Association of nonalcoholic fatty liver disease with small intestine bacterial overgrowth in obese children.

OBJECTIVE: Introduction: In recent years, NAFLD is considered as the key of the so-called metabolic inflammation, in which the intestinal microbiota plays an important role. The aim: To determine the effect of small intestine bacterial overgrowth on the liver structural and functional parameters in children with obesity and overweight. PATIENTS AND METHODS: Materials and methods: The object of the study was 89 children with obesity/overweight. Depending on the presence of SIBO based on the results of the hydrogen breath test with glucose, the patients were divided into 2 groups: first (I) consisted of 31 children with SIBO, the second (II) included 58 children without SIBO. All the patients under study performed a general blood analysis and a biochemical blood test, immuno-enzyme test method with insulin level determination HOMA index calculation. For diagnostics of the liver steatosis, transient elastography with the CAP (controlled attenuation parameter) function was carried out using FibroScan® 502 touch (Echosens, Paris, France). RESULTS: Results: According to fibroscan data, the presence of SIBO in obese children can lead to raise of CAP level; liver steatosis was diagnosed in 22 patients (70.9%) of the 1st group and 24 patients (41.4%) of the 2 group (p<0,05). We found significant differences in the the ratio of neutrophils and lymphocytes (NLR) (p <0.05). The average glucose level and HOMA index were significantly higher in SIBO group (p<0,05). The analysis of risk factors of SIBO showed that metabolic syndrome and NAFLD as the risk factors for SIBO development (p<0,05). CONCLUSION: Conclusions: SIBO has an effect on the structural and functional characteristics of the liver resulting in higher insulin and glucose level, higher NLR level and greater prevalence of NAFLD.

Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study.

OBJECTIVE: Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. DESIGN: In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure-response relationship and histological improvement. RESULTS: 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108-235 µg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. CONCLUSIONS: Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose-response studies are warranted. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00656890.

The Role of FXR-Signaling Variability in the Development and Course of Non-Alcoholic Fatty Liver Disease in Children.

INTRODUCTION: Genetic mechanisms among many other factors play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD). The farnesoid X-receptor (FXR) regulates the expression of target genes involved in metabolic and energy homeostasis, so it can be assumed that genetic variations within the NR1H4 gene, encoding FXR, can affect the development or progression of associated diseases, including NAFLD. THE AIM: To study the association of SNP rs11110390 NR1H4 gene with the probability of development and course of NAFLD in children. MATERIALS AND METHODS: 76 children aged 9-17 years and overweight were examined. According to controlled attenuated parameter (CAP) measurement (Fibroscan®502touch) children were divided into 2 groups: group 1 consisted of 40 patients with NAFLD, group 2 was composed by 36 patients without hepatic steatosis. According to genetic testing children were divided into 3 subgroups - children with CC-, CT-, TT-genotype SNP rs11110390 NR1H4 gene. RESULTS: The frequency of TT-genotype SNP rs11110390 NR1H4 gene detection in children with NAFLD was 17.5% versus 2.8% in the control group (p NR1H4 gene the liver stiffness (p NR1H4 (p NR1H4 is associated with an increased probability of NAFLD development in children. An increase in the steatosis degree and liver stiffness in combination with increased taurine-conjugated bile acids fractions in the hepatic and gallbladder's bile, shift in cytokine balance due to a decrease in IL-10 level in children with TT-genotype SNP rs11110390 NR1H4 were observed.