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HBV and HCV are the predominant causes of chronic viral hepatitis in children and adults. The main purposes of the present review are to provide the reader with a comprehensive overview of the currently available therapies for chronic hepatitis B and C in children and to critically review the current guidelines and indications for treatment provided by the major international societies and by the consensus of expert panels. Overall, a conservative approach is generally warranted in children with chronic hepatitis B. For HCV, the high effectiveness of pegylated interferon and ribavirin in children with genotype 2 or 3 chronic infection supports the decision to treat. For genotype 1 infection the encouraging results of the use of direct antiviral agents in adults suggest a more conservative approach.

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.

Background and aim: Treatment of chronic hepatitis C in children is controversial and its role in the clinical practice is unknown. We retrospectively investigated the impact of treatment in a large cohort of children with chronic hepatitis C over the past 20years. Methods: 376 hepatitis C virus RNApositive children were recruited consecutively in five Italian centres since 1990and followed for1–17years. Results: 86 (23%)subjects were treated: 73 with recombinant interferon alone and 13 with pegylated-interferon and ribavirin. Sustained clearance of hepatitis C virus RNA was observed in 25%of the former, in 92%of the latter and in 9% of untreated cases(p < 0.001). Loss of viraemia was recorded in all children with genotype2–3 and in 6of7 with hepatitis C virus genotype 1 treated with combination therapy.At last evaluation 45% of patients were young adults and 15%had cleared viraemia. Overall, 152 (40%)were putative candidates to therapy. Conclusions: Few Italian children with chronic hepatitis C have been treated in the past 20years.The poor propensity to spontaneous clearance of viraemia and the efficacy of ombination therapy should encourage to consider treatment in attempt to shorten the duration of viral replication.

Summary 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.

Summary. SEN is a newly discovered blood-transmissible virus. Among its variants, SENV-D and -H are most often associated with non-A, -E hepatitis. Very little is known about the risk of vertical transmission of the virus. By using polymerase chain reaction with specific primers for SENV-D and -H, we investigated the prevalence of SENV-H and -D infection, the transmission rate of SENV infection and clinical features of SENV-infected children in 89 hepatitis C virus (HCV)-positive human immunodeficiency virus type 1-negative mothers. SENV infection was found in 36 (40%) mothers, and SENV-D was more frequent than SENV-H infection (34/36, 94%vs 5/36, 14%, P

Maternal injection drug use and peripheral blood mononuclear cell infection by hepatitis C virus are important risk factors for perinatal transmission of the virus. The aim of present study was to evaluate the independent association of these two factors on perinatal transmission. Forty-eight consecutive mothers who transmitted infection to their offspring and 122 consecutive mothers who did not, together with their children, were examined. Both maternal injection drug use and peripheral blood mononuclear cell infection were significantly more frequent in infected than in uninfected children (respectively P = 0.04; odds ratio 2.33, 95% confidence intervals 1.02–5.42 and P

Summary Background Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity. Aim To evaluate NK cells in children according to the different outcomes of the infection. Methods In this cross-sectional study, we examined numbers and phenotypes of circulating NK cells from a homogenous cohort of Italian children with vertically acquired hepatitis C. Results We compared 31 children who developed chronic infection with nine who presented spontaneous clearance and 13 controls. CD56+CD3− NK cell numbers were consistently lower in the persistently infected group (P = 0.03 and 0.04). This decrease was due to depletions of CD56dim NK cells (P = 0.03 chronic infection vs. spontaneous clearance), while CD56bright NK cells were expanded (P = 0.03). No significant difference was found in the frequencies of CD56+CD16+ and CD56dimCD16− cells. Perforin expression was higher in children with chronic infection (P = 0.03 vs. spontaneous clearance). Conclusions Altered NK cells number and phenotypes could impact the outcome of HCV infection in children following vertical transmission. This study suggests for the first time that NK cells cytolytic function, featured by CD56dim cells, contributes to the elimination of HCV in children presenting spontaneous clearance.

Objectives The objective of this systematic review was to summarize evidence regarding hepatitis C in hepatitis C virus/human immunodeficiency virus (HCV/HIV)-co-infected children focusing on mother-to-child transmission, clinical and laboratory features, outcome, and therapies. Methods A literature search was performed using multiple keywords and standardized terminology in MEDLINE, EMBASE, and Cochrane databases dating back to their inception up to April 1, 2015, using the following terms hepatitis C virus, HIV, and child. Results Fifty-five of 367 publications were selected for inclusion. In co-infected children, HIV impacted all the different aspects of HCV infection. Maternal HIV infection increased the risk of vertical transmission of hepatitis C. Children with HCV/HIV co-infection presented a lower rate of spontaneous clearance of HCV, were more commonly HCV viraemic, and had higher values of alanine aminotransferase when compared with HCV-monoinfected children. No relevant difference was reported between monoinfection and co-infection with regard to clinical findings. Although the data on the outcome of hepatitis C in the context of co-infection were limited, they were highly suggestive of a more severe outcome in terms of fibrosis in co-infected children. No pediatric data were available on the role of antiretroviral therapy as a cofactor of liver injury in HCV/HIV co-infection. The efficacy of pegylated interferon-α and ribavirin in children with HCV/HIV co-infection was lower than in monoinfected children. Conclusions The effect of HIV co-infection on HCV-related disease was clear with most studies indicating that HIV accelerates HCV progression and reduces the efficacy of the available anti-HCV therapies.

We report the first human case of meningitis and sepsis caused in a child by Actinobacillus suis or A. equuli , a common opportunistic pathogen of swine or horses, respectively. Identification was performed by matrix-assisted laser desorption ionization–time of flight mass spectrometry and real-time PCR assay. A previous visit to a farm was suspected as the source of infection.

Chronic hepatitis C in children is usually considered a clinically mild and slowly progressive disease. Few pediatric studies focused on histopathology of children with hepatitis C are available. Those available show, overall, a wide spectrum of findings ranging from normal liver to cirrhosis and hepatocellular carcinoma. The present systematic review provides a comprehensive overview of the studies that explored histopathology in children with hepatitis C. Factors affecting the presence and the degree of necroinflammation, fibrosis and steatosis and the risk of progression to advanced liver disease were extensively evaluated. Insights on the possible role of histopathology findings in the decision-making process of whether or not to treat children with hepatitis C are provided.

Background: Paediatric acute hematogenous osteomyelitis (AHOM) is a serious disease requiring early diagnosis and treatment. To review the clinical presentation, management and organisms responsible for AHOM, and to explore risk factors for complicated AHOM, a large cohort referring to a single center over a 6-year period was evaluated. Methods: Data from children with AHOM, hospitalized between 2010 and 2015, and aged > 1 month, were retrospectively collected and analyzed. Results: 121 children (median age 4.8 years; 55.4% males) were included. Fever at onset was present in 55/121 children (45.5%); the lower limb was most frequently affected (n = 68/121; 56.2%). Microbiological diagnosis (by culture and/or polymerase chain reaction (PCR)) was reached in 33.3% cases. Blood and pus/biopsy culture sensitivities were 32.4% and 46.4%, respectively. PCR sensitivity was 3.6% (2/55) on blood, and 66.6% (16/24) on pus/biopsy sample. Staphylococcus aureus was the most commonly identified pathogen (n = 20); no methicillin-resistant Staphylococcus aureus (MRSA) was isolated, 10.0% (n = 2) strains were Panton-Valentine-Leukocidin (PVL) producer; 48.8% (59/121) cases were complicated. At univariate analysis, factors associated with complicated AHOM were: recent fever episode, fever at onset, upper limb involvement, white blood count (WBC) ≥ 12,000/µL, C reactive protein (CRP) ≥ 10 mg/L, S. aureus infection. At multivariate analyses S. aureus infection remained the only risk factor for complicated AHOM (aOR = 3.388 (95%CI: 1.061–10.824); p-value = 0.039). Conclusions: In this study microbiological diagnosis was obtained in over one third of cases. Empiric treatment targeting methicillin-sensitive Staphylococcus aureus seems to be justified by available microbiological data.

The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3–5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children.

Objective Recent genome-wide association studies performed in adults correlated single-nucleotide polymorphisms (SNPs rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin 28B gene, with spontaneous clearance of hepatitis C virus and with response to treatment with paginated interferon and ribavirin. The aim of the present collaborative study was to evaluate the rs12979860 SNP in a large cohort of Italian children with perinatal acquisition of hepatitis C. Methods Children were prospectively enrolled in 2 Italian centers. The interleukin 28B rs12979860 SNP was studied according to the diagnosis of chronic infection or spontaneous clearance. Results One hundred thirty children (86.7%) with chronic infection and 23 (13.3%) with spontaneous clearance of the virus were enrolled. Overall, the interleukin 28B C/C and C/T-T/T genotypes were found in 57 (37.3%) and 96 (62.7%) children, respectively. The proportion of C/C genotype was higher among children who cleared infection (14/23; 60.9%) compared with children with chronic infection (43/130; 33.1%; P = 0.01; odds ratio 3.15; 90% confidence intervals 1.34-7.53). Conclusions The present study showed that, as already demonstrated in adults, children with the rs12979860 C/C SNP of the interleukin 28B gene have a higher probability of spontaneous clearance of hepatitis C virus.

The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.

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.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations. Eleven were novel, while twenty one already described mutations were identified in new populations in this study. In particular, mutation analysis of 13 families of Romanian origin showed a high prevalence of the p.H1069Q mutation (50%). Detection of new mutations in the ATP7B gene in new populations increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring.

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.Clinical, biochemical, virological, and histopathological data of 62 consecutive children who received a liver transplant were reviewed retrospectively.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).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.

In industrialized countries, hepatitis C virus (HCV) is the most common cause of chronic liver disease in children. Perinatal transmission is the leading cause of infection. Perinatal transmission is confined almost always to women with detectable HCV ribonucleic acid (RNA) in the peripheral blood by the polymerase chain reaction but all children born to women with anti-HCV antibodies should be tested for HCV. Some but not all studies found that a high concentration of serum HCV RNA is associated with a higher risk of transmission. Maternal peripheral blood mononuclear cell infection by HCV, membrane rupture of longer than 6 hr before delivery, and procedures exposing the infant to maternal blood infected with HCV during vaginal delivery are associated with an increased risk of transmission. Maternal coinfection with HCV and human immunodeficiency virus, maternal history of intravenous drug use and of HCV infection of the sexual partner of the mother predict the risk of perinatal transmission and are dependent on the peripheral blood mononuclear cell infection by HCV. Delivery by Cesarean section is not recommended in pregnant women infected with HCV. Infected mothers can breast feed safely their infants if the nipples are not damaged. A previous delivery of a child infected perinatally with HCV does not increase the risk of transmission in subsequent pregnancies. Immunogenetic factors and HCV genotypes are not related to HCV perinatal transmission. Despite an increased understanding of the risk factors involved in perinatal transmission of HCV, to date little is known about the transmission mechanisms and timing.

The aims of this study were to identify demographic, clinical and laboratory characteristics associated with reactive thrombocytosis useful for clinical management and to evaluate potential complications of this condition in a cohort of children selected for they young age as at high risk of reactive thrombocytosis. Retrospective analysis of medical records of 239 children among 902 aged 1-24 months, hospitalized during a 12-month period, and discharged with a diagnosis of infectious disease was performed. One hundred and nineteen children out of 239 (49.8%) presented thrombocytosis (>500 platelets x 10(9)/L; normal range 150-499 x 10(9)/L), 81/119 (68%) on admission. The incidences of thrombocytosis or extreme thrombocytosis (>1,000 x 10(9)/L) were 13.2% (119/902) and 0.8% (7/902). Thrombocytotic children had higher counts of white blood cells and had been treated more frequently with steroids (36/82, 43.9% vs. 5/53, 9.4%; p = 5 x 10(-5); relative risk 7.51, 95% confidence intervals 2.71-20.82). No significant difference was found in relation to sex, age, fever, C reactive protein level, diagnoses and antibiotic therapy. Two out of 239 (0.8%) enrolled children, both thrombocytotic and with other acquired risk factors, developed thrombosis. In conclusion, reactive thrombocytosis in children aged 1 up to 24 months is frequent and unrelated to markers of disease activity or degree of inflammation.

The aims of the present study were to evaluate in a cohort of mothers infected with hepatitis C virus (HCV) the prevalence of HCV infection of their sexual partners, the influence of infection of the partners on perinatal transmission, and whether this influence is mediated by other well known risk factors for perinatal transmission. Forty-nine consecutive mothers infected with HCV who transmitted infection to their offspring and, as a control group, 557 consecutive mothers infected with HCV who did not transmit infection, together with their children and the fathers of the children who were also the sexual partners of the mothers were evaluated. History of intravenous drug use was significantly more frequent in women with partners infected with HCV than in women with partners not infected [115/180 (63.9%) vs. 87/401 (21.7%); relative risk (RR): 6.38, 95% confidence intervals (CI): 4.34–9.39, P

The aims of the study were to evaluate the economic burden of hospitalisations due to varicella in an Italian paediatric hospital during a 1-year period and to compare the data with potential expenses projected for a varicella mass vaccination programme.An observational, retrospective, cohort study was designed to measure hospital admission costs in a cohort of paediatric patients with varicella in a 12-month period. A cost comparison with a vaccination programme planned to prevent varicella in a whole birth cohort was performed. All children 0-16 years referred to the Anna Meyer Children's Hospital (AMCH) were considered. Since AMCH is a tertiary-level hospital and accept patients from other Italian regions, in order to avoid overestimation of hospitalisation expenses, all analyses pertaining to both vaccination and hospitalisation costs were uniquely calculated on the basis of the cohort of residents in the district of Florence.A total of 279 children were examined in the emergency department for varicella; 47/279 (16.8%) were sent to the inpatient clinic. The highest rate of hospitalisation (85.1%) was found in children4 years of age, and the largest number of complications (87.2%) occurred in previously healthy children. Mean length of hospitalisation (5.7 +/- 0.6 days) was similar to that reported in other western countries.Excluding any indirect cost, permanent sequelae and serious outcomes such as death, hospital expenses (corresponding to euro239 654 in a 1-year period), would account for around 80% of total expenses for vaccinating an entire birth cohort (euro310353).

Infants born from mothers with multiple blood-borne viral infections are at risk of multiple transmissions. Whether the risk of transmission of multiple infections increases with the number of viruses infecting the mother is still unknown. The aim of this study was to describe the risk of mother-to-infant transmission of multiple infections from multi-infected mothers. Sixty-four pregnant women infected by at least two viruses among human immunodeficiency virus-type 1 (HIV-1), hepatitis C virus, TT virus, and GB virus type C, together with their 64 infants, were studied. Maternal blood samples were collected in the third trimester of pregnancy and all infants were prospectively followed for evaluation of transmission within 3 months after birth and two times in the subsequent 24 months. Transmission of single and of dual infection from mothers infected by two viruses was, respectively, 10/40 (25%) and 5/40 (12.5%) and from mothers infected by three viruses 9/20 (45%) and 2/20 (10%). One (25%) infant infected by one virus was born from the four mothers infected by four viruses. Transmission of single or dual infection was not significantly associated with the number of viruses infecting the mother (P = 0.9) in the linear regression analysis. Present study suggests the absence of a synergistic effect from viral interactions toward mother-to-infant transmission of multiple infections and supports the hypothesis that transmission from multi-infected mothers is the result of the specific interaction between each virus and the host. These observations may be of clinical relevance in perinatal counseling.

Vertical transmission is the most common route of hepatitis C virus (HCV) infection in children. Transmission risk factors have been described, but most risk factors can only be evaluated using expensive laboratory exams. The aim of the present study was to evaluate whether maternal alanine transaminase (ALT) levels before pregnancy correlate with HCV vertical transmission. Seventy-four transmitting and 403 nontransmitting mothers were evaluated. All mothers enrolled had two ALT determinations in the last year before pregnancy, at least 6 months apart. Mothers were divided into two groups: mothers with persistently normal serum ALT levels and mothers with abnormal ALT levels. In the second group both mothers with constantly raised or with fluctuating ALT levels (one normal and one raised determination) were included. ALT was defined as raised if higher than twice the upper limit of normal. Abnormal ALT levels were found in 39/74 (52.7%) HCV transmitting mothers and in 146/403 (32.6%) nontransmitting mothers (P = 0.008; relative risk 1.96; 95% confidence limits 1.19–3.23). The risk of transmission from mothers with constantly raised ALT levels was more evident than that from mothers with fluctuating ALT levels. Increased ALT levels may reflect a more severe liver disease and a higher viral load, factors known to be associated with vertical transmission. ALT determination, a simple, widely available and inexpensive test, may help in identifying mothers with an increased risk of HCV vertical transmission. J. Med. Virol. 78:911–914, 2006. © 2006 Wiley-Liss, Inc.

Perinatal transmission of HCV is the main route of acquisition of HCV infection in children. Few studies have explored the mechanism of perinatal transmission, but a key role in transmission has been attributed to maternal viraemia. A new study now provides insights on the biological basis of this association.

Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed firstly in adults. In recent years, a number of direct-acting antiviral agents (DAAs) are under development for treatment of chronic hepatitis C virus (HCV) infection. These agents block viral replication inhibiting directly one of the several steps of HCV lifecycle. DAAs are classified into several categories based on their molecular target: HCV NS3/4A protease inhibitors, HCV NS5B polymerase inhibitors and HCV NS5A inhibitors. Other promising compounds are cyclophilin A inhibitors, mi-RNA122 and IFN-λ. Several new drugs associations will be developed in the near future starting from the actual standard of care. IFN-based and IFN-free regimens are being studied in adults. In this constantly evolving scenario new drug regimens targeted and suitable for children would be possible in the next future. Especially for children, it is crucial to identify the right combination of drugs with the highest potency, barrier to resistance and the best safety profile.

In children, clinical recognition of stroke and determination of its exact etiology are extremely difficult. The authors described a case of cryptogenic stroke in a 14-year-old-boy with asymptomatic atrial septal defect and hypercoagulable state. Paradoxical embolism was hypothesized as the responsible etiopathological mechanism. It is crucial to increase clinician awareness of stroke in children.

The perinatal transmission of hepatitis C virus (HCV) is the major route of infection in infants. The understanding of the risk factors of perinatal infection and the continuation of studies in this area allow one to propose immunological algorithms of prediction and to work outa follow-up strategy of infected children. The authors have made virological and Immunological studies of infants born to mothers with HCV infection.

In 1998, Edwards and Nelson discussed whether asphyxia at birth really is an important cause of neonatal encephalopathy and wondered how often neurological impairment in children is due to perinatal hypoxia-ischaemia and how often to entirely different causes.1 We describe two cases of neonatal intoxication resulting from the administration of local anaesthetic to the mother during labour but which we initially diagnosed as perinatal asphyxia. We analyse here the major manifestations of acute poisoning in newborns and the clinical picture that could be misdiagnosed as perinatal asphyxia. Early and correct diagnosis is recommended for allowing adequate treatment and a positive outcome and for ruling out the medicolegal aspect of perinatal asphyxias (law courts often have to decide whether a child's neurological impairment is the result of mismanagement of labour, leading to asphyxia). Within minutes of birth, two full term neonates delivered vaginally presented sudden neurological and cardiac signs such as apnoea, bradycardia, seizures, and hypotonia. In both cases no evidence of fetal distress was noted, and the fetal monitoring was normal. They were transferred to our neonatal intensive care unit with a presumptive diagnosis of perinatal asphyxia. ### Case 1 A 3550 g male infant was born after an uneventful pregnancy; episiotomy was performed after application of combined lidocaine (2.5%) and prilocaine (2.5%) cream. The Apgar score was high (9 at one minute, 9 at five minutes). Thirty minutes after birth, while still in the delivery room, the neonate suddenly developed apnoea, bradycardia, and hypotonia. He was intubated and mechanically ventilated. His cardiorespiratory function gradually improved, and he was extubated 30 minutes later. However, at this stage he began to show the first signs of neurological involvement, characterised by generalised hypertonia, which required transfer to our neonatal intensive care unit. During transport (at age one and a half hours) he had tonic …

We describe a 10-day-old infant with aseptic meningitis caused by varicella zoster virus, a very rare neonatal condition, associated with Escherichia coli sepsis. A 3420 g male neonate was delivered by caesarean section at 36 weeks after spontaneous rupture of the membranes. Apgar score was 91–95. Twenty hours later the previously healthy mother experienced an erythematous, vesicular pustular rash with high fever (40 C). Without any specific diagnosis, claritromicine was administered. The infant was breast-fed and discharged on day 4. On day 9, an erythematous rash appeared on the infant’s scalp and face and then extended in a craniocaudal direction. Treatment with claritromicine was commenced. On day 12, the newborn suddenly became pale, lethargic, subfebrile and cyanotic. He was admitted to another hospital where he experienced generalised tonic-clonic seizures. Phenobarbital was administered just before transferral to our neonatal intensive care unit (NICU). On inspection, a diffuse erythematous maculopapular eruption, more evident in the caudal region, was noted (Fig. 1). The infant, who was lethargic, irritable, hypotonic and had a temperature imbalance, required 40% oxygen administration. A slight neck stiffness was noted; however, the anterior fontanelle was not bulging. Laboratory studies showed a white blood cell count of 3700 cells/mm with an automated differential cell count of 40% neutrophils, 56% lymphocytes, 3% monocytes, and 2% eosinophils. C-reactive protein was 12 mg/dl. Serum electrolytes and arterial blood gas analysis were within the reference range, as were the CSF parameters (3 cells/mm, glucose level 86 mg/dl with serum glucose 156 mg/dl, protein level 64 mg/dl). The CSF was clear and no bacteria were observed on gram-stained smears. A chest X-ray film demonstrated bilateral interstitial pneumonia. Electroencephalograms showed inconstant interhemispheric asymmetry and a cerebral ultrasound failed to reveal any specific abnormalities. Ampicillin, gentamicin, acyclovir and varicella zoster virus (VZV) specific antibodies were administered. Further laboratory studies included bacterial cultures, serum antibody titres and polymerase chain reaction (PCR) in CSF for some human herpes viruses (cytomegalovirus, herpes simplex virus, VZV), coxackie and parvovirus. Blood, urine and skin grew Escherichia coli, whereas the CSF culture was negative. VZV DNA was detected in CSF by PCR. Seroconversion of anti-VZV IgG and IgM was positive in both the infant’s and the maternal peripheral blood. Antimicrobial and antiviral treatment was continued for 14 days. Within 24 h, lethargy and hypotonia resolved M. S. Pignotti (&) AE G. Indolfi AE G. Donzelli Neonatal Intensive Care Unit, Anna Meyer Children’s Hospital, via Luca Giordano 13, 50132 Firenze, Italy E-mail: m.pignotti@meyer.it Tel.: +39-55-5662432 Fax: +39-55-702856