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Background and Aims: We evaluated the effectiveness and safety of pan‐genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct‐acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)‐infected adolescents (12–18 years), older children (6–11 years), and young children (3–5 years). The purpose of this systematic review and meta‐analysis was to inform the World Health Organization (WHO) guidelines. Methods: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV‐infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS‐I tool. Data were pooled using random‐effects models, and certainty of the evidence was assessed using the GRADE approach. Results: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96–100), 96% (90–100), and 96% (83–100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90–99), 93% (86–98), and 83% (70–93), for SOF/VEL, respectively; and 100% (97–100) and 100% (94–100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). Conclusions: All three pan‐genotypic DAA regimens were highly effective and well‐tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single‐arm non‐randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co‐infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO Record: CRD42020146752. [ABSTRACT FROM AUTHOR]

Summary: Background: The effect of direct‐acting anti‐virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. Aim: To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. Methods: We performed a systematic review and meta‐analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post‐treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post‐treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman‐Tukey double arcsine transformation. Random effects model was used for all analyses. Results: Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post‐treatment week 12 was 100% (95% confidence interval: 100‐100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Conclusions: Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults. [ABSTRACT FROM AUTHOR]

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18‐year‐olds with HCV infection in specialist follow up in a 12‐month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross‐sectional, web‐based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three‐quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV‐related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment‐naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct‐acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6‐10 and 42% in those 3‐5 years of age (Pearson correlation coefficient −0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow‐up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct‐acting antivirals in these children. [ABSTRACT FROM AUTHOR]

See Article on Page 319 [ABSTRACT FROM AUTHOR]

A retrospective multicentre study conducted in Italy analyzed hospitalization trends for bronchiolitis in infants between October 2019 and March 2023. The study found that bronchiolitis cases, particularly those caused by the respiratory syncytial virus (RSV), experienced a significant reduction during the 2020-2021 winter due to preventive measures implemented during the COVID-19 pandemic. However, subsequent winters saw a notable and sustained increase in bronchiolitis hospitalizations, with the 2022-2023 winter period experiencing a 47% higher rate compared to the pre-pandemic winter of 2019-2020. The changing seasonality of bronchiolitis, including altered patterns of RSV circulation, poses challenges for disease control strategies and immunoprophylaxis measures. Further research is needed to monitor the epidemiology of bronchiolitis and inform public health interventions. [Extracted from the article]

LINKED CONTENT: This article is linked to Indolfi et al and Garrido & Macedo papers. To view these articles, visit https://doi.org/10.1111/apt.16037 and https://doi.org/10.1111/apt.16546 [ABSTRACT FROM AUTHOR]

Indolfi G, Heaton N, Smith M, Mieli-Vergani G, Zuckerman M. Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation. Clin Transplant 2012: 26: E55-E61. © 2011 John Wiley & Sons A/S. Abstract: Background: The clinical impact of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections in the early post-transplantation period are poorly documented. We investigated the prevalence and timing of EBV and CMV infections during the first 21 d post-transplantation in relation to graft function and acute cellular rejection in a large cohort of pediatric liver transplantation recipients. Patients and methods: Clinical, biochemical, virological, and histopathological data of 62 consecutive children who received a liver transplant were reviewed retrospectively. Results: Seventeen patients (27%) developed EBV and 11 (18%) CMV viremia (mean interval from surgery: 7.6 d, SD 3.6 and 8.7 d, SD 6.4, respectively). EBV and CMV viremia were more common as a consequence of reactivation than of primary infection. EBV viremic recipients had more often abnormal bilirubin levels [p = 0.01; OR 5.8: 95% CI 1.3-25.5]. Acute rejection was diagnosed in 20 recipients (32.3%). No correlation was found between rejection and EBV and CMV serology before transplantation and viremia after transplantation (mean interval between the diagnosis of rejection and the detection of EBV DNA and CMV DNA: one d, SD 4.4 and five d, SD 9.2, respectively). Conclusion: EBV and CMV viremia occur at a very early-stage post-transplantation and do not appear to affect the short-term outcome of the transplant. [ABSTRACT FROM AUTHOR]

Objective The reported data on thyroid function and anti-thyroid autoantibodies in adults with untreated hepatitis C virus (HCV) infection are controversial. Data are scarce for HCV-infected children, and only in those treated with interferon-α (IFN-α). We investigated thyroid function and anti-thyroid autoantibodies in a cohort of untreated children with vertically acquired, chronic, HCV infection. Design and patients FT4 and TSH serum levels (measured by immunometric assays) and anti-thyroglobulin (TgA) and anti-thyroperoxidase (TPOA) antibodies (evaluated by fluorescence enzymatic immunoassays) were studied in 36 consecutive HCV-infected children and 150 age- and sex-matched controls. The prevalence of thyroid involvement was also related to family history of autoimmune disease, distribution of HCV genotypes, and duration and activity of HCV infection. Results Four out of 36 (11·1%) HCV-infected children and 4/150 controls (2·7%) showed subclinical hypothyroidism [ P = 0·04; relative risk (RR) 4·56, 95% confidence interval (CI) 1·08–19·21]. None of these had anti-thyroid autoantibodies. Two out of 36 (5·6%) HCV-infected children and 1/150 (0·7%) controls had increased TgA values with normal levels of TSH ( P > 0·05). Subclinical hypothyroidism and anti-thyroid autoantibodies were not related to family history of autoimmune disease, duration of infection, HCV viral load, liver function or different HCV genotype distribution, but seemed to be related to the presence of active HCV infection. Conclusions Our data suggest a role for HCV infection in the development of nonautoimmune thyroid disease in untreated HCV-infected children, confirming previous studies in adults. Clinicians should be aware of thyroid dysfunction even in untreated children. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health‐related quality of life (HRQL) of children with chronic hepatitis C. Methods: In the non‐commercial, non‐randomized, open‐label PANDAA‐PED study, 50 children aged 6–18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN‐27 questionnaires, which included 5 dimensions of HRQL, for child self‐reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child–parent agreement was analysed using the intra‐class correlation coefficient (ICC) and Bland–Altman test. Results: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well‐being based on the children's self‐assessment (from 48.53 to 51.21, p =.03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p =.06) was noticed. After the treatment, the proportion of children self‐assessing their physical well‐being as below normal significantly decreased from 17% to 5% (p =.007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self‐reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland–Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). Conclusions: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well‐being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future. [ABSTRACT FROM AUTHOR]

Aim: The aim of this narrative review was to provide a comprehensive summary of the characteristics of gastrointestinal (GI) involvement in the most common paediatric primary vasculitides.Methods: We used PubMed to primarily identify papers, reviews, case series and editorials published in English from 2000 until 31 January 2020. Based on this, we report the prevalence, clinical manifestations, diagnostic approaches and management of GI involvement in each vasculitis.Results: Vasculitides are inflammatory blood vessel diseases, and the majority can affect the GI system with vascular, GI tract or solid organ involvement. GI involvement can sometimes complicate and delay the correct diagnosis. Clinical findings are usually nonspecific symptoms, such as fever, abdominal pain, nausea, vomiting and diarrhoea. Bleeding should alert paediatricians to the possibility of severe complicated vasculitis. Diagnosis relies mostly on imaging. If it goes unrecognised, GI involvement in paediatric vasculitis is a serious cause of morbidity and even mortality, related to bowel ischaemia and perforation. Treatment of GI symptoms depends on the type of vasculitis and usually involves high-dose steroids and immunosuppressants.Conclusion: GI manifestations in the most common paediatric primary vasculitides were usually nonspecific, diagnosis mostly relied on imaging, and treatment usually involved high-dose corticosteroids and immunosuppressants. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of this non‐commercial, open‐label, real‐life, non‐randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection. Methods: Fifty patients qualified for the 12‐week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real‐time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). Results: Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty‐seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty‐three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008). Conclusions: Results of the PANDAA‐PED study indicated a 100% effectiveness of a 12‐week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 3-year-old girl with bleeding and diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHS) and coeliac disease (CD). Physical examination was normal which showed only diffuse multiple subcutaneous haematomas. The article discusses LAHS characterized by the presence of low prothrombin activity (PA). Clinicians should keep in mind that LA is associated with bleeding and the possibility of association between CD and LA which is rare in children.

A letter to the editor is presented commenting on the etiology of immune (idiopathic) thrombocytopenic purpura (ITP) and portal vein thrombosis in children.

The article provides information on the skin disease called podoconiosis. The disease is the result of progressive obliterating endolymphangitism, induced by the absorption of ultrafine silica particles through the skin of the feet, especially when a person is exposed to red clay soil. The early signs of the said disease are recurrent episodes of burning and edema of one foot. It is noted in the article that established lymphedema can progress to severe elephantiasis.

Bartonella henselae is an unusual and rarely suspected osteomyelitis etiologic agent. We present a case of low back‐pain in a 10‐year‐old female which lead to a challenging diagnostic work‐up due to subtle imaging findings. The diagnosis was Bartonella henselae vertebral osteomyelitis mimicking bone tumor. Bartonella infection should be included in the differential diagnosis of pediatric back pain associated with fever, especially if there is a history of exposure to cats. MRI is the most sensitive radiographic technique to define bone lesions, but in case of non‐specific findings, the biopsy of the lesion is mandatory. [ABSTRACT FROM AUTHOR]

Background: Cerebrotendinous xanthomatosis (CTX) is a disorder of bile acid (BA) metabolism due to biallelic mutations in CYP27A1. The deposition of cholesterol and cholestanol in multiple tissues results, manifesting as neurologic disease in adults or older children. Neonatal cholestasis (NC) as a presentation of CTX is rare; it may self‐resolve or persist, evolving to require liver transplantation (LT). Methods: We present in the context of similar reports an instance of CTX manifest as NC and requiring LT. Results: A girl aged 4mo was evaluated for NC with normal serum gamma‐glutamyl transpeptidase activity. An extensive diagnostic work‐up, including liver biopsy, identified no etiology. Rapid progression to end‐stage liver disease required LT aged 5mo. The explanted liver showed hepatocyte loss and micronodular cirrhosis. Bile salt export pump (BSEP), encoded by ABCB11, was not demonstrable immunohistochemically. Both severe ABCB11 disease and NR1H4 disease—NR1H4 encodes farsenoid‐X receptor, necessary for ABCB11 transcription—were considered. However, selected liver disorder panel sequencing and mass‐spectrometry urinary BA profiling identified CTX, with homozygosity for the predictedly pathogenic CYP27A1 variant c.646G > C p.(Ala216Pro). Variation in other genes associated with intrahepatic cholestasis was not detected. Immunohistochemical study of the liver‐biopsy specimen found marked deficiency of CYP27A1 expression; BSEP expression was unremarkable. Aged 2y, the girl is free from neurologic disease. Conclusions: Bile acid synthesis disorders should be routinely included in the NC/"neonatal hepatitis" work‐up. The mutually supportive triple approach of BA profiling, immunohistochemical study, and genetic analysis may optimally address diagnosis in CTX, a treatable disease with widely varying presentation. [ABSTRACT FROM AUTHOR]

The aims of this prospective study were as follows: (1) to describe the natural history of chronic hepatitis B virus (HBV) infection in a large cohort of untreated children followed at a single centre and (2) to evaluate whether or not the new European Association for the Study of Liver (EASL) classification for the phases of HBV infection in adults can be used for children. All children who presented at the Liver Unit of our hospital from 1 January 1987 to 31 December 2019 and were diagnosed with chronic HBV infection were enrolled. The final sample consisted of 152 children. The median duration of the follow‐up was 83 months (range 7‐232). At baseline, 125 patients (82.2%) were HBeAg positive (85.3% abnormal alanine aminotransferase (ALT) levels), and 24 (15.8%) were HBeAg‐negative (93.3% abnormal ALT). At the end of the observation period, 62 of the HBeAg‐positive patients (40.7%) achieved HBeAg seroconversion (median age 9.45 years, range 0.8‐19) and 2 (1.4%) achieved HBsAg seroconversion. Elevated ALT serum levels at baseline (P =.011), lower baseline HBV DNA levels (P <.001) and Asian ethnicity (P =.0001) were identified as predisposing factors towards HBeAg seroconversion. EASL criteria could not be applied to 43.3% and 43.5% of the children at baseline and at end of observation, respectively, that were grouped into an undetermined phenotype category. According to the results of the present study, the new EASL guidelines for adults with HBV infection cannot be applied in a satisfactory manner in children. [ABSTRACT FROM AUTHOR]

We describe a case of bilateral parenchymal consolidation with sudden respiratory distress in a preterm baby as a complication of peripherally inserted central catheter (PICC) dislocation. The X-rays showed bilateral pulmonary consolidation with the catheter tip initially located in the right, and later in the left pulmonary artery. The catheter was withdrawn. As soon as the catheter was repositioned all clinical signs and symptoms disappeared. Neonatologists should consider the possibility of dramatic respiratory distress deriving from PICC dislocation. Careful tip catheter placement and conscientious monitoring may reduce morbidity. [ABSTRACT FROM AUTHOR]

Summary: Russia has one of the highest prevalences of paediatric chronic hepatitis C infection (CHC). Our aim was to provide a detailed characterization of children and adolescents with CHC including treatment outcomes. Thus, an observational study of children with CHC aged <18 years was conducted in three hepatology centres from November 2014 to May 2017. Of 301 children (52% male), 196 (65%) acquired HCV vertically, 70 (23%) had a history of blood transfusion or invasive procedures, 1 injecting drug use and 34 (11%) had no known risk factors. Median age at HCV diagnosis was 3.1 [interquartile range, IQR 1.1, 8.2] and 10.8 [7.4, 14.7] at last follow‐up. The most common genotype was 1b (51%), followed by 3 (37%). Over a quarter of patients (84, 28%) had raised liver transaminases. Of 92 with liver biopsy, 38 (41%) had bridging fibrosis (median age 10.4 [7.1, 14.1]). Of 223 evaluated by transient elastography, 67 (30%) had liver stiffness ≥5.0 kPa. For each year, increase in age mean stiffness increased by 0.09 kPa (95% CI 0.05, 0.13, P < 0.001). There was significant correlation between liver stiffness and biopsy results (Tau‐b = 0.29, P = 0.042). Of 205 treated with IFN‐based regimens, 100 (49%) had SVR24. Most children (191, 93%) experienced adverse reactions, leading to treatment discontinuation in 6 (3%). In conclusion, a third of children acquired HCV via nonvertical routes and a substantial proportion of those with liver biopsy had advanced liver disease. Only half of children achieved SVR24 with IFN‐based regimens highlighting the need for more effective and better‐tolerated treatments with direct‐acting antivirals. Further studies are warranted in Russia on causes and prevention of nonvertical transmission of HCV in children. [ABSTRACT FROM AUTHOR]