Search

Summary: Background: Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022. Methods: We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term “autoimmune hepatitis” in combination with “incidence,” “prevalence,” or “trend.” Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings: A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01–1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42–18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970–1999; 9.95 [4.77–15.13], I2 = 95·58% versus 2015–2022; 27.91 [24.86–30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias. Interpretation: AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa. Funding: National Research Foundation of Korea.

Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.

Abstract Background An elevated alanine aminotransferase (ALT) level is a surrogate marker of non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in adolescents. The majority of previous NAFLD studies in adolescents were performed in selected obese populations or had a cross-sectional design without a time-trend analysis. The purpose of this study was to estimate the prevalence and time trends of elevated ALT levels in a general adolescent population and to identify factors associated with ALT elevation. Methods We analysed data of adolescent participants (aged 10–18 years) from the Korean National Health and Nutrition Examination Survey 2001–2014, a representative sample of the general population in South Korea. Suspected NAFLD was defined as ALT elevation (> 30 U/L) without hepatitis B surface antigen. In all statistical analyses, sampling weight- and design-based data were used. Results ALT was elevated in 5.3% (standard error: 0.3%) of the study population of adolescent participants (N = 8455). No significant trends were found from 2001 to 2014 in the prevalence of elevated ALT among male and female adolescents. In multiple logistic regression analysis, elevated ALT was independently associated with sex (odds ratio [OR] male versus female 4.5; 95% CI, 3.3-6.2), obesity (OR 7.6; 95% CI, 5.3-11.0), and truncal obesity (OR 2.5; 95% CI, 1.8-3.5). Furthermore, male sex, obesity, truncal obesity and high household income level were associated with log-transformed ALT levels in multiple regression analysis. Conclusions In Korean adolescents of both genders, the prevalence of elevated ALT levels was stable from 2001 to 2014. This study has revealed that sex, obesity, truncal obesity and household income level are associated with ALT elevation in adolescents.

Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Background: The interleukin 23 receptor gene (IL23R) is strongly associated with Crohn's disease (CD). It is unknown whether genetic variations in IL23R determine susceptibility for pediatric CD in Asian populations. Here, we investigated the association between IL23R variants and CD in Korean children.Methods: Four single nucleotide polymorphisms (SNPs) of IL23R [rs76418789 (G149R), rs1004819, rs7517847, and rs1495965] were genotyped in 141 children with CD and 150 controls using DNA direct sequencing. The risk allele and genotype frequencies were compared between patients and controls. The association between clinical phenotypes and genotypes of patients was also analyzed.Results: Two IL23R SNPs, rs76418789 (G149R), and rs1495965, were associated with CD in Korean pediatric patients as defense and risk loci, respectively. The odds ratio (OR) for rs76418789 (G149R) and rs1495965 was 0.409 (95% confidence interval [CI], 0.177–0.944; p = 0.031) and 1.484 (95% CI, 1.070–2.059; p = 0.018), respectively. Patients with the homozygous G allele of rs1495965 showed higher CD risk than those with other genotypes (GG vs. AA: OR, 2.256; 95% CI, 1.136–4.478; p = 0.019; GG vs. GA+AA: OR, 2.000; 95% CI, 1.175–3.404; p = 0.010). Additionally, they were more likely to have relatively invasive disease behavior of stenosis and/or penetration than simple inflammation (OR, 2.297; 95% CI, 1.065–4.950; p = 0.032).Conclusions: This is the first study reporting IL23R variants in Asian pediatric patients with CD. IL23R was significantly associated with Korean pediatric CD, and the rs1495965 may influence the clinical features of CD in Korean children.

PurposeDiencephalic syndrome is an uncommon cause of failure to thrive in early childhood that is associated with central nervous system neoplasms in the hypothalamic-optic chiasmatic region. It is characterized by complex signs and symptoms related to hypothalamic dysfunction; such nonspecific clinical features may delay diagnosis of the brain tumor. In this study, we analyzed a series of cases in order to define characteristic features of diencephalic syndrome.MethodsWe performed a retrospective study of 8 patients with diencephalic syndrome (age, 5-38 months). All cases had presented to Seoul National University Children's Hospital between 1995 and 2013, with the chief complaint of poor weight gain.ResultsDiencephalic syndrome with central nervous system (CNS) neoplasm was identified in 8 patients. The mean age at which symptoms were noted was 18±10.5 months, and diagnosis after symptom onset was made at the mean age of 11±9.7 months. The mean z score was -3.15±1.14 for weight, -0.12±1.05 for height, 1.01±1.58 for head circumference, and -1.76±1.97 for weight-for-height. Clinical features included failure to thrive (n=8), hydrocephalus (n=5), recurrent vomiting (n=5), strabismus (n=2), developmental delay (n=2), hyperactivity (n=1), nystagmus (n=1), and diarrhea (n=1). On follow-up evaluation, 3 patients showed improvement and remained in stable remission, 2 patients were still receiving chemotherapy, and 3 patients were discharged for palliative care.ConclusionDiencephalic syndrome is a rare cause of failure to thrive, and diagnosis is frequently delayed. Thus, it is important to consider the possibility of a CNS neoplasm as a cause of failure to thrive and to ensure early diagnosis.

Purpose: Non-alcoholic fatty liver disease (NAFLD) ranges in severity from simple steatosis to steatohepatitis. Early detection of NAFLD is important for preventing the disease from progressing to become an irreversible end-stage liver disease. We developed a nomogram that allows for non-invasive screening for NAFLD in obese children. Methods: Anthropometric and laboratory data of 180 patients from our pediatric obesity clinic were collected. Diagnoses of NAFLD were based on abdominal ultrasonographic findings. The nomogram was constructed using predictors from a multivariate analysis of NAFLD risk factors. Results: The subjects were divided into non-NAFLD (n=67) and NAFLD groups (n=113). Factors, including sex, body mass index, abdominal circumference, blood pressure, insulin resistance, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (ΔGT), uric acid, triglycerides, and insulin, were significantly different between the two groups (all p<0.05) as determined using homeostatis model assessment of insulin resistance (HOMA-IR). In our multivariate logistic regression analysis, elevated serum ALT, ΔGT, and triglyceride levels were significantly related to NAFLD development. The nomogram was established using ΔGT, uric acid, triglycerides, HOMA-IR, and ALT as predictors of NAFLD probability. Conclusion: The newly developed nomogram may help predict NAFLD risk in obese children. The nomogram may also allow for early NAFLD diagnosis without the need for invasive liver biopsy or expensive liver imaging, and may also allow clinicians to intervene early to prevent the progression of NAFLD to become a more advanced liver disease. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore changes in clinical epidemiology and genotype distribution and their association among hospitalized children with rotavirus gastroenteritis after the introduction of vaccines.Methods: Between November 2010 and October 2014, hospitalized children with acute gastroenteritis were enrolled. Rotavirus genotypes were confirmed through reverse transcription-polymerase chain reaction (RT-PCR), semi-nested PCR, and sequencing. Clinical information including vaccination status and the modified Vesikari scores were collected.Results: Among 179 children with rotavirus infection, nineteen (10.6 %) were completely vaccinated. During the study period, the number of children between three and 23 months of age decreased significantly compared to the number of children older than 24 months of age (P = 0.010), who showed lower diarrhea severity (duration, P = 0.042; frequency, P = 0.021) but higher vomiting severity (P = 0.007, 0.036) compared to the former. Vaccination status was also significantly associated with lower vomiting severity after adjustment for age (frequency only, P = 0.018). The predominant genotypes were G2P[4] (18.4 %), G1P[8] (14.5 %), and G1P[4]P[8] (12.8 %), and the prevalence of genotypes with uncommon and mixed combinations was more than 50 %. Children infected with G2P[4] strains tended to be older (P = 0.005) and had more severe vomiting (P = 0.018, 0.006) than those with G1P[8].Conclusions: Increase in age of infected, hospitalized children was accompanied by change in clinical severity during 2011-2014 after the introduction of vaccines in Seoul. Clinical severity was also associated with vaccination status and genotype. Long-term large scale studies are needed to document the significance of the increase in genotypes of uncommon and mixed combinations. [ABSTRACT FROM AUTHOR]

Purpose: Parenteral nutrition (PN) not only provides nutritional support but also plays a crucial role in the treatment of children with intestinal failure. The aim of this study was to evaluate the clinical significance and clinical outcomes of long-term PN. Methods: Retrospective cohort study was conducted using the medical records of patients treated at Seoul National University Children's Hospital. This study included 19 patients who received PN for over six months. Most patients received home PN. Results: The indications for PN included short bowel syndrome, chronic intestinal pseudo-obstruction, and intractable diarrhea of infancy. The median age of PN initiation was 1.3 years, and the median treatment duration was 2.9 years. Two patients were weaned from PN; 14 continued to receive PN with enteral feedings; and 3 patients died. The overall survival rates at 2 and 5 years were 93.3% and 84.0%, respectively. The incidence of catheter-related bloodstream infections was 2.7/1,000 catheter-days and was associated with younger age at PN initiation and lower initial height Z-score. Six patients developed catheter-related central vein thrombosis, with an incidence of 0.25/1,000 catheter-days. Eleven patients experienced PN-associated liver disease (PNALD), and one patient underwent multi-visceral transplant. The patients with PNALD exhibited lower final heights and body weight Z-scores. All patients experienced micronutrient deficiencies transiently while receiving PN. Conclusion: PN is an important and safe treatment for pediatric intestinal failure. PNALD was linked to final anthropometric poor outcomes. Micronutrient deficiencies were common. Anthropometric measurements and micronutrient levels must be monitored for successful PN completion. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to investigate the clinical features and outcome of eosinophilic gastroenteritis (EGE) in children. Methods: Our study enrolled 24 children who were diagnosed with EGE from 1993 to 2014 at the Department of Pediatrics, Seoul National University Children's Hospital. The patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Results: The mean age at diagnosis was 5.3 years. Most patients had gastrointestinal symptoms including diarrhea (54.2%) and abdominal pain (45.8%). Peripheral eosinophilia was present in 91.7% of the patients. Thirteen patients (54.2%) showed anemia, and 15 patients (62.5%) had hypoalbuminemia. EGE was classified as mucosal, subserosal, or muscular in 75.0%, 20.8%, and 4.2% of cases, respectively. Three patients showed gastroduodenal ulcers upon endoscopic analysis. A history of allergy was reported in 13 patients, including atopic dermatitis, allergic rhinitis, and asthma. Five patients (20.8%) improved with food restrictions. Among the 19 patients treated with steroids, 11 (57.9%) discontinued steroid treatment without subsequent relapse, 4 (21.1%) relapsed after ceasing steroid treatment, and 4 (21.1%) showed no response to steroids. Two patients who were resistant to steroids underwent therapeutic surgery. The presence of gastroduodenal ulcers was significantly associated with relapse and steroid resistance. Conclusion: A high suspicion of EGE is warranted when children have nonspecific gastrointestinal symptoms and peripheral eosinophilia. Most patients improved with food restrictions or steroid treatment, although one-third of patients showed a relapse or steroid resistance. [ABSTRACT FROM AUTHOR]

Purpose: Crigler-Najjar syndrome type II (CN-2) is characterized by moderate non-hemolytic unconjugated hyper-bilirubinemia as a result of severe deficiency of bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The study investigated the mutation spectrum of UGT1A1 gene in Korean children with CN-2. Methods: Five Korean CN-2 patients from five unrelated families and 50 healthy controls were enrolled. All five exons and flanking introns of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced. Results: All children initially presented with neonatal jaundice and had persistent indirect hyperbilirubinemia. Homozygous p.Y486D was identified in all five patients. Three patients had an associated homozygous p.G71R and two a heterozygous p.G71R. The allele frequency of p.Y486D and p.G71R in healthy controls was 0 and 0.16, respectively. No significant difference in mean serum bilirubin levels was found between homozygous carriers of p.G71R and heterozygous carriers. Conclusion: The combination of homozygous p.Y486D and homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be screened for the mutation analysis of UGT1A1 in Korean CN-2 patients. [ABSTRACT FROM AUTHOR]

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. [ABSTRACT FROM AUTHOR]

We evaluated the relationship between mean platelet volume (MPV) and characteristics of 10,577 cord blood (CB) units in a public CB bank in Korea. Blood group O has the highest MPV (P = 0.002). MPV correlated with CB volume (r = 0.121), Hb (r = 0.377), WBC (r = 0.111), TNCs (r = 0.110), CD34+ cell (r = 0.174), CD34+ cells/TNCs (r = 0.157), gestational age (r = -0.102), and birth weight (r = 0.023); (P < 0.001 in all). MPV may be one of the useful decision parameters of process priority in CB bank. [ABSTRACT FROM AUTHOR]

Wharton's jelly is not only one of the most promising tissue sources for mesenchymal stem cells (MSCs) but also a source of natural growth factors. To prove that we can get both natural growth factors and MSCs from Wharton's jelly, we compared cellular characteristics and the level of basic fibroblast growth factor (bFGF) from samples using the explant culture method to those derived from the traditional enzymatic culture method. The levels of bFGF were 27.0 ± 11.7 ng/g on day 3, 15.6 ± 11.1 ng/g on day 6, and decreased to 2.6 ± 1.2 ng/g on day 14. The total amount of bFGF released was 55.0 ± 25.6 ng/g on explant culture. Compared with the traditional enzymatic digestion method, the explant culture method showed a tendency to release higher levels of bFGF in supernatant media for the first week of culture, and the higher cellular yield at passage 0 (4.89 ± 3.2 × 105/g versus 1.75 ± 2.2 × 105/g, P = 0.01). In addition, the genes related to mitosis were upregulated in the explant-derived MSCs. [ABSTRACT FROM AUTHOR]

Antibiotic-associated diarrhea due to Clostridium difficile (CDAD) is thought to reflect colonization of a disrupted microbial community by the pathogen. We profiled the fecal microbiota of patients with CDAD (both initial and recurrent episodes) by culture-independent phylogenetic analysis of 16S rRNA-encoding gene sequences. Compared with those from control subjects and patients with an initial episode, the fecal communities in patients with recurrent CDAD were highly variable in bacterial composition and were characterized by markedly decreased diversity. Preservation and restoration of the microbial diversity could represent novel strategies for prevention and treatment of recurrent CDAD, which is often recalcitrant to existing therapies. [ABSTRACT FROM AUTHOR]

Presents a case of patients with acute symptomatic spinal epidural cerebrospinal fluid leakage after a diagnostic lumbar puncture who lacked these risk factors. Case histories; Complications of lumbar punctures; Mechanism of postlumbar puncture syndrome; Coagulation test results; Relation of the risk of postdural puncture headache to the diameter of the needle used.

Background/Aims Pediatric autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea in children. Through this study, we present seven cases of pediatric patients diagnosed with AIE. Our study aids in understanding the clinical and genetic characteristics of this rare genetic condition and the considerations in its management. Methods From December 1996 to September 2019, seven cases who were diagnosed as AIE in Seoul National University Children's Hospital were retrospectively analyzed. The clinical sources of all AIE cases were reviewed, including electronic medical records, histopathologic material, radiologic images, and laboratory findings. Results Initial symptoms were diarrhea (in six children) and hematochezia (in one patient). Later, all patients had severe diarrhea which started in the early months of life. Among the five patients tested on gene studies, forkhead box P3 (FOXP3) mutations were identified in four patients, and all of them were males. All patients initially received steroid treatment. Patients with a partial and transient response were considered for alternative agents. Three patients (42.9%) remained in remission under tacrolimus monotherapy, one patient (14.3%) with tacrolimus and prednisolone combination therapy, one patient (14.3%) with tacrolimus, prednisolone, and cyclosporine combination therapy, one patient (14.3%) had died of fulminant hepatitis, and one patient (14.3%) had died of septic shock. All patients were treated with tacrolimus for more than 1 year. Estimated glomerular filtration rate (eGFR) decreased in six patients (85.7%) and increased in one patient (14.3%). Conclusions In this study, all patients treated with tacrolimus showed amelioration of symptoms. However, histological characteristics did not correlate with symptom improvement. Therefore, the efficacy of treatment can be assessed by symptoms and frequent endoscopic biopsies are not required. For long-term use of tacrolimus, close observation of eGFR is recommended to detect nephrotoxicity early. [ABSTRACT FROM AUTHOR]

Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by alteration of the adenosine triphosphatase 7B gene. It is rare to diagnose WD below the age of three years. Molecular genetic testing is one of the most important diagnostic methods and may confirm the diagnosis in equivocal cases. We report a case of a 9-mo old boy with WD who presented as chronic hepatitis. Genetic analysis showed compound heterozygotes of p.G1186S and c.4006delA.