Kai‐Chi Chang

Background: The rising prevalence of severe obesity among children and adolescents poses a major public health challenge.Purpose: In this study, we examined the differences in body composition and physical fitness between obese and severely obese Asian youth and evaluated their responses to a customized lifestyle intervention.Methods: A total of 136 overweight and obese participants (mean age, 11.5±3.0 years) were enrolled in an individualized lifestyle modification program. The participants were stratified by obesity severity, with severe obesity defined as a body mass index (BMI)-for-age ≥120% of the 95th percentile. Body composition and physical fitness were assessed at baseline and after 3 interventional stages. The results were compared between the severely obese group and nonseverely obese group, and the relationships between the changes were analyzed.Results: Among the obese participants, 46% met the criteria for severe obesity. At baseline, those with severe obesity demonstrated a lower performance percentile in the 1-minute sit-up test (22.1±25.2 vs. 47.9±28.0, P=0.002) and the standing long jump (8.5±14.6 vs. 26.8±23.2, P= 0.003) than their nonseverely obese peers. Participants in both groups showed significant reductions in body fat percentage and preserved skeletal muscle mass after the intervention. Those in the severely obese group achieved greater reductions in weight, BMI, BMI z score, and fat mass, particularly during the first 2 interventional stages, indicating a stronger response to the program.Conclusion: The severely obese youth showed poorer baseline physical fitness levels but greater improvements in key obesity-related measures following the lifestyle interventions. These findings highlight the potential benefits of early targeted interventions for this high-risk group.

Background: Biliary atresia (BA) is the leading cause of pediatric liver transplantation worldwide. However, the genetic background remains unclear in most patients. In this genome‐wide association study (GWAS), we aimed to identify genetic loci that contribute to susceptibility to BA. Methods: We recruited 189 BA patients (85 males and 104 females) and 558 non‐BA controls (275 males and 283 females) for this GWAS analysis using the Axiom Genome‐Wide TWB 2.0 Array with 686,463 single‐nucleotide polymorphisms (SNPs). The MassARRAY Sequenom analysis was then applied to validate the identified top SNPs. Results: We identified rs139120621 (odds ratio [OR] = 17.31, p = 2.78 × 10 ⁻⁹ ) at 8q22.1, which is mapped to the FLJ46284 gene, significantly correlated with BA in this Taiwanese cohort. The rs113128512 located at chromosome 4q32.1 (OR = 9.13, p = 1.30 × 10 ⁻⁶ ), and rs11193325 (OR = 1.85, p = 8.20 × 10 ⁻⁶ ) at 10q25.1 are also associated with BA. The rs113128512 is mapped to the PDGFC gene, and rs11193325 is downstream of the SORCS1 gene. Conclusions: We identified novel loci of BA susceptibility SNPs in a Taiwanese cohort by the GWAS analysis. These findings shed light on the genetic factors in the pathophysiology of BA that might be applied to the future development of therapeutic agents for BA patients.

Background and aims: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. Methods: A total of 4717 individuals aged 1–60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti‐HBs), and hepatitis B core antibody (anti‐HBc) levels were assessed. HBV viral load, genotypes and HBsAg ‘ ɑ ’ determinant variants were evaluated if indicated. Results: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti‐HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti‐HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. Conclusion: The 35‐year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Background and Aims: The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-beta induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyse the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up. Methods: Children with CHB in the immune-tolerant phase were recruited and followed longitudinally. HBx gene sequencing of infecting HBV strains was performed, and the effects of HBx mutations on the immune-tolerant phase were assessed. Restoration of the host immune response to end the immune-tolerant phase was investigated by immunoblotting, immunostaining, ELISA and reporter assays of MAVS/IFN-beta signalling in liver cell lines, patient liver tissues and the HBV plasmid replication system. Results: A total of 173 children (median age, 6.92years) were recruited. Patients carrying HBx R87G, I127V and R87G +I127V double mutations exhibited higher cumulative incidences of immune-tolerant phase breakthrough (p = .011, p = .006 and p = .017 respectively). Cells transfected with HBx R87G and I127V mutants and pHBV1.3-B6.3 replicons containing the HBx R87G and I127V mutations exhibited statistically increased levels of IFN-beta, especially under poly(I:C) stimulation or Flag-MAVS cotransfection. HA-HBx wild-type interacted with Flag-MAVS and enhanced its ubiquitination, but this ability was diminished in the R87G and 1127V mutants. Conclusions: HBx suppresses IFN-beta induction. R87G and 1127V mutation restored IFN-beta production by preventing MAVS degradation, contributing to curtailing the HBV immune-tolerant phase in CHB patients.

Gastroesophageal flap valve (GEFV) endoscopic grading is reported to be associated with gastroesophageal reflux disease (GERD) in adults; however its role in pediatric groups remains unknown. This study aimed to investigate the significance of GEFV grading and the associations to multichannel intraluminal impedance and pH monitoring (MII-pH) in children with GERD. A total of 48 children with GERD symptoms who received esophagogastroduodenoscopy and MII-pH monitoring were enrolled. The degree of GEFV was graded from I to IV according to the Hill classification, and classified into two groups: normal GEFV (Hill grades I and II), and abnormal GEFV (Hill grades III and VI). Endoscopic findings and MII-pH monitoring were analyzed among the groups. Thirty-six patients had normal GEFV while 12 had abnormal GEFV. The presence of erosive esophagitis was significantly more common in the patients with abnormal GEFV (p = 0.037, OR 9.84, 95% CI 1.15–84.42). Pathological acidic gastroesophageal reflux (GER) determined by MII-pH was more prevalent in the patients with loosened GEFV geometry (p = 0.01, OR 7.0, 95% CI 1.67–27.38). There were significant positive correlations between GEFV Hill grading I to IV and the severity of erosive esophagitis (r = 0.49, pr = 0.37, p = 0.009), percentage of total acid reflux (r = 0.3284, p = 0.023), and DeMeester score (r = 0.36, p = 0.01) detected by pH monitoring. In the impedance study, GEFV Hill grading also positively correlated to median number of acid reflux events (r = 0.3015, p = 0.037). GEFV dysfunction highly associated with acid GER and severe erosive esophagitis. An abnormal GEFV is a sign of acid GER in children.