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

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

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

Characteristics of the 199 patients in the study.

<p>BMI, body mass index; AST, aspartate transaminase; ALT, alanine aminotransferase; TG, triglycerides; APRI, aspartate transaminase to platelets ratio index; HA, hyaluronic acid; 7S collagen, collagen type IV; GSD, glycogen storage disease; PSC, primary sclerosing cholangitis; NS, not significant</p><p>The 3 groups were compared by using the Kruskal–Wallis test for continuous variables. When the Kruskal–Wallis test identified a significant difference (<i>P</i> < 0.05), the Mann–Whitney U test with Bonferroni correction was used to identify the source of difference. Two-sided <i>P</i>-values < 0.05 were considered significant.</p><p>*Results are expressed as mean ± 1 SD.</p><p>Characteristics of the 199 patients in the study.</p

Supplementary Tables -Supplemental material for Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C

<p>Supplemental material, Supplementary Tables for Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C by Masaru Enomoto, Yoshihiro Ikura, Akihiro Tamori, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Hideki Fujii, Sawako Uchida-Kobayashi, Hiroyasu Morikawa, Yoshiki Murakami and Norifumi Kawada in United European Gastroenterology Journal</p

Clinical features of patients at the second liver biopsy after SVR.

<p>Clinical features of patients at the second liver biopsy after SVR.</p

Clinical features of the patients at Pre-IFN treatment.

<p>Clinical features of the patients at Pre-IFN treatment.</p

Collagen deposition and the presence of α-SMA-positive cells in liver tissue with HCC.

<p>Sirius red staining (A and B), α-SMA immunohistochemistry (C and D), CYGB immunofluorescence staining (E and F), α-SMA immunofluorescence staining (G and H), merged image of CYGB and α-SMA (I and J) before IFN treatment and after SVR from Case 2. Insets show enlarged views of CYGB/α-SMA-double-positive cells. Bar, 50 μm. P, portal vein.</p