|
1
|
Stinco M, Rubino C, Bartolini E, Nuti F, Paolella G, Nebbia G, Silvestro E, Garazzino S, Nicastro E, D'Antiga L, Zanchi C, Morra L, Iorio R, Di Dato F, Maggiore G, Sartorelli MR, Comparcola D, Stracuzzi M, Giacomet V, Musto F, Pinon M, Calvo P, Carloni I, Zallocco F, Cananzi M, Trapani S, Indolfi G. Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study. Liver Int 2025; 45:e16180. [PMID: 39569493 PMCID: PMC11897846 DOI: 10.1111/liv.16180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 10/16/2024] [Accepted: 11/11/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND & AIMS Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC. METHODS This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data. RESULTS Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment. CONCLUSIONS This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.
Collapse
Affiliation(s)
| | - Chiara Rubino
- Liver UnitMeyer Children's Hospital IRCCSFlorenceItaly
| | | | - Federica Nuti
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Giulia Paolella
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Gabriella Nebbia
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Erika Silvestro
- Pediatric Infectious Diseases Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Silvia Garazzino
- Pediatric Infectious Diseases Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Emanuele Nicastro
- Hepatology, Gastroenterology and Transplantation UnitHospital Papa Giovanni XXIIIBergamoItaly
| | - Lorenzo D'Antiga
- Hepatology, Gastroenterology and Transplantation UnitHospital Papa Giovanni XXIIIBergamoItaly
| | - Chiara Zanchi
- Institute for Maternal and Child Health–IRCCS Burlo GarofoloTriesteItaly
| | - Laura Morra
- Pediatric DepartmentUniversity of TriesteTriesteItaly
| | - Raffaele Iorio
- Department of Translational Medical Science, School of Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
| | - Fabiola Di Dato
- Department of Translational Medical Science, School of Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
| | - Giuseppe Maggiore
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Maria Rita Sartorelli
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Donatella Comparcola
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Marta Stracuzzi
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Vania Giacomet
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Francesca Musto
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Michele Pinon
- Pediatric Gastroenterology Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Pierluigi Calvo
- Pediatric Gastroenterology Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Ines Carloni
- Pediatric Infectious Disease UnitSalesi Children HospitalAnconaItaly
| | - Federica Zallocco
- Pediatric Infectious Disease UnitSalesi Children HospitalAnconaItaly
| | - Mara Cananzi
- Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of Children with Liver TransplantationUniversity Hospital of PadovaPadovaItaly
| | - Sandra Trapani
- Pediatric UnitMeyer Children's Hospital IRCCSFlorenceItaly
- Department of Health SciencesUniversity of FlorenceFlorenceItaly
| | - Giuseppe Indolfi
- Liver UnitMeyer Children's Hospital IRCCSFlorenceItaly
- Department of NEUROFARBAUniversity of FlorenceFlorenceItaly
| |
Collapse
|
|
2
|
Dieye NL, Varol M, Zorich SC, Millen AE, Yu KOA, Gómez-Duarte OG. Retrospective analysis of vertical Hepatitis C exposure and infection in children in Western New York. BMC Gastroenterol 2023; 23:242. [PMID: 37460966 DOI: 10.1186/s12876-023-02871-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Accepted: 07/04/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Vertical transmission of hepatitis C virus (HCV) is the primary cause of hepatitis C in the pediatric population. Nonetheless, only a small proportion of HCV-exposed children are tested. This study aimed to measure the proportion of HCV-exposed children tested and infected in Western New York and to identify factors influencing the odds of testing and infection in this population. METHODS This was a 11-year retrospective chart review study in which clinical, demographic, and behavioral data for HCV-exposed children and their mothers were collected. This period included year 2019 when a hepatitis C program began promoting early hepatitis C screening among infants born to mothers positive for hepatitis C. PCR-based detection of hepatitis C was used for children under 18 months of age and antibody testing for children above 18 months of age, followed by PCR if the antibody testing was positive. Logistic regression models were used to determine which characteristics associate with testing and infection status. RESULTS From a total of 133 children evaluated in clinic for hepatitis C from 2011 to 2021, 96.2% (128/133) were seen from 2019 to 2021. Among the 133 HCV-exposed children in our sample, 72.1% (96/133) were tested for HCV, 62.4% (83/133) were tested by PCR, 9.0% (12/133) tested by antibody, and 5.2% (5/95) of those tested were infected. Only one child out of 12 was positive for hepatitis C antibody yet, subsequent PCR testing was negative in this child. Among all five hepatitis C infected children, four were diagnosed with neonatal abstinence syndrome, five had maternal history of illicit drug use, one had maternal history of HIV infection, and all of them were identified after the hepatitis C program open in 2019. The odds of a child being tested were lower for those accompanied by their biological mother at their clinic visit (odds ratio, 0.16; 95% CI, 0.06-0.45). CONCLUSIONS Screening programs on hepatitis C vertical transmission improved detection of hepatitis C among exposed children. The proportion of children born to mothers with hepatitis C in Western New York that were positive for hepatitis C was 5.2%, suggesting that similar proportion of exposed infants born before 2019 were lost for follow up.
Collapse
Affiliation(s)
- Ndeye Licka Dieye
- International Enteric Vaccine Research Program (IEVRP), Division of Pediatric Infectious Diseases, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Mine Varol
- International Enteric Vaccine Research Program (IEVRP), Division of Pediatric Infectious Diseases, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Shauna C Zorich
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Amy E Millen
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Karl O A Yu
- International Enteric Vaccine Research Program (IEVRP), Division of Pediatric Infectious Diseases, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
| | - Oscar G Gómez-Duarte
- International Enteric Vaccine Research Program (IEVRP), Division of Pediatric Infectious Diseases, The State University of New York (SUNY) at Buffalo, Buffalo, NY, USA.
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA.
| |
Collapse
|
|
3
|
Ades AE, Gordon F, Scott K, Collins IJ, Thorne C, Pembrey L, Chappell E, Mariné-Barjoan E, Butler K, Indolfi G, Gibb DM, Judd A. Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment. Clin Infect Dis 2023; 76:913-991. [PMID: 35396848 PMCID: PMC9989140 DOI: 10.1093/cid/ciac255] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. METHODS Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA-negative infants in whom RNA was not detectable until after 6 weeks. RESULTS Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1-18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0-76.9), 39.7% (CrI, 17.9-65.9), and 20.9% (CrI, 4.6-44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. CONCLUSIONS Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment.
Collapse
Affiliation(s)
- A E Ades
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Fabiana Gordon
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Karen Scott
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Intira Jeannie Collins
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Claire Thorne
- Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Lucy Pembrey
- Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Elizabeth Chappell
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Eugènia Mariné-Barjoan
- Public Health Department, Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, Nice, France
| | - Karina Butler
- Children’s Health Ireland at Crumlin and Temple Street, Dublin, Ireland
| | - Giuseppe Indolfi
- Meyer Children’s Hospital and Department Neurofarba, University of Florence, Firenze, Italy
| | - Diana M Gibb
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Ali Judd
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| |
Collapse
|
|
4
|
Stinco M, Bartolini E, Veronese P, Rubino C, Moriondo M, Ricci S, Trapani S, Azzari C, Resti M, Indolfi G. Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study. J Pediatr Gastroenterol Nutr 2022; 75:e2-e7. [PMID: 35653496 DOI: 10.1097/mpg.0000000000003481] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
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.
Collapse
Affiliation(s)
- Mariangela Stinco
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Elisa Bartolini
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Piero Veronese
- the Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Chiara Rubino
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Maria Moriondo
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
| | - Silvia Ricci
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
- the Department of Health Sciences, Pediatric Section, University of Florence
| | - Sandra Trapani
- the Department of Health Sciences, Pediatric Section, University of Florence
| | - Chiara Azzari
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
| | - Massimo Resti
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Giuseppe Indolfi
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
- the Department NEUROFARBA, University of Florence
| |
Collapse
|
|
5
|
Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
Collapse
Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| |
Collapse
|
|
6
|
Alqahtani SA, Colombo MG. Treating paediatric hepatitis C in the era of direct-acting antiviral agents. Liver Int 2021; 41:1189-1200. [PMID: 33533543 DOI: 10.1111/liv.14810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/09/2021] [Accepted: 01/28/2021] [Indexed: 02/13/2023]
Abstract
The prevalence and burden of hepatitis C virus (HCV) in children are poorly understood mainly as a result of the fact that studies in this population have largely been done in high-risk groups and in highly endemic regions. Epidemiological studies estimate the viraemic prevalence in the paediatric population aged 0-18 years at 0.13%, corresponding to 3.26 million children with HCV in 2018. While vertical transmission occurs in up to 5% of neonates born to infected mothers, with preference for those with high viral load and co-infection with the human immunodeficiency virus, injection drug use is the prevalent modality of HCV infection among adolescents. Notwithstanding the fact that HCV usually has an indolent course in children and adolescents, hepatitis C may progress to significant liver disease in a fraction of patients. The finding of severe disease or cirrhosis in a minority of paediatric patients with HCV underscores the importance of early diagnosis and treatment in order to prevent long-term morbidity. Universal screening of HCV in pregnant women is key to identify infants exposed to such a risk and link them to care. Recently, direct-acting antiviral drugs proved to be as safe and effective in young HCV patients as in adults, and these agents are now approved for treatment of paediatric patients as young as 3 years. This review provides a contemporary overview of the HCV disease burden in children, with a particular focus on its treatment in the era of direct-acting antiviral agents.
Collapse
Affiliation(s)
- Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA.,Liver Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | | |
Collapse
|
|
7
|
Melikoki V, Kourlaba G, Kanavaki I, Fessatou S, Papaevangelou V. Seroprevalence of Hepatitis C in Children Without Identifiable Risk-Factors: A Systematic Review and Meta-Analysis. J Pediatr Gastroenterol Nutr 2021; 72:e140-e148. [PMID: 33633077 DOI: 10.1097/mpg.0000000000003099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct-acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high-risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness. METHODS Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high-risk groups alone were excluded. RESULTS Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P < 0.001). CONCLUSIONS Considering probable underdiagnosis of HCV infection in children, this information reveals that prevalence is substantial. One may argue that future strategies aiming towards HCV elimination, may need to include antiviral treatment of pre-adolescent children as well.
Collapse
Affiliation(s)
| | - Georgia Kourlaba
- Center for Clinical Epidemiology and Outcomes Research (CLEO), Athens
| | - Ino Kanavaki
- Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine, University General Hospital ATTIKON, Athens, Greece
| | - Smaragdi Fessatou
- Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine, University General Hospital ATTIKON, Athens, Greece
| | - Vassiliki Papaevangelou
- Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine, University General Hospital ATTIKON, Athens, Greece
| |
Collapse
|
|
8
|
Rogers ME, Balistreri WF. Cascade of care for children and adolescents with chronic hepatitis C. World J Gastroenterol 2021;27:1117-1131. [PMID: 33828389 PMCID: PMC8006101 DOI: 10.3748/wjg.v27.i12.1117] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/19/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection presents a significant global public health burden. In 2015, over 400000 deaths worldwide were attributed to HCV infection. This led the World Health Organization (WHO) in 2016 to set the ambitious goal of eliminating HCV by 2030. Adult-centered guidelines have been established in order to provide direction for healthcare professionals, allowing integration of the newest screening policies and therapeutic strategies into their practices. However, for children and adolescents, HCV is a significant, unrecognized public health problem. HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic. An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States, with approximately 1700 of their infants being infected with HCV. Newer HCV-specific therapeutics, namely direct acting antivirals (DAA), has brought a new and highly successful approach to treatment of hepatitis C. Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population. Thus, an enhanced cascade of care, which should include the population under 18 years of age, can help achieve the WHO goal by focusing on elimination in the youngest populations. This review will present an overview of the natural history, clinical features, and management of HCV in children and adolescents.
Collapse
Affiliation(s)
- Michael Evan Rogers
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
| | - William F Balistreri
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
| |
Collapse
|
|
9
|
Coronary Stents and Metal Allergy. Contact Dermatitis 2021. [DOI: 10.1007/978-3-030-36335-2_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
|
|
10
|
Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper. J Pediatr Gastroenterol Nutr 2020; 71:407-417. [PMID: 32826718 DOI: 10.1097/mpg.0000000000002814] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In 1989, a collaboration between the Centers for Disease Control (CDC) and a California biotechnology company identified the hepatitis C virus (HCV, formerly known as non-A, non-B hepatitis virus) as the causative agent in the epidemic of silent posttransfusion hepatitis resulting in cirrhosis. We now know that, the HCV genome is a 9.6 kb positive, single-stranded RNA. A single open reading frame encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield 10 individual gene products, consisting of 3 structural proteins (core and envelope glycoproteins E1 and E2) and 7 nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which participate in posttranslational proteolytic processing and replication of HCV genetic material. Less than 25 years later, a new class of medications, known as direct-acting antivirals (DAAs) which target these proteins, were introduced to treat HCV infection. These highly effective antiviral agents are now approved for use in children as young as 3 years of age and have demonstrated sustained virologic responses exceeding 90% in most genotypes. Although tremendous scientific progress has been made, the incidence of acute HCV infections has increased by 4-fold since 2005, compounded in the last decade by a surge in opioid and intravenous drug use. Unfortunately, awareness of this deadly hepatotropic virus among members of the lay public remains limited. Patient education, advocacy, and counseling must, therefore, complement the availability of curative treatments against HCV infection if this virus is to be eradicated.
Collapse
|
|
11
|
Smith SK. Pediatric Hepatitis C. Adv Pediatr 2020; 67:47-56. [PMID: 32591063 DOI: 10.1016/j.yapd.2020.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Sara Kathryn Smith
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco, 550 16th Street, 5th Floor, Mail Code 0136, San Francisco, CA 94158, USA
| |
Collapse
|
|
12
|
Kim NG, Kullar R, Khalil H, Saab S. Meeting the WHO hepatitis C virus elimination goal: Review of treatment in paediatrics. J Viral Hepat 2020; 27:762-769. [PMID: 32386099 DOI: 10.1111/jvh.13317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/06/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.
Collapse
Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | | | - Haydar Khalil
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| |
Collapse
|
|
13
|
|
|
14
|
Saab S, Kullar R, Amini C, Gounder P. WITHDRAWN: The next frontier: universal hepatitis C virus screening in pregnant women. Am J Obstet Gynecol 2020:S0002-9378(20)30133-2. [PMID: 32044311 DOI: 10.1016/j.ajog.2020.01.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 11/04/2019] [Accepted: 01/30/2020] [Indexed: 12/09/2022]
Abstract
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Collapse
Affiliation(s)
- Sammy Saab
- Departments of Surgery, Medicine, and Nursing, University of California at Los Angeles, Los Angeles, CA
| | | | | | | |
Collapse
|
|
15
|
Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 510] [Impact Index Per Article: 102.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
| | | |
Collapse
|
|
16
|
Ragusa R, Corsaro LS, Frazzetto E, Bertino E, Bellia MA, Bertino G. Hepatitis C Virus Infection in Children and Pregnant Women: An Updated Review of the Literature on Screening and Treatments. AJP Rep 2020; 10:e121-e127. [PMID: 32257593 PMCID: PMC7108952 DOI: 10.1055/s-0040-1709185] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 02/20/2020] [Indexed: 12/14/2022] Open
Abstract
Objective The aim of the paper is to review the current information relating to the diagnosis and treatment of hepatitis C virus (HCV) infection in pregnant women and children, particularly those infected by mother-to-child transmission. Study Design A review of published literature was performed to identify relevant articles published between January 2015 and March 2019 on: HCV infection in pregnant woman, mother-to child-transmission of HCV and HCV infection in pediatrics. The results of the evaluation of the different studies were summarized in two sections describing separately the screening and effective treatments in pregnant women and children. Results The rate of mother-to-child transmission of HCV is approximately 5%. HCV infection is strongly associated with cholestasis and preterm birth. Prenatal diagnosis of hepatitis C virus has a dual benefit for mother and child. Perinatally infected children develop cirrhosis in earlier age than those who acquire HCV as adolescents. Pregnant women with cirrhosis have a higher risk of poor maternal and neonatal outcomes than those without cirrhosis. Conclusion To improve public health, universal screening of pregnant women for HCV infection should be performed. Early identification of women and children with HCV infection is important to enable them to be included in assessment and/or treatment programs.
Collapse
Affiliation(s)
- Rosalia Ragusa
- Health Technology Assessment Committee, Health Directorate, University Hospital “G. Rodolico,” Catania, Italy
| | - Liberato Simone Corsaro
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Evelise Frazzetto
- Hepatology Unit, A.O.U. Policlinico-Vittorio Emanuele, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Emanuele Bertino
- Department of Drug Sciences, University of Catania, Catania, Italy
| | | | - Gaetano Bertino
- Hepatology Unit, A.O.U. Policlinico-Vittorio Emanuele, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| |
Collapse
|
|
17
|
Coronary Stents and Metal Allergy. Contact Dermatitis 2020. [DOI: 10.1007/978-3-319-72451-5_81-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
|
18
|
Indolfi G, Easterbrook P, Dusheiko G, El-Sayed MH, Jonas MM, Thorne C, Bulterys M, Siberry G, Walsh N, Chang MH, Meyers T, Giaquinto C, Wirth S, Chan PL, Penazzato M. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4:477-487. [PMID: 30982721 DOI: 10.1016/s2468-1253(19)30046-9] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 01/20/2019] [Accepted: 01/22/2019] [Indexed: 02/06/2023]
Abstract
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. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1-19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1-3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12-17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas.
Collapse
Affiliation(s)
- Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Philippa Easterbrook
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland.
| | - Geoffrey Dusheiko
- King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Manal H El-Sayed
- Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Claire Thorne
- UCL Great Ormond Street Institute of Child Health, University College London, NIHR GOSH BRC, London, UK
| | - Marc Bulterys
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
| | - George Siberry
- Office of the US Global AIDS Coordinator, US Department of State, Washington, DC, USA
| | - Nick Walsh
- Pan American Health Organization, World Health Organization Regional Office for the Americas, Washington, DC, USA
| | - Mei-Hwei Chang
- Department of Paediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Tammy Meyers
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Carlo Giaquinto
- Department of Women and Child Health, University of Padova, Padova, Italy
| | - Stefan Wirth
- Department of Paediatrics, Helios Medical Centre Wuppertal, Witten-Herdecke University, Witten, Germany
| | - Po-Lin Chan
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Martina Penazzato
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
| |
Collapse
|
|
19
|
|
|
20
|
Squires JE, Balistreri WF. Hepatitis C virus infection in children and adolescents. Hepatol Commun 2017; 1:87-98. [PMID: 29404447 PMCID: PMC5721428 DOI: 10.1002/hep4.1028] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/17/2017] [Accepted: 02/22/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center Pittsburgh PA
| | - William F Balistreri
- Division of Gastroenterology Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati OH
| |
Collapse
|
|
21
|
Affiliation(s)
- Deirdre Kelly
- Liver Unit, Birmingham Children's Hospital, Birmingham, UK.
| |
Collapse
|