Inadequate Hospital Practices to Prevent Mother-to-Child Transmission of Hepatitis B Virus Infection: A European Survey.

Objectives: Prevention of vertical transmission of hepatitis B virus (HBV) infection is crucial to eliminate viral hepatitis as a major public health threat by 2030. We aimed to assess the current hospital policies and practices implemented before, at, and after birth, and to evaluate potential barriers to the full application of international guidelines.

Methods: A web-based survey was supported by PENTA Foundation and distributed across Europe from October to December 2021.

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.

Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee.

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age.

Case numbers of acute hepatitis of unknown aetiology among children in 24 countries up to 18 April 2022 compared to the previous 5 years.

An increase of acute hepatitis of unknown aetiology has been reported among children in multiple countries worldwide. With a rapid online survey among hospitals in and outside of Europe, we describe case numbers recorded from 1 January to 18 April 2022 vs the previous 5 years. Of 24 countries that responded, we identified 5/17 European and 1/7 non-European countries with an elevation in probable cases of unexplained acute hepatitis, and severe cases were elevated in five European countries.

Proceedings of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition Monothematic Conference, 2020: "Acute Liver Failure in Children": Treatment and Directions for Future Research.

Objectives: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology.

Methods: The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved.

Proceedings of ESPGHAN Monothematic Conference 2020: "Acute Liver Failure in Children": Diagnosis and Initial Management.

Objectives: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children.

Methods: The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece.

NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency.

Purpose: Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system.

Methods: Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system.

Sofosbuvir/velpatasvir for the treatment of hepatitis C in pediatric patients.

: Sofosbuvir/velpatasvir is a combination of direct-acting antivirals with pangenotypic activity for treatment of chronic hepatitis C virus infection. It was approved in 2020 for use in children aged 6-17 years and in June 2021 by the United States Food and Drug Administration for the age group 3-5 years.: A literature search of PUBMED and EMBASE was conducted on April 30th and updated on June 10th.

Breakthroughs and challenges in the management of pediatric viral hepatitis.

Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) major causes of advanced liver disease and mortality worldwide. Although regarded as benign infections in children, their persistence through adulthood is undoubtedly of concern. Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment, which is currently far from being curative.

SNPs of the IFNL favour spontaneous clearance of HCV infection in children.

Background: Both spontaneous and treatment-induced clearance of hepatitis C virus (HCV) in adults have been associated with genetic polymorphisms in the interferon-λ genes. The aim of the present study was to confirm the association between the rs12979860 and evaluate the association between the rs368234815 and the rs4803217 single-nucleotide polymorphisms (SNPs) of the interferon-λ genes and the outcome of the infection in children.

Methods: Alleles and genotypes frequencies of 32 children, who presented spontaneous clearance of the virus and 135 children, with viral persistence were compared with ethnically matched controls obtained from the 1000 Genomes Project and the International HapMap Project databases.

Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report.

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot-Marie-Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients.

Case Presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months.

Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene.

Efficacy of Sofosbuvir/Ledipasvir in Adolescents With Chronic Hepatitis C Genotypes 1, 3, and 4: A Real-world Study.

Objectives: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to <18 years old) with CHC in the real-world setting.

Methods: Prospective, open-label, multicentre study involving 12 Italian centres.

Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection.

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.

Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents: A Position Paper of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Objective: This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement.

Methods: MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019.

Results: A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper.

Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies.

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition.

Shortened 8-Week Course of Sofosbuvir/Ledipasvir Therapy in Adolescents With Chronic Hepatitis C Infection.

Treatment-naïve, noncirrhotic adults with chronic hepatitis C virus genotype 1 infection and with viremia levels <6 million IU/mL could be effectively treated with sofosbuvir/ledipasvir for 8 weeks. The aim of this pilot, prospective, open-label, multicenter study was to evaluate the efficacy and safety of this shortened treatment course in adolescents (≥12 years). The efficacy endpoint was sustained virological response 12 weeks after the end of treatment.

Hepatitis B virus infection in children and adolescents.

Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical (mother-to-child) and horizontal early childhood transmission are the main routes of HBV transmission and are responsible for most chronic infections, including among adults who bear the greatest burden of morbidity and mortality. Universal hepatitis B immunisation at birth and in infancy is the key strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections.

Hepatitis C virus infection in children and adolescents.

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 transformed treatment for HCV infection. Since the 2016 launch 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 the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease.

Treatment and monitoring of children with chronic hepatitis C in the Pre-DAA era: A European survey of 38 paediatric specialists.

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.

Hepatitis C Genotype 4 Virus Nonstructural 3 and Nonstructural 5A Resistance-associated Substitutions in a 16-year-old Adolescent Failing Ombitasvir/Paritaprevir/Ritonavir Plus Ribavirin.

Preexistence and appearance of resistance-associated substitutions limit the efficacy of direct-acting antivirals in treatment of hepatitis C. This is the first case report of an adolescent with chronic hepatitis C virus genotype 4 infection and cirrhosis who failed treatment with ombitasvir/paritaprevir/ritonavir and ribavirin. Resistance analysis showed baseline resistance-associated substitutions M28V and Y93C and emergent D168H.

Advanced liver disease in Russian children and adolescents with chronic hepatitis C.

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.

Treatment of Adolescents With Chronic Hepatitis C Virus Infection: New Regimen on the Block.

Editorial to Leung et al. "Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4".