. We retrospectively evaluated serum levels of 25(OH)D and zinc together with baseline characteristics of 232 IBD patients. Uni- and multivariate analyses were performed for association between serum levels of 25(OH)D and zinc with clinical and deep remission (CR and DR). 155 Crohn's disease (CD) and 77 ulcerative colitis (UC) patients were included. 54% (n = 125) and 6% (n = 14) of IBD patients showed deficient serum 25(OH)D levels below 20 ng/mL and zinc levels below 7 μmol/L. Serum 25(OH)D levels were significantly higher in IBD patients with CR ( P = .02) and DR ( P < .001) but not serum zinc levels, respectively. Serum 25(OH)D levels ( P = .008), anti-tumor-necrosis-factor-α-trough-concentration (anti-TNF-α-TC) ( P = .02) and CRP level ( P = .02) were independently associated with CR in CD patients. Serum 25(OH)D threshold of 19 ng/mL discriminated CD patients with or without CR, having an area under the receiver operating curve analysis (AUROC) of 0.77 [95%-confidence interval (CI): 0.68–0.85]. In multivariate analysis serum 25(OH)D levels ( P = .04) and anti-TNF-α-TC ( P = .04) were associated with DR in CD patients. Serum 25(OH)D threshold of 26 ng/mL discriminated CD patients with or without DR, having an AUROC of 0.75 (95%-CI: 0.68–0.83). Serum 25(OH)D ( P = .04) and fecal calprotectin levels ( P = .04) were independently correlated with CR in UC patients. Serum 25(OH)D threshold of 32 ng/mL discriminated UC patients in CR with an AUROC of 0.83 (95%-CI: 0.71–0.95). Zinc levels did not correlate with disease activity status in CD or UC patients either. In conclusion, beside CRP and fecal calprotectin, serum 25(OH)D levels, but not serum zinc levels, may be an additional useful and noninvasive marker for characterizing different disease activity status of IBD patients. Measurement of serum 25(OH)D in IBD patients may be warranted. 25(OH)D supplementation in deficient IBD patients is recommended.

IL-28B-SNP predicts the outcome for chronic HCV genotype-1 patients receiving protease inhibitor-based triple-therapy. The predictive value varies between the different protease inhibitors.

Background: Studies of serum vitamin D (Vit-D) levels in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor-alpha (anti-TNF-α) agents are scarce. The conjunction of Vit-D as well as zinc levels and anti-TNF-α-trough concentrations (TC) has not yet been explored. Objectives: To determine the association of serum Vit-D, zinc and C-reactive protein (CRP) levels with clinical and biochemical remission and a possible correlation with serum TC and antibody levels of anti-TNF-α. Methods: Serum Vit-D and zinc levels as well as Infliximab (IFX) and Adalimumab (ADA) TC during the maintenance phase of treatment were measured in 112 IBD patients. Statistical analysis were performed for clinical and biochemical remission. Results: Vit-D and zinc deficiency were detected in 58 and 4.5% of the patients respectively. In IFX-treated patients, IFX-TC, Vit-D and CRP levels were associated independently with clinical remission with an OR of 20 (95% CI 1.3-333, p = 0.03), 1.3 (95% CI 1.1-1.7, p = 0.02) and 0.4 (95% CI 0.2-0.8, p = 0.01) respectively. Serum IFX-TC and Vit-D levels correlated positively (r = 0.39, p = 0.001), while serum IFX-TC and CRP levels showed an inverse correlation (r =-0.43, p < 0.001). Only IFX-TC associated independently with biochemical remission with a threshold of 3.1 µg/mL. In ADA-treated patients, ADA-TC associated independently with clinical and biochemical remission with an OR of 2.5 (95% CI 1.1-5.0, p = 0.04) and 1.3 (95% CI 1.1-1.4, p = 0.03) respectively. The serum zinc level was associated neither with clinical nor with biochemical remission in either cohort. Conclusions: Our results indicate that serum Vit-D level may be a predictive marker in addition to drug trough levels in IBD patients treated with IFX. Furthermore, due to the correlation between serum IFX and Vit-D levels, Vit-D substitution should be conducted in patients with low Vit-D levels.

BackgroundFaecal calprotectin (FC) seems to be the best available biomarker for the detection of intestinal inflammation in patients with inflammatory bowel disease (IBD). The aim of this study is to clarify whether the measurement of FC has changed the number of ultrasound and endoscopic procedures, drug modifications, as well as FC re-measurements in IBD patients.MethodsThis retrospective study included 242 IBD patients with available FC values (case cohort) and 46 patients without an available FC value (control cohort). Clinical consequences such as carrying out abdominal ultrasound, endoscopy, drug modification or FC re-measurement at the next ambulatory presentation or during in-patient stay were collected. Statistical analysis was performed to determine the association between clinical decision-making and patient’s characteristics, especially FC value.ResultsOverall, 192 (67%) clinical consequences were noted in both cohorts. In the case cohort 174 (91%) implications were noted compared to 18 (9%) in the control cohort (P < 0.001). In the case cohort, significantly more clinical consequences were detected in patients with Crohn’s disease (CD) as well as in ulcerative colitis (UC) patients with a FC value > 250 mg/Kg than in patients with a value of ≤ 250 mg/Kg. In CD patients with high FC values significantly increased numbers of abdominal ultrasounds, endoscopies and FC re-measurements were noted. In UC patients with high FC values significantly increased numbers of abdominal ultrasounds, drug modifications and FC re-measurements were noted.ConclusionMeasurement of FC may alter physician’s clinical decision-making in IBD patients beside other clinical and diagnostic parameters. Further prospective and survey studies are warranted to evaluate the influence of FC measurement in the daily clinical decision-making.

BackgroundConcurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality.MethodsA retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome.ResultsThe sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status.ConclusionsIn addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.