Profiles and results for 122 children successfully evaluated by transient elastography.

<p>Profiles and results for 122 children successfully evaluated by transient elastography.</p

Distributions of liver stiffness measurement (LSM; left) and controlled attenuation parameter (CAP; right) values with age.

<p>LSM was positively correlated with age (ρ = 0.411), whereas CAP was not (ρ = 0.179). Correlations between age and LSM or CAP were evaluated by using Spearman’ s rank correlation coefficient (ρ). Spearman’s ρ values >0.4 were considered indicative of a positive correlation.</p

Measurement completion rates (MCRs) in 138 children evaluated by transient elastography with an M probe.

<p>Measurement completion rates (MCRs) in 138 children evaluated by transient elastography with an M probe.</p

Transient Elastography-Based Liver Profiles in a Hospital-Based Pediatric Population in Japan

<div><p>Background & Aims</p><p>The utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children.</p><p>Methods</p><p>FibroScan examinations were performed in pediatric patients (age, 1–18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥90%), non-obese healthy controls, and non-obese patients with liver disease.</p><p>Results</p><p>Among 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3–17.6 yr; 115 male). CAP values (mean±SD) were higher in the obese group (n = 52, 285±60 dB/m) compared with the liver disease (n = 40, 202±62, <i>P</i><0.001) and the control (n = 107, 179±41, <i>P</i><0.001) group. LSM values were significantly higher in the obese group (5.5±2.3 kPa) than in the control (3.9±0.9, <i>P</i><0.001), but there were no significant differences in LSM between the liver disease group (5.4±4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups.</p><p>Conclusions</p><p>Childhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children.</p></div

Comparison of results from FibroScan, liver biopsy, and abdominal ultrasonography (AUS).

<p>a and b. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) values from FibroScan evaluations were compared with histologic fibrosis stage and steatosis grade. Liver biopsy was performed in 8 pediatric patients, in which the underlying disease was simple obesity in 4 patients, type C hepatitis in 2 patients, type B hepatitis associated with obesity in 1 patient, and liver transplantation for treatment of congenital biliary atresia in 1 patient. Among the 5 obese patients, four patients were diagnosed with NASH, and the remaining patient was diagnosed with simple steatosis. a. Correlation between LSM value and histologic fibrosis stage. LSM was highly correlated with fibrosis stage (Spearman’s <i>ρ</i> = 0.920). b. Correlation between CAP value and histologic steatosis grade. CAP value was highly correlated with steatosis grade (<i>ρ</i> = 0.792). c. Correlation between CAP and fatty liver infiltration score calculated according to AUS findings. CAP was highly correlated with AUS fatty liver infiltration score (<i>ρ</i> = 0.713).</p

Potential Roles of CCR5⁺ CCR6⁺ Dendritic Cells Induced by Nasal Ovalbumin plus Flt3 Ligand Expressing Adenovirus for Mucosal IgA Responses

<div><p>We assessed the role of CCR5⁺/CCR6⁺/CD11b⁺/CD11c⁺ dendritic cells (DCs) for induction of ovalbumin (OVA)-specific antibody (Ab) responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL) showed early expansion of CCR5⁺/CCR6⁺/CD11b⁺/CD11c⁺ DCs in nasopharyngeal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs). Subsequently, this DC subset became resident in submandibular glands (SMGs) and nasal passages (NPs) in response to high levels of CCR-ligands produced in these tissues. CD11b⁺/CD11c⁺ DCs were markedly decreased in both CCR5^−/− and CCR6^−/− mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR) and CCR5^−/− or CD11c-DTR and CCR6^−/− mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA )Ab responses in saliva and nasal washes. These results suggest that CCR5⁺CCR6⁺ DCs play an important role in the induction of Ag-specific SIgA Ab responses.</p> </div

Correlation between LSM and CAP values.

<p>LSM was positively correlated with CAP in the obese group (Spearman’s ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) group.</p

Age distribution of the patients examined by using FibroScan.

<p>A total of 214 children and adolescents (age, 1.3–17.6 years; 121 male) were examined by using FibroScan. A total of 201 patients (93.9%; median age, 11.5 years; range, 1.3–17.6 years) (black bars) were examined successfully; the evaluation was unsuccessful in the remaining 13 patients (6.1%; median age, 13.1 years; range, 2.0–17.2 years) (gray bars) due to excessive thickness of subcutaneous adipose tissue in 5 obese children (BMI percentile [mean ± 1 SD], 99.6 ± 2.2), poor cooperation in 4 young children (2.0, 3.7, 4.0, and 6.2 years), and no obvious reason in 4 non-obese and cooperative children.</p

Diagram of the study population selection process.

<p>Patients who were examined by using FibroScan at a success rate of greater than 60% with 10 valid measurement and an interquartile range (IQR) of 30% or less than 30% of the median LSM value were analyzed for the study. Patients whose body mass index (BMI) was at the 90^th percentile or higher and without underlying liver diseases were included in the obese group. Patients whose BMI was lower than the 90^th percentile were divided into 2 groups: control group or liver disease group. The control group was defined as having normal serum liver enzyme levels, an aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score below 0.5, a normal-appearing liver on abdominal ultrasonography, and no episodes of liver disease. The remaining patients were included in the liver disease group.</p

OVA-specific Ab responses in systemic and mucosa-associated lymphoid tissues of chimera mice which lack CCR5- or CCR6-expressing DCs (Figure S1).

<p>(A and C) CD11c-DTR, CD11c-DTR/C57BL/6, CD11c-DTR/CCR5^−/− and CD11c-DTR/CCR6^−/− mice were injected with DT via the intraperitoneal route 6 h before each nasal immunization (three times at weekly intervals with OVA plus Ad-FL). CD11c-DTR/C57BL/6 chimera mice given the DT injection served as positive controls. (B) CD11c-DTR/C57BL/6, CD11c-DTR/CCR5^−/−, CD11c-DTR/CCR6^−/− and normal C57BL/6 were nasally immunized three times at weekly intervals with OVA plus Ad-FL without DT injection. (A and B) Seven days after the last immunization, levels of SIgA anti-OVA Abs in saliva, SIgA and IgG Abs in NWs, and IgA, IgG and IgM Abs in plasma were determined by OVA-specific ELISA. (C) MNCs from NPs, SMGs and spleens were isolated 7 days after the last immunization and subjected to OVA-specific ELISPOT assay to determine the numbers of IgA, IgG and IgM AFCs. The values shown are the mean ± SEM taken from five separate experiments with a total of 25 mice in each experimental group. The data for controls were obtained from two separate experiments which consisted of 6 mice for each experiment. The ELISA and ELISPOT data for spleen represented the Ab responses from 12 individual mice for controls and 25 individual mice for experimental groups. MNCs from SMGs and NPs were pooled from 2 or 3 mice and subjected to OVA-specific ELISPOT assays. N.D. means that O.D. values were not detected. (A and C) *<i>p</i><0.05 when compared with DT treated, CD11c-DTR/C57BL/6 chimera mice nasally immunized with OVA plus Ad-FL. (B) No significant differences were detected when compared with normal C57BL/6 mice.</p