Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. Two types of paediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (anti-LKM-1/anti-LC-1; AIH-2).Pertinent issues addressing the diagnosis, treatment and long term follow up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate and Mendeley databases over the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

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Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical and early childhood transmission are the main routes of HBV transmission globally, responsible for most chronic infectionsincluding in adults who bear the greatest burden of morbidity and mortality. Universal infant and birth dose hepatitis B immunization is the key preventative strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections. Global progress on HBV testing and treatment, however, has been slow in adults and children. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HBV infection in adolescents and children, highlighting key differences from the experience with adults, and conclude with key actions to address current policy gaps. The estimated global prevalence in children aged 5 years or less is 1.3%. Most children are in the "high replication, low level of inflammation" infection phase with normal or only minimally raised aminotransferases; cirrhosis and hepatocellular carcinoma are rare. Although entecavir is approved and recommended for children 2 to <18 years, and tenofovir for those 12 to < 18 years, a conservative approach to treatment initiation is currently recommended. Key actions to address current policy gaps include: validation of non-invasive tests for liver disease staging; additional immunopathogenesis studies in HBV infected children, and long-term follow-up of children on nucleoside analogue regimens to inform guidance on when to start treatment; evaluation of different treatment strategies for children with high levels of replication; and establishment of paediatric treatment registries and international consortia to promote collaborative research.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have now transformed treatment for HCV infection. Since the launch in 2016 of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on treatment of adults, who bear the greatest burden of morbidity and mortality of HCV related chronic liver disease. There has been much less attention paid to addressing response to HCV in children and adolescents, in part because of the lack of data to inform specific paediatric management practices and policy. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden in children aged 1 to 19 years is 0•15% and 3•5 (3•1-3•9) million, respectively. HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir, ledipasvir and ribavirin have now received regulatory approval and guidelines recommend their use in adolescents ages >12 years with HCV infection. Key actions to address the current policy gaps and achieve treatment scale-up comparable to that in adults include: establishment of a testing and treatment access campaign targeted at children and adolescents; fast-track evaluation of pangenotypic regimens and accelerated approval of paediatric formulations. Research gaps that need to be addressed include age-specific seroprevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agenda.

BackgroundPneumococcal serotyping is usually performed by Quellung reaction, considered the gold standard test. However the method cannot be used on culture-negative samples. Molecular methods can be a useful alternative. The aim of the study was to evaluate the use of Multiplex-sequential-PCR (MS-PCR) or Realtime-PCR on blood samples for diagnosis and serotyping of invasive pneumococcal disease (IPD) in a pediatric clinical setting.Methodology/Principal FindingsSensitivity and specificity of MS-PCR and Realtime-PCR have been evaluated both on 46 well characterized pneumococcal isolates and on 67 clinical samples from children with culture-negative IPD. No difference in sensitivity and specificity between MS-PCR and Realtime PCR was found when the methods were used on isolates: both methods could type 100% isolates and the results were always consistent with culture-based methods. On the contrary, when used on clinical samples 43/67 (64.2%) were typeable by MS-PCR and 61/67 (91.0%) by Realtime-PCR (p = 0.0004,K Cohen 0.3, McNemar's p<0.001). Non-typeability by MS-PCR was associated in 18/20 cases (90.0%) with low bacterial load. The difference between the two methods was present both when they were used on normally sterile fluids (respectively 31/33 (93.9%) typeable samples for Realtime-PCR and 24/33 (72.7%) for MS-PCR, p = 0.047, 95%CL 0.03–0.98; K Cohen 0.3; McNemar's p = 0.0016) and when they were used on nasopharyngeal swabs (respectively 30/34 (88.2%) typeable samples for Realtime-PCR and 19/34 (55.9%) for MS-PCR, p = 0.007, 95%CL 0.04–0.66); the presence of multiple pneumococcal serotypes in nasopharyngeal swabs was found more frequently by Realtime PCR (19/30; 63.3%) than by Multiplex-sequential PCR (3/19; 15.8%; p = 0.003;95%CL 1.87–39.97).Conclusions/SignificanceIn conclusion, both MS-PCR and Realtime PCR can be used for pneumococcal serotyping of most serotypes/serogroups directly on clinical samples from culture-negative patients but Realtime-PCR appears more sensitive.