Daniele Serranti

Interleukin 28B rs12979860 single-nucleotide polymorphism predicts spontaneous clearance 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.

Underestimation of Invasive Meningococcal Disease in Italy

Underestimation is attributable to misdiagnosis, especially in fatal cases, and use of insufficiently sensitive laboratory methods.

New treatments for chronic hepatitis C: an overview for paediatricians.

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.

A kwashiorkor case due to the use of an exclusive rice milk diet to treat atopic dermatitis.

Although several cases of severe hypoalbuminemia resulting from rice milk have been described in the past, today the use of rice milk without nutritional counseling to treat eczema is still a continuing, poor practice. We describe a kwashiorkor case in an infant with severe eczema exclusively fed with rice milk. It is well documented that rice milk is not a sufficient protein source. Moreover, only a small portion of eczema is triggered by food allergy. In conclusion this case raises the importance of managing dietary changes facing food allergies with responsibility for specialized consensus among pediatricians, nutritionists, endocrinologists and allergists all of them specialist professionals.

Hepatitis C in Children Co-infected With Human Immunodeficiency Virus.

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-&agr; 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.

Antibiotic induced liver injury: what about children?

Abstract Antimicrobial agents are important causes of drug-induced liver injury. They are responsible for about 45% of cases of drug hepatotoxicity. Hepatic damage mechanisms are intrinsic or idiosyncratic. Usually, antibiotics are responsible for idiosyncratic toxicity. This review summarizes the rate of incidence and clinical features of hepatotoxicity due to antibiotics and chemotherapics, with particular attention to data regarding paediatric population. Liver injury features have been systematically evaluated for the most commonly administered antibiotics and chemotherapics in adults, even though there is little information about other widely used compounds, as cephalosporine or clarithromycin, and about antibiotics active against multi-resistant bacteria, as carbapenems, vancomycin, clindamycin, and linezolid. By contrast, there is an abundance of case reports in paediatrics, but very few structured studies have been carried out in children. Children are an important class of antibiotic users, with specific metabolic characteristics, so more studies on them should be carried out.

Transient Hypothyroidism and Autoimmune Thyroiditis in Children with Chronic Hepatitis C Treated with Pegylated-interferon-α-2b and Ribavirin

Background: Autoimmune thyroid disease and thyroid dysfunction are common in adults receiving interferon (IFN)-based treatment for chronic hepatitis C (CHC). Few data are available in children with CHC. This study is aimed to evaluate the appearance and timing of thyroid dysfunction and antithyroid autoimmunity in children with CHC treated with pegylated IFN-&agr;-2b and ribavirin (RBV). Methods: Sixty-one otherwise healthy children with CHC, 3–17 years of age, infected perinatally and treatment naïve, receiving therapy with pegylated IFN-&agr;-2b and RBV and 183 age- and sex-matched controls were included in a multicenter, prospective, case-control study. Thyroid-stimulating hormone, free thyroxine, antithyroglobulin antibodies and antithyroid peroxidase antibodies were assessed before, during and 24 weeks after the end of treatment. Results: From baseline to the end of treatment, subclinical hypothyroidism and autoimmune thyroiditis were diagnosed in 17 of 61 (27.94%) and in 4 of 61 (6.6%) of the children treated, respectively, and in 5 of 183 (2.7%) and in none of the controls (P < 0.0001, relative risk: 10.2, 95% confidence interval: 3.9–26.5; P = 0.03, relative risk: 26.8, 95% confidence interval: 1.5–489.1, respectively). Twenty-four weeks after the end of treatment, subclinical hypothyroidism persisted in only 4 of 61 (6.6%). Autoimmune thyroiditis persisted in 3 of 4 (75%) of the cases. Conclusions: Subclinical hypothyroidism is common in children with CHC receiving treatment with pegylated IFN-&agr;-2b and RBV, but in most cases is transient. Autoimmune thyroiditis, which is less common, generally persists after treatment completion. Thyroid function should be carefully monitored in patients presenting with antithyroid autoantibodies and thyroid dysfunction during and after pegylated IFN-&agr;–based treatment.

Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission

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.

Direct-acting antivirals for children and adolescents with chronic hepatitis C

In 2017, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved the fixed-dose direct-acting antiviral (DAA) combination sofosbuvir and ledipasvir and the combination sofosbuvir plus ribavirin for the treatment of adolescents (aged 12-17 years) with chronic hepatitis C. Preliminary results on the use of DAAs in paediatric patients are available for the fixed-dose combination sofosbuvir and ledipasvir in children aged 6-17 years for genotype 1 or 4 infection; for combination sofosbuvir plus ribavirin for adolescents aged 12-17 years for genotype 2 or 3 infection; for the fixed-dose combination ombitasvir, paritaprevir, and ritonavir with or without dasabuvir and with or without ribavirin for adolescents aged 12-17 years with genotype 1 or 4 infection; and for the combination of sofosbuvir plus daclatasvir for children with genotype 4 infection. All the results available indicated positive efficacy and favourable safety profiles of the different combinations of DAAs. With the approval of the new drugs, indications for treatment of children with chronic hepatitis C have changed. DAA therapy is recommended for all adolescents aged 12-17 years with chronic hepatitis C virus infection independent of treatment history and disease severity. If and when DAAs are approved for younger age cohorts, all children older than 3 years infected with hepatitis C will benefit from antiviral therapy. In this Review, we aim to provide an up-to-date overview of the existing evidence on the paediatric use of DAAs, summarising indications to treatment and recommendations for monitoring.