Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study.

OBJECTIVES: To prospectively describe the epidemiology and long-term outcome of childhood-acquired hepatitis C virus (HCV) infection in a large cohort of children followed at a single center. METHODS: All children with chronic HCV infection followed at the Liver Unit of our tertiary Hospital in Florence (Italy) from January 1, 1988, to September 30, 2021, were included in the analysis. RESULTS: The final sample consisted of 163 children (median age at enrollment 4 years, interquartile range (IQR): 10; median age at last follow-up 14 years, IQR: 7). The median duration of follow-up was 86 months (IQR: 112). One hundred twenty-five children were vertically infected and 26 acquired the infection horizontally. Twenty-six of the 125 children who were vertically infected (20.8%) underwent spontaneous clearance of HCV RNA at a median age of 4 years (IQR: 2), whereas all the others remained persistently viremic. One patient was diagnosed with cirrhosis; 2 presented clinically detectable extrahepatic manifestations (chronic urticaria). Thirty-two children (19.6%) received antiviral therapy: 8 out of 32 (25%) were treated with pegylated-interferon alfa-2b [sustained virological response (SVR) 24 weeks after the end of treatment in 7/8]; 24 out of 32 (75%) were treated with direct-acting antivirals (SVR 12 weeks after the end of treatment in 23/24). CONCLUSIONS: The present study describes the largest cohort of children with chronic HCV infection prospectively evaluated with a long follow-up at a single center. HCV infection in children is often a chronic infection that can be cured with modern antiviral therapy. Early treatment could prevent the development of advanced liver disease.

Chronic hepatitis B in children, report of a single-centre longitudinal study on 152 children.

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.

Hepatitis co-infection in paediatric HIV: progressing treatment and prevention.

PURPOSE OF REVIEW: To analyse the main evidence and recommendations for the management of hepatitis co-infection in children living with HIV. RECENT FINDINGS: We analysed available data pertaining to the natural history of liver disease and treatment of co-infected children. SUMMARY: Viral hepatitis co-infection in people living with HIV (PLHIV) is a global problem owing to the shared routes of transmission, particularly in areas of high endemicity for the three viruses. Viral hepatitis co-infection can accelerate liver disease progression and increase morbidity and mortality, even in patients on suppressive antiretroviral treatment (ART). Viral hepatitis should be routinely screened in PLHIV and, once diagnosed with viral hepatitis, PLHIV should be closely monitored for liver disease progression and complications. Children living with HIV-HBV co-infection should be treated with ART containing agents which are active against both viruses. Children living with HIV-HCV co-infection should receive directly acting antivirals (DAA) to eradicate HCV infection. Prevention measures to reduce vertical and horizontal transmission of HBV and HCV (anti-HBV vaccination and immunoglobulins, anti-HBV treatment in pregnancy, anti-HCV DAAs in people of childbearing age, avoiding blood contact, sexual barrier precautions) should be adopted and encouraged, particularly in high endemicity countries.

Paediatric-onset autoimmune liver disease: Insights from a monocentric experience.

BACKGROUND: Autoimmune liver disease (AILD) encompasses autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC) and primary sclerosing cholangitis (PSC). A unified disease process evolving over time through these entities has been recently suggested. From this perspective, this study aimed to compare the characteristics of childhood-onset AILD at baseline and after a medium-to-long term follow-up period. METHODS: Paediatric-onset cases of AILD diagnosed between 1992 and 2023 at a tertiary-care centre were reviewed. Patients transitioned to adult-care by the time of data collection were asked for clinical updates. RESULTS: Fifty-five patients were included (AIH = 20, ASC =22, PSC =13). AIH, ASC and PSC exhibited increasing age at the onset (AIH to PSC, p < 0.01). The area under the receiver operating characteristic curve for gamma-glutamyltranspeptidase (GGT) combined with alkaline phosphatase/aspartate aminotransferase (ALP/AST) ratio in predicting sclerosing cholangitis was 0.94, with a sensitivity of 86 % and a specificity of 94 %. At the last follow-up (median duration 5,8 years, interquartile range [IQR] 2,9-10,2, n = 45), 15 patients (33 %) developed portal hypertension, 2 patients (4 %) underwent liver transplantation, no patient died. CONCLUSION: A cohort of childhood-onset AILD managed at a single centre reveals a temporal trend in the onset of AIH, ASC and PSC, with progressively older ages. Elevated GGT levels combined with a high ALP/AST ratio predict the diagnosis of sclerosing cholangitis. The occurrence of liver-related adverse events in one-third of patients highlights the progressive nature of paediatric-onset AILD.

Analysis of a Cohort of 165 Pediatric Patients with Human Bocavirus Infection and Comparison between Mono-Infection and Respiratory Co-Infections: A Retrospective Study.

INTRODUCTION: Human Bocavirus (HBoV) is mainly associated with respiratory tract infections. However, its role as respiratory pathogen is not fully understood for a high co-infection rate in symptomatic patients and a significant HBoV detection rate in asymptomatic subjects. This study aimed to describe a large cohort of children with HBoV infection and to compare HBoV mono-infection and co-infections. METHODS: We retrospectively reviewed data from 165 children admitted to Meyer Children's Hospital IRCCS from March 2022 to March 2023 with the diagnosis of HBoV infection, detected using Reverse Transcription qPCR from nasal swabs. Thereafter, we compared patients with HBoV mono-infection (Group A) and those with HBoV co-infections (Group B) in terms of disease severity, established by the length of stay (LOS), the requirement of Pediatric Intensive Care Unit (PICU), and advanced respiratory support (ARS). RESULTS: The median age was 1.5 years; 80% of patients presented with respiratory symptoms. The discharge rate from the emergency department (ED) within 24 h was 42.4%. Most cases (57.6%) were hospitalized, and 7.3% were admitted to PICU due to respiratory failure. Group A comprised 69 patients, and Group B 96 children (95% viral co-infections, 2% bacterial, 3% viral and bacterial). Group A and Group B were similar in hospitalization rate but differed significantly in LOS (median 3 vs. 5 days) and requirement of PICU admission (0 vs. 12 patients, p < 0.001). Patients with a respiratory disease history (17.5%) showed significantly longer LOS and more necessity of inhaled bronchodilator therapy. CONCLUSIONS: HBoV should be considered a relevant respiratory pathogen especially in viral co-infections. Patients with HBoV co-infections have a higher risk of necessitating advanced respiratory support with more PICU admission and longer LOS; a previous respiratory disease puts them at a higher risk of longer hospitalization.

Update on Fever of Unknown Origin in Children: Focus on Etiologies and Clinical Approach.

Fever of unknown origin (FUO) can be caused by four etiological categories of diseases. The most common cause of FUO in children is represented by infections, followed by inflammatory conditions and neoplastic causes; a decreasing quote remains still without diagnosis. Despite the fact that several diagnostic and therapeutic approaches have been proposed since the first definition of FUO, none of them has been fully validated in pediatric populations. A focused review of the patient's history and a thorough physical examination may offer helpful hints in suggesting a likely diagnosis. The diagnostic algorithm should proceed sequentially, and invasive testing should be performed only in select cases, possibly targeted by a diagnostic suspect. Pioneering serum biomarkers have been developed and validated; however, they are still far from becoming part of routine clinical practice. Novel noninvasive imaging techniques have shown promising diagnostic accuracy; however, their positioning in the diagnostic algorithm of pediatric FUO is still not clear. This narrative review aims to provide a synopsis of the existent literature on FUO in children, with its major causes and possible diagnostic workup, to help the clinician tackle the complex spectrum of pediatric FUO in everyday clinical practice.

COVID-19 and Thromboembolic Events in the Pandemic and Pre-Pandemic Era: A Pediatric Cohort.

The Coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been variably associated with thromboembolic events (TEs) in children. The aim of our study was to assess the prevalence of TEs in children hospitalized during a five-year period in a tertiary pediatric hospital, particularly in patients with COVID-19 and MIS-C. Overall, 38 patients were discharged with the diagnosis of TE: 20 in the pre-pandemic and 18 in the pandemic period. The prevalence of TEs was the same (0.08%) in the pre-pandemic and pandemic periods. The occurrence of TEs was higher in patients with COVID-19 or MIS-C (6/517, 1.16%) when compared to children without these conditions in the pandemic and in the pre-pandemic periods. The prevalence of TEs in children with MIS-C was significantly higher than the prevalence in patients with COVID-19. Five out of six of the patients with COVID-19 or MIS-C developing a TE had at least one predisposing factor to thrombosis. In conclusion, our study shows an increased prevalence of TEs in children hospitalized with COVID-19 or MIS-C, if compared to children without COVID-19 or MIS-C in the pandemic period and in the pre-pandemic period. The prevalence of TEs was significantly higher in patients with MIS-C.

Treatment of hepatitis B virus infection in children and adolescents.

Hepatitis B virus (HBV) infection is one of the main causes of morbidity and mortality worldwide. Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection, with normal or only slightly raised aminotransferases. Although a conservative approach in children is usually recommended, different therapies exist and different therapeutic approaches are possible. The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma, although these complications are rare in children. Both United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) have approved interferon alfa-2b for children aged 1 year and older, pegylated interferon alfa-2a and lamivudine for children aged 3 years and older, entecavir for use in children aged 2 years and older, and adefovir for use in those 12 years of age and older. Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by US-FDA for treatment in children aged 12 years and older. Finally, EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age. This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

An Unusual Case of Hypoproteinemia in Childhood: Keep in Mind Trichobezoar.

Protein-losing enteropathy (PLE) is a rare condition characterized by protein loss through the gastrointestinal tract, leading to hypo-proteinemia. Patients may be asymptomatic or present with variety of complications of hypoproteinemia (e.g., oedema, ascites, pleural, and cardial effusions). We describe a case report of a young girl suffering from behavioral disorder since childhood who presented with generalized oedema, hypoproteinaemia, and microcytic hypochromic anemia. In addition, the girl had an intervention for jejunal atresia and intestinal malrotation in her past medical history. Upper gastrointestinal endoscopy revealed a trichobezoar extending from stomach into the small bowel, thus classified as Rapunzel Syndrome (RS), causing mechanical obstruction of intestinal lumen and intestinal lymphatic drainage resulting in a protein-losing enteropathy (PLE). Trichobezoar was successfully removed by a surgical laparotomy resulting in resolution of symptoms and normalization of biochemical parameters. Possibly, previous surgery might have had an influence on intestinal dysmotility and trichobezoar formation. PLE is a very rare presenting symptom of RS, developing as result of intestinal obstruction caused by large trichobezoars. RS has to be considered in patients, especially adolescents, suffering from behavior disorder as trichotillomania and trichophagia. Surgical removal and nutritional supplementation are the gold treatment of large trichobezoar.