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Background and Aim: Serum leucine‐rich alpha‐2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. Methods: Subjects under 17 years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme‐linked immunosorbent assay kits. Results: We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200 μg/mL) were significantly greater than in remission (81 μg/mL; P < 0.001) or NC (69 μg/mL; P < 0.001). Serum calprotectin concentrations in active CD (2941 ng/mL) also were significantly greater than in remission (962 ng/mL; P < 0.05) or NC (872 ng/mL; P < 0.05). Serum LRG concentrations in active UC (134 μg/mL) were significantly greater than in remission (65 μg/mL; P < 0.01) but not significantly greater than in NC (69 μg/mL); serum calprotectin concentrations in active UC (1058 ng/mL) were not significantly different from those in remission (671 ng/mL) or NC (872 ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C‐reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C‐reactive protein, or erythrocyte sedimentation rate. Conclusions: In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO‐ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO‐ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3‐ANCA) has performed better at UC diagnosis in Japanese adults than MPO‐ANCA. The present study aimed to evaluate usefulness of PR3‐ANCA for diagnosis of UC in Japanese pediatric practice. Methods: Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3‐ANCA and MPO‐ANCA were analyzed using chemiluminescence enzyme immunoassay kits. Results: Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3‐ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3‐ANCA was 0.79, significantly greater than for MPO‐ANCA (0.58; P < 0.001). Using a cut‐off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3‐ANCA showed significantly greater sensitivity (64.9%) than MPO‐ANCA (cut‐off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). Conclusions: In Japanese children and adolescents, PR3‐ANCA performed better as a serologic marker for diagnosis of UC than MPO‐ANCA. To our knowledge, this is the first report of such a comparison. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis B virus (HBV) can have mutations that include the a determinant, which causes breakthrough infection. In particular, a single mutation at amino acid 145 of the surface protein (G145) is frequently reported in the failure of prophylactic treatment. The aim of this study was to evaluate the frequency of the a determinant mutants, especially the G145 variant, in Japan, where universal vaccination has not been adopted. Methods The present study was a retrospective study. The study cohorts were defined as follows: group 1, children with failure to prevent mother-to-child transmission despite immunoprophylaxis (n = 18, male/female = 8/10, age 1-14 years; median 6 years); group 2, HBV carriers who had not received vaccination or hepatitis B immunoglobulin (n = 107, male/female = 107, age 1-52 years; median 16 years). To detect the G145R and G145A mutants in patients, we designed 3 probes for real-time PCR. We also performed direct sequencing and cloning of PCR products. Results By mutant-specific real-time PCR, one subject (5.6%) was positive for the G145R mutant in group 1, while the G145 mutant was undetectable in group 2. The a determinant mutants were detected in one (5.6%) of the group 1 subjects and 10 (9.3%) of the group 2 subjects using direct sequencing, but direct sequencing did not reveal the G145 mutant as a predominant strain in the two groups. However, the subject who was positive according to the mutant-specific real-time PCR in group 1 had overlapped peaks at nt 587 in the electropherogram. In group 2, 11 patients had overlapped peaks at nt 587 in the electropherogram. Cloning of PCR products allowed detection of the G145R mutant as a minor strain in 7 (group 1: 1 subject, group 2: 6 subjects) of 12 subjects who had overlapped peaks at nt 587 in the electropherogram. Conclusions The frequency of the a determinant mutants was not high in Japan. However, the G145R mutant was often present as a minor population in children and adults. HBV carriers might have the a determinant mutants as a minor form.

Abstract Background The administration of hepatitis B immunoglobulin followed by hepatitis B vaccine can result in a protective efficacy of almost 90% in mother-to-child transmission of hepatitis B virus (HBV). However, little is known about immunity against HBV infection in children after immunoprophylactic treatment. We tried to assess the association between T-cell responses and viremia in children after successful prophylactic treatment. Methods Thirteen children and their 8 HBV carrier mothers (8 families), who were positive for human leukocyte antigen (HLA)-A24, were enrolled in this study. All of the 13 children received immunoprophylactic treatment and became negative for hepatitis B surface antigen (HBsAg) after birth. HBV-specific cytotoxic T lymphocyte (CTL) responses were evaluated using IFNγ - enzyme-linked immunosorbent spot (ELISPOT) and major histocompatibility complex class I peptide pentamer assays. Serum HBV DNA was measured by real-time PCR. Results Significant HBV-specific T-cell responses were detected in 2 (15%) of the 13 children by ELISPOT. However, the frequency of HLA-A24-HBV-specific CTLs was very low in both HBV carrier mothers and children using pentamers. Of the 13 children, 4 (31%) were positive for serum HBV DNA. However, the levels of serum HBV DNA were 100 copies/ml or less. One of the 2 children in whom significant HBV-specific CTL responses were detectable was positive for serum HBV DNA. Conclusions HBV core and polymerase-specific T-cell responses were detected and a low-dose viremia was observed in children after successful immunoprophylaxis treatment. Although the presence of viremia was not related to HBV-specific T-cell responses, CTLs might play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment.

Abstract Background Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. Methods One thousand and thirty-six people (Male/Female = 594/442, Age: 0–19 yr.; 959 subjects, 20–29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60–92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. Results We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. Conclusion CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to determine the characteristics of children with autoimmune hepatitis (AIH) in Japan. Methods: Questionnaires that asked about patients newly diagnosed with AIH from 2009 to 2013 were sent to hospitals certified as training facilities for pediatrics in January 2015. Results: A total of 35 patients were enrolled. The median age at diagnosis was 10 years (range, 3 months–15 years), and the male‐to‐female ratio was 2:3. Female patients were more prevalent among those older than 10 years and male patients were more prevalent in those younger than 10 years. Fifteen patients had jaundice as a subjective symptom, and 5 had hepatic coma grade II. Liver histology classified 20 as chronic hepatitis, 8 as acute hepatitis, and 4 as cirrhosis. Liver histology was not described in 4 patients. Among the 35 patients, 32 were treated with corticosteroids and 29 were initially treated with methylprednisolone pulse therapy. Corticosteroid therapy was effective in 27 patients and ineffective in 1 patient. Plasma exchange with continuous i.v. infusion of cyclosporine A was given to 7 patients with acute hepatitis. Of these, 4 patients presented with fulminant hepatitis and received high‐flow, continuous hemodiafiltration. Conclusions: This survey clarified that the clinical profile of pediatric AIH in Japan is not only different from that of adult AIH in Japan but is also different from that of pediatric AIH in other countries. [ABSTRACT FROM AUTHOR]

Objectives. To determine the prevalence and effect of dietary habits on functional constipation in preschool and early elementary school children in Japan. Study Design. A total of 3595 children aged 3 to 8 years from 28 nursery schools and 22 elementary schools in Yokohama City, Kanagawa Prefecture, Japan, were evaluated. The subjects were divided into a functional constipation group and a nonfunctional constipation group according to the Rome III criteria. Dietary intake data were collected using a brief-type, self-administered, diet-history questionnaire validated for Japanese preschool-aged children. Results. Of the 3595 subjects evaluated, 718 (20.0%) had functional constipation. The association between functional constipation and gender was not statistically significant (p=0.617). A decrease in bowel frequency was observed in 15.9% of those with functional constipation. There was no significant difference in the proportion of participants in the constipation group by age (p=0.112). Binomial logistic regression analysis indicated that only fat per 100 kcal positively correlated with functional constipation [odds ratio = 1.216, 95% confidence interval: 1.0476–1.412]. Conclusions. Functional constipation is common among children in preschool and early elementary school in urban areas of Japan. Parents should pay attention to constipation-related symptoms other than defecation frequency. A high-fat diet should be avoided to prevent functional constipation. [ABSTRACT FROM AUTHOR]

Background The aim of the present study was to clarify the roles of cytomegalovirus ( CMV), Epstein-Barr virus ( EBV), and human herpesvirus 6 ( HHV-6) in immunocompetent children with acute liver dysfunction not resulting from hepatitis virus. Methods Sixty-eight children (median age, 3 years) hospitalized as a result of acute liver dysfunction were enrolled in this study. Hepatitis A, B, and C were excluded. The prevalence of CMV, EBV, and HHV-6 and viral DNA load in whole blood was prospectively evaluated on multiplex real-time polymerase chain reaction ( PCR). Results Of the 68 children with acute liver dysfunction, multiplex real-time PCR was positive in 30 (44%). CMV, EBV, and HHV-6 DNA were detected in 13 (19%), 14 (21%), and seven (10%), respectively. Serum CMV immunoglobulin (Ig)G/IgM and EBV viral capsid antigen IgG/IgM were measured in 40 ( CMV DNA positive, n = 10; negative, n = 30) and 45 ( EBV DNA positive, n = 14; negative, n = 31) of the 68 children, respectively. Eighteen percent ( CMV, 7/40) and 9% ( EBV, 4/45) were positive for both PCR and viral-specific IgM. There was no significant difference in CMV and EBV viral load between IgM-positive and -negative children with viremia. Conclusions CMV, EBV, and HHV-6 DNA were frequently detected in immunocompetent children with acute liver dysfunction, but primary CMV and EBV infection were confirmed in 10-20% of the children with acute liver dysfunction. The combination of PCR assay and serology is necessary to make a diagnosis of acute liver dysfunction due to primary CMV, EBV and/or HHV-6 infection in immunocompetent children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It is not known that saliva is useful to diagnose Mycoplasma pneumoniae ( M. pneumoniae) infection by PCR. We evaluated prospectively whether crude saliva samples without the DNA extraction process were useful for the detection of M. pneumoniae DNA in a locked nucleic acid (LNA) probe-based real-time PCR assay. Fifty-one clinical specimens (29 sputum, 22 saliva) that were positive by conventional M. pneumoniae-specific PCR were evaluated in this study. We designed an LNA probe-based real-time PCR that could discriminate the mutant strain (A2063G mutation) from the wild-type strain. All the 51 samples treated with DNA extraction were positive using the LNA probe-based real-time PCR. The results of the real-time PCR with DNA extraction were consistent with the sequence analysis. Of the 51 samples without DNA extraction, on the other hand, 41 (80.4 %) were positive by real-time PCR. Of 29 sputum samples without DNA extraction, 23 (79.3 %) were positive by real-time PCR; of the 22 saliva samples without DNA extraction, 18 (81.8 %) were positive by real-time PCR. There was a statistically significant difference in the amplified DNA levels with extraction between the direct real-time PCR-positive samples (mean ± SD, 7.5 ± 1.6 log copies/ml) and PCR-negative samples (4.2 ± 0.8 log copies/ml) ( P < 0.001). Saliva was useful for a template for PCR as well as sputum. In addition, crude samples were useful for real-time PCR when the samples had medium or high DNA levels. However, samples with low DNA levels sometimes showed false-negative results in direct real-time PCR. [ABSTRACT FROM AUTHOR]

Background: The administration of hepatitis B immunoglobulin followed by hepatitis B vaccine can result in a protective efficacy of almost 90% in mother-to-child transmission of hepatitis B virus (HBV). However, little is known about immunity against HBV infection in children after immunoprophylactic treatment. We tried to assess the association between T-cell responses and viremia in children after successful prophylactic treatment. Methods: Thirteen children and their 8 HBV carrier mothers (8 families), who were positive for human leukocyte antigen (HLA)-A24, were enrolled in this study. All of the 13 children received immunoprophylactic treatment and became negative for hepatitis B surface antigen (HBsAg) after birth. HBV-specific cytotoxic T lymphocyte (CTL) responses were evaluated using IFNγ - enzyme-linked immunosorbent spot (ELISPOT) and major histocompatibility complex class I peptide pentamer assays. Serum HBV DNA was measured by real-time PCR. Results: Significant HBV-specific T-cell responses were detected in 2 (15%) of the 13 children by ELISPOT. However, the frequency of HLA-A24-HBV-specific CTLs was very low in both HBV carrier mothers and children using pentamers. Of the 13 children, 4 (31%) were positive for serum HBV DNA. However, the levels of serum HBV DNA were 100 copies/ml or less. One of the 2 children in whom significant HBV-specific CTL responses were detectable was positive for serum HBV DNA. Conclusions: HBV core and polymerase-specific T-cell responses were detected and a low-dose viremia was observed in children after successful immunoprophylaxis treatment. Although the presence of viremia was not related to HBVspecific T-cell responses, CTLs might play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To estimate an efficacy of intravenous methylprednisolone pulse therapy (m-PSL) and the occurrence of corticosteroid-related side effects in children with autoimmune hepatitis (AIH), compared with oral corticosteroid therapy. Study design: The subjects consisted of nine children with AIH. Patients were divided into two groups. Group 1 was consisted of four patients who were treated with conventional oral prednisone therapy without m-PSL. Group 2 was consisted of five children who were treated with m-PSL as an induction therapy and maintained on oral prednisone. Results: The median duration needed for normalization of alanine aminotransferase was 285 days (range 18–617 days) in group 1 and 54 days (range 15–116 days) in group 2. The most frequent side effects were obesity and growth retardation. The Z-score in group 1 tended to be lower than in group 2 and body mass index in group 1 tended to be higher than in group 2. Conclusion: The m-PSL may become a safe and effective therapy for children with AIH. Further study is needed to establish the appropriate therapy for AIH in children. [Copyright &y& Elsevier]

Background: Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. Methods: One thousand and thirty-six people (Male/Female = 594/442, Age: 0-19 yr.; 959 subjects, 20-29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60-92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. Results: We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. Conclusion: CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group. [ABSTRACT FROM AUTHOR]

The aim of our study was to identify the histologic features in children with chronic hepatitis C including bile duct damage, lymphoid follicles and/or aggregates in portal tracts, fat droplets, and Mallory body-like material in hepatocytes. We examined 54 liver biopsies from 49 children with chronic hepatitis C and 25 specimens from children with chronic hepatitis B. Histologic diagnoses were based on the new classification of chronic hepatitis. Necroinflammation, fibrosis, lymphoid follicles and/or aggregates, bile duct damage, fat droplets, Mallory body-like material, and iron deposit were scored. The necroinflammation and fibrosis scores were higher in chronic hepatitis B than in chronic hepatitis C (p < .05 ). In chronic hepatitis C, lymphoid follicles and/or aggregates, fatty droplets, and iron deposition were more commonly observed in children with histories of hematologic disorders who received massive doses of cytotoxic and immunosuppressive agents than in those with good prognosis. The liver histology of children with chronic hepatitis C does not have specific features that allow differentiation of chronic hepatitis C from chronic hepatitis B, which is a more aggressive disease. [ABSTRACT FROM AUTHOR]