Association between adeno-associated virus 2 and severe acute hepatitis of unknown etiology in Japanese children.

INTRODUCTION: Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022. METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR. RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases. CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.

Integration of Viral Genome to Human Genomic DNA in Nails of Patients with Chronic Hepatitis B Virus Infection.

Introduction: Hepatitis B virus (HBV) DNA and cytomegalovirus (CMV) DNA can be detected in patient genomes. However, it remains unknown whether viral DNA can be integrated into host genomic DNA and detected in fingernails. Methods: Nails from patients with chronic HBV infection were investigated. A total of 60 patients (male/female = 20/40, age range from 2 years to 59 years, median 15 years) were included in this study. The viral DNA levels of herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella-zoster virus (VZV), Epstein‒Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7), and HBV in nails were measured with real-time PCR. Viral DNA integration into host genomic DNA was analyzed by capture-based next-generation sequencing (NGS). Moreover, virus/host chimeric sequences, which were detected by capture-based NGS, were confirmed by Sanger sequencing. Results: Of the 60 patients, 37 (62%) were positive for nail HBV DNA. All 60 patients were negative for nail HSV-1, HSV-2, VZV, CMV, EBV, or HHV-6 DNA. However, three patients were positive for nail HHV-7 DNA. All three nail HHV-7-positive patients were also positive for nail HBV DNA. The three nail samples that were positive for both HBV and HHV-7 DNA were used for viral integration analysis by capture-based NGS. One of the three nail samples showed HBV/host chimeric sequences. In addition, all three nail samples showed HHV-7/host chimeric sequences. However, these viral integration breakpoints were not confirmed by Sanger sequencing. Conclusions: Viral integrations were detected in nails by capture-based NGS. However, Sanger sequencing did not confirm any virus/host chimeric sequences. This study could not show reliable evidence of viral integration in nails.

Clinicopathologic Features, Genetics, Treatment, and Long-Term Outcomes in Japanese Children and Young Adults with Benign Recurrent Intrahepatic Cholestasis: A Multicenter Study.

BACKGROUND: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. METHODS: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. RESULTS: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. CONCLUSIONS: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory.

Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function.

Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene is an inborn error of immunity presenting with autoimmunity and lymphoproliferation. Symptoms can vary widely, and no effective treatment has been established. This study investigated the efficacy of Janus kinase (JAK) inhibitors (JAKi) in patients with STAT3-GOF. Four patients were enrolled and their clinical symptoms before and after the initiation of treatment with JAKi were described. A cell stimulation assay was performed using Epstein-Barr virus transformed lymphoid cell lines (EBV-LCLs) that were derived from the patients with STAT3-GOF. The patients presented with various symptoms, and these symptoms mostly improved after the initiation of JAKi treatment. Upon interleukin-6 stimulation, the EBV-LCLs of patients showed enhanced STAT3 phosphorylation compared with those of the EBV-LCLs of healthy controls. In conclusion, four Japanese patients with STAT3-GOF were successfully treated with JAKi. JAKi ameliorated various symptoms and therefore, the use of JAKi could be an effective treatment option for patients with STAT3-GOF.

Clinical features of pediatric eosinophilic gastroenteritis.

BACKGROUND: No study has analyzed more than100 cases of eosinophilic gastroenteritis (EGE) in children in a single center. We aimed to describe the clinical features of pediatric EGE. METHODS: This retrospective study was conducted at a single center. Between April 2007 and December 2017, 860 children between the ages of 1 year and 15 years underwent endoscopy for gastrointestinal symptoms of unknown cause. Among them, 109 (12.7%) were diagnosed with EGE according to the diagnostic criteria for EGE developed by the research group of the Ministry of Health, Labour and Welfare of Japan for eosinophilic gastrointestinal disorder in 2015. We investigated their symptoms, comorbidities, endoscopic findings, pathological findings, treatments, and outcomes. RESULTS: Seventy-one boys (65.1%) and 38 girls (34.9%) were diagnosed with EGE. The median age at diagnosis was 11 years (range, 1-15 years). The chief complaints were abdominal pain in 83 (76.1%) and diarrhea in 26 (23.9%). Upper and lower gastrointestinal endoscopies showed normal findings in 32 patients (29.4%). The most common treatment was a combination of elimination of foods suspected of causing EGE and anti-allergic agents in 50 cases (45.9%). The outcomes were symptom disappearance in 43 patients (39.4%) and symptom improvement in 53 patients (48.6%). CONCLUSIONS: For gastrointestinal symptoms of unknown cause in children, EGE should be considered as a differential diagnosis. Although the symptoms and endoscopic findings are nonspecific, cracked mucosa may be a specific endoscopic finding for pediatric EGE. An elimination diet and/or anti-allergic drugs were effective in most patients with pediatric EGE.

Signature of chronic hepatitis B virus infection in nails and hair.

BACKGROUND: Hepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown. METHODS: We examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients' fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails. RESULTS: Of the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for ß-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients' serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were ß-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails. CONCLUSIONS: Nails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.

Clinical and Immunological Heterogeneity in Japanese Patients with Gain-of-Function Variants in STAT3.

PURPOSE: Germline loss-of-function variants in the signal transducer and activator of transcription 3 (STAT3) gene result in autosomal dominant hyper IgE syndrome, whereas somatic gain-of-function (GOF) variants in STAT3 are associated with some malignancies. In addition, germline GOF variants in STAT3 are linked to disorders involving autoimmunity and lymphoproliferation. In this study, we describe five Japanese families with germline GOF variants in STAT3, including three novel variants. We also present the clinical and immunological characteristics of these patients. METHODS: Eight patients from five families were enrolled in this study. We performed genetic and immunological analyses, and collected the associated clinical information. RESULTS: We identified five heterozygous variants in STAT3 using whole-exome sequencing and target gene sequencing. Two of these (E286G and T716M) were previously reported and three (K348E, E415G, and G618A) were novel. A STAT3 reporter assay revealed that all of the variants were GOF. However, the immunological and clinical characteristics among the patients were highly variable. CONCLUSION: Patients with STAT3 GOF variants exhibited clinical and immunological heterogeneity with incomplete penetrance.

Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: evaluation of outcomes after liver transplantation.

BACKGROUND: Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan. RESULTS: We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 18 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G > A or c.293C > T. CONCLUSIONS: MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G > A or c.293C > T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.

Biallelic Mutations in the LSR Gene Cause a Novel Type of Infantile Intrahepatic Cholestasis.

We identified biallelic pathogenic mutations in the Lipolysis-stimulated lipoprotein receptor (LSR) gene in a patient with infantile intrahepatic cholestasis. We established that mutations in the LSR gene, which encodes a protein which is critical for the formation of tricellular tight junctions in the liver, are a novel cause of pediatric cholestasis.

High Dose of Pegylated Interferon for the Treatment of Chronic Hepatitis B in Children Infected With Genotype C.

Chronic hepatitis B virus (HBV) genotype C infection is unlikely to show a good response to interferon (IFN). However, it is unknown whether a high dose of pegylated IFN (PEG-IFN) treatment would be effective for hepatitis B e antigen (HBeAg)-positive children with chronic HBV genotype C infection. Methods: HBeAg-positive children and adolescents with chronic HBV genotype C infection were eligible for this study. To increase the dose of PEG-IFN, all patients received PEG-IFN-α-2a (180 µg) without dose adjustment on the basis of body surface area for 48 weeks and were followed up for 24 weeks after the completion of treatment. Results: Thirteen patients (median age, 9 years) were enrolled prospectively for this study. One patient dropped out, and the remaining 12 patients were evaluated. Of the 12 patients, 11 received PEG-IFN of 180 µg/1.73 m2 or more (median, 287 µg/1.73 m2). Eight (67%) experienced HBeAg seroconversion, and 1 (8%) achieved hepatitis B surface antigen (HBsAg) loss at the end of follow-up. There was a significant difference in the decrease of hepatitis B surface antigen levels from the baseline to week 24 of treatment between the responders and the nonresponders. Serum cytokines and chemokines were measured in 10 patients. The levels of C-X-C motif chemokine ligand 9, 10, 11, and 13 in the responders tended to be higher than those in the nonresponders during the first 24 weeks of treatment. Conclusions: A high dose of PEG-IFN treatment was effective and safe. A decrease in the hepatitis B surface antigen level from baseline to week 24 of treatment might be a predictor of HBeAg seroconversion.

Long-term outcomes of pediatric-onset primary sclerosing cholangitis: A single-center experience in Japan.

AIM: Primary sclerosing cholangitis (PSC) is very rare in Japan. Although a large-scale cohort study of 781 pediatric-onset PSC patients in Europe and North America showed that the 5-year survival with native liver was 88%, the long-term outcomes of pediatric-onset PSC in Japan are unknown. Here, we evaluated the clinical outcomes of pediatric-onset PSC in Japan. METHODS: We carried out a retrospective cohort study with a medical records review of pediatric PSC patients diagnosed between 1986 and 2017 at a single center. The PSC diagnoses were based on cholangiography, liver histology, and biochemical findings. The patients' survival was analyzed using the Kaplan-Meier method. Prognostic factors were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. RESULTS: We identified 39 pediatric-onset PSC patients (22 boys, 17 girls). The median age at diagnosis was 9 years (interquartile range 6.0-13.5 years). The median follow-up period was 5.5 years (interquartile range 3.4-8.7 years). The phenotypes of PSC-autoimmune hepatitis, PSC-inflammatory bowel disease, and small-duct PSC were diagnosed in 13 (33.3%), 36 out of 38 (94.8%), and three (7.7%) patients, respectively. The 5-year liver transplantation-free survival of the whole cohort was 93.5%. Nine patients underwent liver transplantation, and four of these nine cases resulted in death. Both the univariate and multivariate analyses showed that the phenotype of "PSC-autoimmune hepatitis overlap" was an independent poor prognostic factor. CONCLUSIONS: The overall survival of pediatric-onset PSC in Japan was comparable to those in Western countries. The phenotype of PSC-autoimmune hepatitis was identified as a prognostic factor associated with a poorer long-term outcome.

Clinical Safety and Utility of Pediatric Balloon-assisted Enteroscopy: A Multicenter Prospective Study in Japan.

OBJECTIVES: The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan. METHODS: This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire. RESULTS: We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (P < 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE. CONCLUSIONS: This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.

Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker.

Primary sclerosing cholangitis (PSC) is a liver disease known for its frequent concurrence with inflammatory bowel disease. Dysbiosis of the gut microbiota in PSC was reported in several studies, but the microbiological features of the salivary microbiota in PSC have not been established. Here we compared the salivary microbial communities of 24 pediatric-onset PSC patients, 16 age-matched ulcerative colitis (UC) patients, and 24 healthy controls (HCs) by analyzing the bacterial 16S rRNA gene sequence data. The species-richness (α-diversity) showed no significant between-group differences, whereas the overall salivary microbiota structure (ß-diversity) showed significant differences among the three groups. Taxonomic assignment revealed that the PSC salivary microbiota were characterized by significant decreases in the abundance of Rothia and Haemophilus compared to the HC group, and significantly decreased Haemophilus and increased Oribacterium compared to the UC group. By combining the genera selected by the random forest algorithm in machine learning, followed by confirmation with 10-fold cross-validation, we were able to distinguish the PSC group from the HC group with the area under the curve (AUC) of 0.7423, and from the UC group with the AUC of 0.8756. Our results indicate the potential of salivary microbiota as biomarkers for a noninvasive diagnosis of PSC.

Usefulness of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in children with primary sclerosing cholangitis.

BACKGROUND: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) is a novel serum marker of hepatic fibrosis in adults with chronic hepatitis C. However, it remains unclear whether serum WFA+ -M2BP levels are associated with the progression of liver histology in primary sclerosing cholangitis (PSC). METHODS: Twenty-eight children and adolescents with pediatric-onset PSC (male : female patient ratio, 20:8; median age at diagnosis, 9 years) were enrolled in this study. The relation between serum WFA+ -M2BP levels and clinical characteristics was retrospectively evaluated. Moreover, receiver operating characteristic (ROC) analysis was used to determine whether serum WFA+ -M2BP levels could be a reliable marker to identify PSC patients with advanced liver histology. RESULTS: According to the Ludwig classification of liver histological stage, 28 patients were classified into the four stages. The WFA+ -M2BP level, aspartate aminotransferase (AST) to platelet ratio index (APRI), and hyaluronic acid correlated significantly with liver histological stage. Moreover, WFA+ -M2BP showed a significant positive correlation (P < 0.05) with autoimmune hepatitis overlap, AST, alanine aminotransferase (ALT), γ-glutamyltransferase, total bilirubin, immunoglobulin G, APRI, and hyaluronic acid. A ROC analysis was undertaken to distinguish the patients with advanced stage disease (stage 3-4) from those with early stage disease (stage 0-2). It showed that WFA+ -M2BP yielded the highest area under the ROC curve value (0.898) among four surrogate makers (APRI, 0.850; Fibrosis-4 index, 0.806; and AST/ALT ratio, 0.802). Moreover, WFA+ -M2BP yielded the highest sensitivity, specificity, positive predictive value, and negative predictive value among the four markers. CONCLUSIONS: Serum WFA+ -M2BP levels are useful to identify patients with advanced liver histology in pediatric PSC.

A 6-year-old girl diagnosed with mevalonate kinase deficiency who had hydrops fetalis and neonatal-onset cholestasis.

We experienced a 6-year-old girl diagnosed with mevalonate kinase deficiency (MKD) who had cholestasis, anemia, and elevated inflammatory markers in neonatal period. She was admitted to our hospital because of fever and elevated inflammatory markers at 5 years 11months of age. Without using antibiotics, the fever and the inflammatory markers were spontaneously resolved. MKD was suspected from elevated serum IgD level and the recurrent febrile attacks. The genetic test revealed heterozygous mutation of p.Leu51Phe known as causative gene of MKD and p.Met 282Thr which is the novel mutation. In addition, urinary mevalonate levels increased both in afebrile and febrile periods, and mevalonate kinase activity level was very low. Prednisolone was administered on each attack, and her febrile attack has been controlled well since she was diagnosed with MKD. Fetal edema, cholestasis, anemia, elevation of inflammatory markers in her neonatal period are considered to be complications of MKD. Recurrent fever attacks compromise quality of life in patients with MKD. Children with unexplained cholestasis and anemia in neonatal period, or recurrent fever attacks with elevated inflammatory markers should be examined for MKD.

Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott-Aldrich syndrome protein gene.

AIM: To screen primary immunodeficiency, Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD) among children with inflammatory bowel disease (IBD). METHODS: This was a single-center retrospective study. Eighteen children with IBD were investigated. We analyzed their expression of Wiskott-Aldrich syndrome protein (WASP) in lymphocytes and superoxide generation in phagocytes using flow cytometry. When the expression of WASP or superoxide generation was low or absent, we performed genetic analysis to determine the cause of this. RESULTS: Eighteen patients were classified as having ulcerative colitis (n = 10), Crohn's disease (n = 5), or IBD-unclassified (n = 3). In total, three patients revealed low expression of WASP associated with a WAS gene c.1378 C>T p.Pro460Ser mutation, which has previously been reported as a pathogenic mutation in WAS and X-linked thrombocytopenia. However, with respect to the major symptoms of WAS, none of these three patients showed either thrombocytopenia or increased susceptibility to infection, but one patient showed generalized eczema. No CGD patients were discovered in this study. CONCLUSION: Despite the lack of typical clinical manifestations of WAS, low expression of WASP could be associated with the pathogenesis of a subtype of IBD patients.

Feasibility and safety of bowel cleansing using low-volume polyethylene glycol with ascorbic acid before pediatric colonoscopy: A pilot study.

BACKGROUND AND AIM: To assess the feasibility and safety of same-day regimen of low-volume polyethylene glycol solution with ascorbic acid for bowel cleansing before colonoscopy in children. METHODS: Data on children who received polyethylene glycol solution with ascorbic acid for bowel cleansing in our department were retrospectively analyzed. On the day before the procedure, patients ate a low-residue diet and received sodium picosulfate in the evening. The following day, patients took polyethylene glycol solution with ascorbic acid in the morning; the procedure was carried out in the afternoon. Dosages of sodium picosulfate and polyethylene glycol solution with ascorbic acid were adjusted based on bodyweight. Bowel cleansing efficacy was rated on a scale of 1-5 by the colonoscopist. RESULTS: Between July 2013 and November 2014, polyethylene glycol solution with ascorbic acid was used in 112 cases (96 patients; male : female 73:39; median age 10.9 years, range 4-19 years). Ninety-one cases (81%) were able to orally ingest the prescribed amount of polyethylene glycol solution with ascorbic acid. Satisfactory bowel cleansing (cleansing grade ≥3) was attained in 87% on intention-to-treat analysis and 85% on per-protocol analysis. Cleansing grade was significantly better in children who ingested polyethylene glycol solution with ascorbic acid within 60 min (P < 0.05). There were no serious adverse events. CONCLUSION: Same-day regimen of polyethylene glycol solution with ascorbic acid is effective and safe for bowel cleansing in children.

Evaluation of the G145R Mutant of the Hepatitis B Virus as a Minor Strain in Mother-to-Child Transmission.

The role of the hepatitis B virus (HBV) mutant G145R, with a single change in amino acid 145 of the surface protein, as a minor population remains unknown in mother-to-child transmission. The minor strain as well as the major strain of the G145R mutant were evaluated in three cohorts using a locked nucleic acid probe-based real-time PCR. The breakthrough cohort consisted of children who were born to HBV carrier mothers and became HBV carriers despite immnoprophylaxis (n = 25). The control cohort consisted of HBV carriers who had no history of receiving the hepatitis B vaccine, hepatitis B immunoglobulin or antiviral treatment (n = 126). The pregnant cohort comprised pregnant women with chronic HBV infection (n = 31). In the breakthrough cohort, 6 showed positive PCR results (major, 2; minor, 4). In the control cohort, 13 showed positive PCR results (major, 0; minor, 13). HBeAg-positive patients were prone to have the G145R mutant as a minor population. Deep sequencing was performed in a total of 32 children (PCR positive, n = 13; negative, n = 19). In the breakthrough cohort, the frequency of the G145R mutant ranged from 0.54% to 6.58%. In the control cohort, the frequency of the G145R mutant ranged from 0.42% to 4.1%. Of the 31 pregnant women, 4 showed positive PCR results (major, n = 0; minor, n = 4). All of the pregnant women were positive for HBeAg and showed a high viral load. Three babies born to 3 pregnant women with the G145R mutant were evaluated. After the completion of immunoprophylaxis, 2 infants became negative for HBsAg. The remaining infant became negative for HBsAg after the first dose of HB vaccine. G145R was detected in one-fourth of the children with immunoprophylaxis failure. However, the pre-existence of the G145R mutant as a minor population in pregnant women does not always cause breakthrough infection in infants.