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Pokorska-Śpiewak M, Dobrzeniecka A, Talarek E, Aniszewska M, Pluta M, Marczyńska M, Indolfi G. Health-related Quality of Life in Children and Adolescents After Successful Treatment of Chronic Hepatitis C With Sofosbuvir/Velpatasvir: One-year Outcomes. Pediatr Infect Dis J 2025; 44:405-410. [PMID: 39774052 PMCID: PMC11980881 DOI: 10.1097/inf.0000000000004675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/27/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND AND AIMS The aim of this study was to assess the health-related quality of life (HRQL) of children with chronic hepatitis C (CHC) at 1 year after the effective treatment with sofosbuvir/velpatasvir (SOF/VEL). METHODS All 50 patients treated for CHC with a fixed dose SOF/VEL in the noncommercial, nonrandomized, open-label PANDAA-PED study achieved sustained virologic response at 12 weeks after the end of treatment. Evaluation of HRQL at 1-year posttreatment was compared with the baseline (before the treatment) assessment. KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting were used. The normal range for the population was set to T values of 40-60 points. Child-parent agreement was analyzed using the intraclass correlation coefficient (ICC). RESULTS Mean T values were within the normal range for all HRQL dimensions. A significant improvement in "autonomy & parent relation" in children's self-assessment (from 48.3 to 51.5, P = 0.03) was observed. In parent proxy assessment, a significant decrease occurred in "school" dimension (from 49.5 to 45.8, P = 0.03), which was not revealed at 3-month posttreatment. Older age was associated with worse HRQL scores in all dimensions. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor-to-moderate agreement for most single measures, lower than at 3-month posttreatment analysis. CONCLUSIONS This is the first study to present the long-term influence of treatment with direct-acting antivirals on patient-reported outcomes in children. At 1 year after effective treatment with SOF/VEL, an improvement in some areas of children's well-being was revealed, which may indicate also some patient-reported outcomes benefits of direct-acting antiviral therapy. Despite the improvement in the child self-report of "autonomy & parent relation," there was a more pronounced discrepancy between children self-reports and parents proxy reports in all dimensions of HRQL. Older patients' age correlated with worse HRQL assessment. If this finding is mediated by the duration of hepatitis C virus infection, it would support recommendation for the treatment of younger children.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Dobrzeniecka
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Ewa Talarek
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Małgorzata Aniszewska
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Pluta
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Marczyńska
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Giuseppe Indolfi
- Department of Neurofarba, Meyer Children’s University of Florence, Florence, Italy
- Meyer Children’s Hospital IRCCS, Florence, Italy
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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.
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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
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Goh L, Hardikar W. Hepatitis C in Children-An Asia-Pacific Concise Perspective. Pathogens 2024; 13:860. [PMID: 39452731 PMCID: PMC11510634 DOI: 10.3390/pathogens13100860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/25/2024] [Accepted: 09/25/2024] [Indexed: 10/26/2024] Open
Abstract
Since the discovery of hepatitis C virus (HCV) in 1989, we now have curative treatment options with direct-acting antiviral therapies. By increasing the rate of treatment and reducing transmission, the eradication of HCV is potentially achievable. Nonetheless, the feasibility and implementation of this goal remains challenging. This article sums up the approach to managing children with HCV in the Asia-Pacific region and lists some of the difficulties and complexities surrounding this issue.
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Affiliation(s)
- Lynette Goh
- Department of Gastroenterology, Hepatology and Nutrition, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
| | - Winita Hardikar
- Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne, Parkville, VIC 3052, Australia
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Samadder RK, Ray G, Dutta S, Hazra A, Sadhukhan P, Chowdhury A, Ray R, Ahammed SM. The Efficacy and Safety of Sofosbuvir and Daclatasvir Treatment in Children and Adolescents With Thalassemia and Hepatitis C Virus Infection. J Clin Exp Hepatol 2024; 14:101310. [PMID: 38264577 PMCID: PMC10801307 DOI: 10.1016/j.jceh.2023.101310] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 11/27/2023] [Indexed: 01/25/2024] Open
Abstract
Background/Aim Thalassemia patients are susceptible to hepatitis C virus (HCV) infection due to blood transfusions. Currently, data on treating HCV in thalassemic children with direct-acting antivirals is lacking. This study was performed to determine the efficacy and safety of sofosbuvir-daclatasvir combination therapy in thalassemic children and adolescents. Methods A nonrandomized, open-label, interventional study was carried out in a tertiary care hospital. Consecutive noncirrhotic treatment-naïve thalassemic patients with HCV infection with viremia, within the age group of 6-18 years, were treated with the combination of sofosbuvir-daclatasvir: 200 mg + 30 mg for age 6-11 years (Group A) and 400 mg + 60 mg for age 12-18 years (Group B). The primary endpoint was sustained virological response at 12 weeks (SVR12). Results A total of 70 patients (Group A 45, 64% male; Group B 25, 40% male) were recruited. The mean age was 8.5 years and 13.9 years in the two groups. Mean HCV Ribonucleic acid (RNA) levels in Groups A and B were 446906.1 IU/ml and 256187.8 IU/ml, respectively. SVR12 was achieved in 43 of 45 (95.5%) patients on an intention-to-treat basis and 43 of 44 (97.7%) patients on a perprotocol basis in Group A, and all patients in Group B (100%). In both groups, there was a significant improvement in biochemical parameters. Among the two patients who did not achieve SVR12 in Group A, one required termination of therapy due to urticaria. Conclusion Sofosbuvir-daclatasvir based treatment in noncirrhotic, treatment-naive thalassemic children and adolescents infected with HCV is effective and safe.
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Affiliation(s)
- Riten K. Samadder
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Gautam Ray
- Divisions of Pediatric Gastroenterology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Supradip Dutta
- Division of Virus Laboratory, ICMR-National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India
| | - Avijit Hazra
- Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Provash Sadhukhan
- Division of Virus Laboratory, ICMR-National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India
| | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Raja Ray
- Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Sk. Mahiuddin Ahammed
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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Indolfi G, Gonzalez-Peralta RP, Jonas MM, Sayed MHE, Fischler B, Sokal E, Wirth S, Nicastro E. ESPGHAN recommendations on treatment of chronic hepatitis C virus infection in adolescents and children including those living in resource-limited settings. J Pediatr Gastroenterol Nutr 2024; 78:957-972. [PMID: 38369891 DOI: 10.1002/jpn3.12160] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 08/29/2023] [Accepted: 10/25/2023] [Indexed: 02/20/2024]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV-related liver disease has advanced considerably thanks to development and improvements in therapy. Direct-acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype-specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age-specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource-limited settings.
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Affiliation(s)
- Giuseppe Indolfi
- Department NEUROFARBA University of Florence, Florence, Italy
- Paediatric and Liver Unit, Meyer Children's Hospital IRCCS, Firenze, Italy
| | - Regino P Gonzalez-Peralta
- Pediatric Gastroenterology, Hepatology and Liver Transplant, AdventHealth for Children, AdventHealth Transplant Institute, Orlando, Florida, USA
| | | | - Manal Hamdy-El Sayed
- Department of Paediatrics, Children's Hospital, Ain Shams University, Cairo, Egypt
| | - Björn Fischler
- Department of Paediatrics, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Etienne Sokal
- UCLouvain, Cliniques Universitaires St Luc, Pediatric Hepatology, Brussels, Belgium
| | - Stefan Wirth
- Department of Paediatrics, Helios University Hospital Wuppertal, Witten-Herdecke University, Germany
| | - Emanuele Nicastro
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
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Anton-Păduraru DT, Azoicăi AN, Trofin F, Murgu AM, Mîndru DE, Bocec AS, Halițchi COI, Zota GR, Păduraru D, Nastase EV. Diagnosis, Management, and Prognosis of Cystic Fibrosis-Related Liver Disease in Children. Diagnostics (Basel) 2024; 14:538. [PMID: 38473009 DOI: 10.3390/diagnostics14050538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 02/28/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease.
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Affiliation(s)
- Dana-Teodora Anton-Păduraru
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
- "Sf. Maria" Children Emergency Hospital, 700309 Iasi, Romania
| | - Alice Nicoleta Azoicăi
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
- "Sf. Maria" Children Emergency Hospital, 700309 Iasi, Romania
| | - Felicia Trofin
- Department of Preventive Medicine and Interdisciplinarity-Microbiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
| | - Alina Mariela Murgu
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
- "Sf. Maria" Children Emergency Hospital, 700309 Iasi, Romania
| | - Dana Elena Mîndru
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
- "Sf. Maria" Children Emergency Hospital, 700309 Iasi, Romania
| | - Ana Simona Bocec
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iaṣi, Romania
| | | | - Gabriela Rusu Zota
- Department of Pharmacology, Clinical Pharmacology and Algesiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Diana Păduraru
- "Dr. C. I. Parhon" Clinical Hospital, 700503 Iaṣi, Romania
| | - Eduard Vasile Nastase
- Department of Internal Medicine II-Infectious Diseases, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Clinical Hospital of Infectious Diseases "Sf. Parascheva", 700116 Iasi, Romania
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Indolfi G, Easterbrook P, Giometto S, Malik F, Chou R, Lucenteforte E. Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis. Liver Int 2024; 44:663-681. [PMID: 38293756 DOI: 10.1111/liv.15827] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 10/13/2023] [Accepted: 12/18/2023] [Indexed: 02/01/2024]
Abstract
BACKGROUND AND AIMS We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. METHODS We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. RESULTS A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). CONCLUSIONS All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO RECORD CRD42020146752.
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Affiliation(s)
- Giuseppe Indolfi
- Department Neurofarba, University of Florence, Florence, Italy
- Paediatric and Liver Unit, Meyer Children's Hospital IRCCS, Firenze, Italy
| | - Philippa Easterbrook
- Global HIV, Hepatitis and STI Programmes, World Health Organization Headquarters, Geneva, Switzerland
| | - Sabrina Giometto
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Farihah Malik
- Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Roger Chou
- Departments of Medicine, and Medical Informatics & Clinical Epidemiology, Oregon Health Sciences University, Portland, Oregon, USA
| | - Ersilia Lucenteforte
- Department of Statistics, Computer Science and Applications «G. Parenti», University of Florence, Florence, Italy
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AbdelMagid AM, Abbassi MM, Ebeid FS, Farid SF, El-Sayed MH. Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study. Clin Ther 2024; 46:e12-e22. [PMID: 37925363 DOI: 10.1016/j.clinthera.2023.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/08/2023] [Accepted: 10/09/2023] [Indexed: 11/06/2023]
Abstract
PURPOSE Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007. METHODS This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults. FINDINGS Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant. IMPLICATIONS Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed. CLINICALTRIALS gov identifier: NCT03903185.
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Affiliation(s)
- Aya M AbdelMagid
- Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Maggie M Abbassi
- Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Fatma S Ebeid
- Pediatric Hematology, Oncology and BMT Department, Ain Shams University, Cairo, Egypt; Faculty of Medicine, Ain Shams University Research Institute-Clinical Research Center (MASRI-CRC), Cairo, Egypt
| | - Samar F Farid
- Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Manal H El-Sayed
- Pediatric Hematology, Oncology and BMT Department, Ain Shams University, Cairo, Egypt; Faculty of Medicine, Ain Shams University Research Institute-Clinical Research Center (MASRI-CRC), Cairo, Egypt
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Pokorska-Śpiewak M, Talarek E, Aniszewska M, Pluta M, Dobrzeniecka A, Marczyńska M, Indolfi G. Health-related quality of life in patients aged 6-18 years with chronic hepatitis C treated with sofosbuvir/velpatasvir. Liver Int 2024; 44:93-102. [PMID: 37735963 DOI: 10.1111/liv.15744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/01/2023] [Accepted: 09/11/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health-related quality of life (HRQL) of children with chronic hepatitis C. METHODS In the non-commercial, non-randomized, open-label PANDAA-PED study, 50 children aged 6-18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child-parent agreement was analysed using the intra-class correlation coefficient (ICC) and Bland-Altman test. RESULTS Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well-being based on the children's self-assessment (from 48.53 to 51.21, p = .03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p = .06) was noticed. After the treatment, the proportion of children self-assessing their physical well-being as below normal significantly decreased from 17% to 5% (p = .007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland-Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). CONCLUSIONS A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well-being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Ewa Talarek
- Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Małgorzata Aniszewska
- Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Pluta
- Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Dobrzeniecka
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Marczyńska
- Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Giuseppe Indolfi
- Department of Neurofarba, Meyer Children's University of Florence, Florence, Italy
- Meyer Children's Hospital IRCCS, Florence, Italy
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10
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Drysdale K, Persson A, Smith AKJ, Wallace J, Valentine K, Gray RM, Bryant J, Hamilton M, Newman CE. Professional perspectives on serodiscordant family service provision in the context of blood-borne viruses. HEALTH SOCIOLOGY REVIEW : THE JOURNAL OF THE HEALTH SECTION OF THE AUSTRALIAN SOCIOLOGICAL ASSOCIATION 2023; 32:145-160. [PMID: 35980804 DOI: 10.1080/14461242.2022.2110922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/03/2022] [Indexed: 05/18/2023]
Abstract
In recognition of the broader relational aspects of viral infections, family support is considered important when someone is diagnosed with a blood-borne virus (BBV), such as HIV, hepatitis C (HCV) and hepatitis B (HBV). However, families' own support needs are often not a priority in service provision within the BBV sector. In this article, we draw on qualitative interviews with 20 key informants working in various professional capacities in health, social policy, care and advocacy sectors in Australia, and explore their experiences and perspectives on family inclusivity in their services. Overall, key informants acknowledged the diversity of what constitutes family, and consistently viewed family engagement as beneficial to both diagnosed individuals and the wider familial networks affected by a diagnosis. However, prioritising individual care in support services presented barriers to engaging families, which are further complicated by the role of stigma in shaping the social realities of living with a BBV. Increasing understanding in service provision settings that serodiscordance can be a family experience has the potential to widen this analytic lens to consider the support needs of families in their own right.
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Affiliation(s)
- Kerryn Drysdale
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
| | - Asha Persson
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
| | - Anthony K J Smith
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
| | | | - Kylie Valentine
- Social Policy Research Centre, UNSW Sydney, Sydney, Australia
| | - Rebecca M Gray
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
| | - Joanne Bryant
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
| | - Myra Hamilton
- Centre of Excellence in Population Ageing Research, Work and Organisational Studies, University of Sydney, Sydney, Australia
| | - Christy E Newman
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
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11
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Curtis MR, Chappell C. Evidence for Implementation: HIV/HCV Coinfection and Pregnancy. Curr HIV/AIDS Rep 2023; 20:1-8. [PMID: 36652107 PMCID: PMC9846668 DOI: 10.1007/s11904-022-00643-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2022] [Indexed: 01/19/2023]
Abstract
PURPOSE OF REVIEW In the context of the opioid epidemic, hepatitis C virus (HCV) infection prevalence is increasing among women of reproductive age. Pregnant people with HIV/HCV coinfection may be at increased risk of adverse pregnancy and neonatal outcomes, although research in this key population is lacking. RECENT FINDINGS Treatment with directly acting antivirals (DAAs) has transformed the clinical care for most patients with HCV. However, pregnant people were excluded from trials of these medications. A recent phase I study has shown promise with excellent safety profile for ledipasvir-sofosbuvir; demonstrating no episodes of perinatal transmission, 100% sustained virologic response, and no safety concerns. Pregnancy represents a time of maximal interaction with the healthcare system and therefore an ideal window of opportunity to cure HCV. Current observational data regarding pregnant people who are co-infected with HCV and HIV suggest poor outcomes such as increased risk of preterm birth; however, there are no prospective and well-controlled studies to fully understand the impact of HIV/HCV coinfection on pregnancy. Phase 1 studies suggest that DAAs are well-tolerated and effective during pregnancy. Only through large, prospective clinical trials will we be able to understand the interaction of HCV and HIV during pregnancy and to evaluate safety and efficacy of DAAs in this key population.
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Affiliation(s)
- Megan Rose Curtis
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
- Boston Medical Center, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
| | - Catherine Chappell
- Department of Obstetrics, Gynecology, and Reproductive sciences, University of Pittsburgh, PA, Pittsburgh, USA
- Magee-Women's Research Institute, Pittsburgh, PA, USA
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12
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Venkatesh V, Seetharaman K, Anushree N. Treatment of hepatitis C in children and adolescents: how far have we reached? World J Pediatr 2023; 19:107-119. [PMID: 36129634 DOI: 10.1007/s12519-022-00612-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 08/18/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. DATA SOURCES This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. RESULTS Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. CONCLUSION The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.
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Affiliation(s)
- Vybhav Venkatesh
- Department of Gastroenterology and Hepatobiliary Sciences, IMS and SUM Hospital, SOA University, Bhubaneswar, India
| | - Keerthivasan Seetharaman
- Department of Pediatrics, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
| | - Neha Anushree
- Department of Pediatrics, Command Hospital-Southern Command, Pune, 411040, India.
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13
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Foster MA, Moorman AC, Teshale EH. Hepatitis C Virus. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1156-1160.e3. [DOI: 10.1016/b978-0-323-75608-2.00220-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Fukuoka T, Bessho K, Hosono S, Abukawa D, Mizuochi T, Ito K, Murakami J, Tanaka H, Miyoshi Y, Takano T, Tajiri H. The impact of treatment on the psychological burden of mothers of children with chronic hepatitis C virus infection: a multicenter, questionnaire survey. Sci Rep 2022; 12:22116. [PMID: 36543833 PMCID: PMC9772351 DOI: 10.1038/s41598-022-25519-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022] Open
Abstract
Mothers of children with chronic hepatitis C virus (HCV) infection experience anxiety about the health of their children. In this study we assessed an impact of treating children with chronic HCV infection on the psychological burden of their mothers. This was a multicenter, questionnaire survey conducted at six institutions in Japan. A newly-developed questionnaire for this study was used to assess changes in the mothers' various concerns regarding HCV infection and thoughts about their child's HCV infection. Responses at the time of diagnosis and at the time of the survey were compared between mothers of children who had received treatment and those without treatment. Responses were received from 36 of 37 eligible mothers (11 and 25, non-treatment and treatment groups, respectively). All children in treatment group had successfully eliminated the virus. Mothers in both groups were psychologically stressed in various ways, including concern about their child's health in the present and future at the time of diagnosis, concern about school, employment, and marriage, concern about the behavior of others towards them and infecting others with HCV, and feelings of guilt regarding their child. These concerns were significantly lower in the present compared to at the time of diagnosis in treatment group, and the rate of decrease was significantly higher in treatment group compared to non-treatment group. Successful treatment greatly reduced mothers' concerns about their children's HCV infection, indicating that treatment during childhood is beneficial from the perspective of the mothers' psychological burden.
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Affiliation(s)
- Tomoya Fukuoka
- grid.136593.b0000 0004 0373 3971Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuhiko Bessho
- grid.136593.b0000 0004 0373 3971Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Satoyo Hosono
- grid.272242.30000 0001 2168 5385Division of Cancer Screening Assessment and Management, National Cancer Center Japan Institute for Cancer Control, Tokyo, Japan
| | - Daiki Abukawa
- grid.415988.90000 0004 0471 4457Division of General Pediatrics and Gastroenterology, Miyagi Children’s Hospital, Miyagi, Japan
| | - Tatsuki Mizuochi
- grid.410781.b0000 0001 0706 0776Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan
| | - Koichi Ito
- grid.260433.00000 0001 0728 1069Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Jun Murakami
- grid.265107.70000 0001 0663 5064Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Tottori, Japan
| | - Hideo Tanaka
- Osaka Prefecture Fujiidera Public Health Center, Osaka, Japan
| | - Yoko Miyoshi
- grid.136593.b0000 0004 0373 3971Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tomoko Takano
- grid.416985.70000 0004 0378 3952Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Hitoshi Tajiri
- grid.258622.90000 0004 1936 9967Department of Pediatrics, Faculty of Medicine Hospital, Kinki University, Osaka, Japan
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15
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Schwarzenberg SJ, Palermo JJ, Ye W, Huang S, Magee JC, Alazraki A, Jay Freeman A, Harned R, Karmazyn B, Karnsakul W, Leung DH, Ling SC, Masand P, Molleston JP, Murray KF, Navarro OM, Nicholas JL, Otto RK, Paranjape SM, Siegel MJ, Stoll J, Towbin AJ, Narkewicz MR, Alonso EM. Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children. J Pediatr Gastroenterol Nutr 2022; 75:635-642. [PMID: 36070552 PMCID: PMC9624376 DOI: 10.1097/mpg.0000000000003605] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. METHODS Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. RESULTS Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. CONCLUSIONS Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
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Affiliation(s)
- Sarah Jane Schwarzenberg
- Pediatric Gastroenterology, Hepatology and Nutrition, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN
| | - Joseph J. Palermo
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Wen Ye
- Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI
| | - Suiyuan Huang
- Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI
| | - John C. Magee
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI
| | - Adina Alazraki
- Department of Radiology, Emory University School of Medicine and Children’s Healthcare of Atlanta, Egleston, Atlanta, GA
| | - A. Jay Freeman
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Emory University School of Medicine, and Children’s Healthcare of Atlanta, Atlanta, GA
| | - Roger Harned
- Division of Pediatric Radiology, Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
| | - Boaz Karmazyn
- Pediatric Radiology, Riley Hospital for Children, Indianapolis, IN
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, John Hopkins School of Medicine, Baltimore, MD
| | - Daniel H. Leung
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Texas Children’s Hospital, Houston TX
| | - Simon C. Ling
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Canada
| | - Prakash Masand
- Division Radiology, Texas Children’s Hospital, Houston TX
| | - Jean P. Molleston
- Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN
| | - Karen F. Murray
- Pediatric Institute, Cleveland Clinic and Cleveland Clinic Children’s, Cleveland, OH
| | - Oscar M. Navarro
- Department of Medical Imaging, University of Toronto and Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jennifer L. Nicholas
- Division of Pediatric Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine
| | - Randolph K. Otto
- Department of Radiology, Seattle Children’s Hospital, Seattle, WA
| | - Shruti M. Paranjape
- Division of Pediatric Pulmonology, John Hopkins School of Medicine, Baltimore, MD
| | - Marilyn J. Siegel
- Division of Pediatric Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine
| | - Janis Stoll
- Division of Gastroenterology and Nutrition, Washington University School of Medicine, St Louis, MO
| | - Alexander J. Towbin
- Department of Radiology, Cincinnati Children’s Hospital Medical Center and Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Michael R. Narkewicz
- Digestive Health Institute, Children’s Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Estella M. Alonso
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL
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16
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AbouBakr O, Ezz El Regal M, Sarhan AA, El Sayed Zaki M, Noaman A. Safety and Efficacy of Ledipasvir/Sofosbuvir in the Treatment of Chronic Hepatitis C Virus Infection in Treatment-Naïve Children without and with Comorbidities. Paediatr Drugs 2022; 24:529-537. [PMID: 35838919 PMCID: PMC9439969 DOI: 10.1007/s40272-022-00522-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/19/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection represents a crucial health problem in children that greatly influences their quality of life. Many efforts have been directed toward investing in effective drugs with a high safety profile and oral administration for better compliance. OBJECTIVES This study aims to assess the safety of a fixed-dose combination of ledipasvir/sofosbuvir plus drug efficacy and sustained virologic response (SVR) at 12 weeks after treatment discontinuation. METHOD One tablet (90 mg ledipasvir, 400 mg sofosbuvir) was administered to treatment-naïve children aged 12-18 years weighing at least 35 kg with chronic HCV infection for 6 months, genotype 4. Patients were divided into 2 groups, (1) without comorbidities (24 patients) and (2) with comorbidities (26 patients). RESULTS At the end of the therapy, all patients (100%) had SVR and a significant reduction of liver enzymes with mild tolerable side effects. CONCLUSION Ledipasvir/sofosbuvir fixed-dose combination is a safe and highly effective therapeutic option in Egyptian children aged ≥ 12 years, with chronic HCV infection, genotype 4, either without or with comorbidities.
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Affiliation(s)
- Othman AbouBakr
- Pediatrics Department, Pediatric Gastroenterology, and Hepatology Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt
| | - Mohammed Ezz El Regal
- Pediatrics Department, Pediatric Gastroenterology, and Hepatology Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt
| | - Amr Ali Sarhan
- Pediatrics Department, Pediatric Nephrology, and Dialysis Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt
| | - Maysaa El Sayed Zaki
- Clinical Pathology Department, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt
| | - Ahmed Noaman
- Pediatrics Department, Pediatric Critical Care Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura University, Mansoura, Egypt
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17
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Sato K, Yamazaki Y, Kanayama Y, Uehara D, Tojima H, Suga T, Kakizaki S, Sohara N, Horiguchi N, Uraoka T. Adolescents with chronic hepatitis C might be good candidates for direct-acting antiviral therapy. Clin Case Rep 2022; 10:e05690. [PMID: 35414915 PMCID: PMC8980949 DOI: 10.1002/ccr3.5690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 03/18/2022] [Indexed: 11/08/2022] Open
Abstract
Three Japanese adolescents with chronic hepatitis C were treated by direct-acting antivirals (DAAs). No adverse events or laboratory abnormalities were observed during and after DAA therapy, and a sustained virological response was achieved in all cases. The emotional functioning of the patients and their mothers were improved after DAA therapy.
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Affiliation(s)
- Ken Sato
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
- Department of HepatologyHeisei Hidaka ClinicGunmaJapan
| | - Yuichi Yamazaki
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Yuki Kanayama
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Daisuke Uehara
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Hiroki Tojima
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Takayoshi Suga
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Satoru Kakizaki
- Department of GastroenterologyNational Hospital Organization Takasaki General Medical CenterGunmaJapan
| | | | - Norio Horiguchi
- Department of General MedicineGunma University Graduate School of MedicineGunmaJapan
| | - Toshio Uraoka
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
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18
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Malik F, Chulanov V, Pimenov N, Fomicheva A, Lundin R, Levina N, Thorne C, Turkova A, Indolfi G. Treatment and monitoring of children and adolescents with hepatitis C in Russia: Results from a multi-centre survey on policy and practice. J Virus Erad 2022; 8:100063. [PMID: 35198235 PMCID: PMC8844707 DOI: 10.1016/j.jve.2022.100063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/10/2022] [Accepted: 02/01/2022] [Indexed: 11/17/2022] Open
Abstract
Background The Russian Federation has the largest paediatric hepatitis C virus (HCV) disease burden in the World Health Organization European region with an estimated 118,000 children living with HCV viraemia. Direct-acting antivirals (DAAs) have been available for adults in Russia since 2015 and approved for treatment of adolescents aged ≥12 years since 2019. We evaluated DAA availability and uptake for HCV treatment of children and adolescents and clinical practices on diagnosis and management of paediatric HCV in Russia. Methods A survey was distributed to regional ministries of health in 85 administrative regions during September 2020. The survey consisted of 22 items collecting data on: type of facility, aggregate patient characteristics, HCV testing practices for children and pregnant women and HCV management and treatment practices for children. Results Survey responses were received from 37 of the 85 regions in Russia (response rate 44%). 2159 children and adolescents with chronic HCV were in follow-up; 1089 (50%) were female. Of 2080 children with available data on age-groups, 134 (6%) were <3 years, 336 (16%) 3-<6 years, 718 (35%) 6-<12 years and 892 (43%) 12-<18 years. 134 (15%) of 892 adolescents ≥12 years received DAAs, 96 (72%) glecaprevir/pibrentasvir, 26 (19%) sofosbuvir, 8 (6%) daclatasvir and 4 (3%) sofosbuvir/ledipasvir. Conclusions This study provides a baseline of DAA uptake in early stages of rollout for children and adolescents. The use of DAAs for treatment of adolescents in Russia presents a unique opportunity for HCV micro-elimination in this population.
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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: 1] [Impact Index Per Article: 0.3] [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.
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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
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20
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Prevalence, Genotypic Distribution and the associated Risk Factors of Hepatitis C Infection in Pakistan Pediatric Patients. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.1.01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Hepatitis C virus (HCV) is an important contributor to chronic morbidity and mortality in developing countries. The study’s objective was to determine the genotype distribution and risk factors associated with the transmission of HCV infections in pediatric patients. Rapid screening and confirmation by the enzyme-linked immunosorbent assay (ELISA) were used to analyze 585 pediatric blood specimens hospitalized and visited the outpatient department of the largest tertiary care hospital in Pakistan. Detection and genotyping of HCV RNA were performed using a real-time polymerase chain reaction (RT-PCR). Demographic data and a history of risk factors were gathered through a survey questionnaire. HCV RNA was detected in 323 (72.4%) cases which showed viral load ranging from Log10 IU/mL < 3 to > 6 IU/mL. HCV genotype 3a was detected in 256 (79.3%) cases while type 3b and 1a was observed in 36 (11.1%) and 31 (9.6%) patients, respectively. HCV positivity was significantly associated with the cases from rural areas [p = 0.005; odds ratio (OR) 1.65; 95% CI 1.16-2.23] and also significantly associated with low-income group [p < 0.001; OR 5.75; 95% CI 3.90-8.40]. The primary risk factors associated with HCV transmission in children were family history (p = 0.002), blood transfusion (p = 0.03), surgical procedures (p = 0.02), and history of injections (p = 0.05). HCV genotype 3a is the most common genotype in children. The main risk factors for HCV transmission in children are blood transfusion, surgical procedures, and injection practices by informal health care providers.
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21
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Wirth S. Chronic Viral Hepatitis B and C. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:833-842. [DOI: 10.1007/978-3-030-80068-0_63] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Rubino C, Trapani S, Indolfi G. Sofosbuvir/velpatasvir for the treatment of hepatitis C in pediatric patients. Expert Rev Gastroenterol Hepatol 2021; 15:1097-1105. [PMID: 34338120 DOI: 10.1080/17474124.2021.1963231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Introduction: 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.Areas covered: A literature search of PUBMED and EMBASE was conducted on April 30th and updated on June 10th. Other citations were identified in references of available literature and from ClinicalTrials.gov. The aim of the present research was to outline and discuss the pharmacokinetics, clinical efficacy, tolerability and safety of sofosbuvir/velpatasvir, exploring its actual and potential use in children and adolescents with chronic hepatitis C virus infection.Expert opinion: Five combinations of direct-acting antivirals, of whom three with pangenotypic activity, are now approved for children. No major differences in efficacy and safety profile have been described. Limited access to treatment still is a major issue, especially in low and middle-income countries.
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Affiliation(s)
- Chiara Rubino
- Pediatric And Liver Unit, Meyer Children's University Hospital Of Florence, Florence, Italy
| | - Sandra Trapani
- Department Of Health Sciences, University Of Florence And Meyer Children's University Hospital Of Florence, Florence, Italy
| | - Giuseppe Indolfi
- Pediatric And Liver Unit, Meyer Children's University Hospital Of Florence, Florence, Italy.,Neurofarba Department, University Of Florence, Florence, Italy
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23
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Santos JC, Saquetto MB, Gomes Neto M, Santos JDLD, Silva LR. NEUROPSYCHOMOTOR DEVELOPMENT IN CHILDREN AND ADOLESCENTS WITH LIVER DISEASES: SYSTEMATIC REVIEW WITH META-ANALYSIS. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:217-226. [PMID: 34231665 DOI: 10.1590/s0004-2803.202100000-40] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 12/07/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND The nature of liver disease, the evolutionary course and duration of liver diseases, as well as the degree of severity and disability can trigger multiple outcomes with repercussions on neuromotor acquisition and development. OBJECTIVE To systematically review and conduct a meta-analysis to evaluate the effects of liver disease on the neuropsychomotor development of children and adolescents with their native livers and those who underwent liver transplantation. METHODS Observational studies published since the early 1980s until June 2019 were sought in the PubMed and Scopus databases. An α value of 0.05 was considered significant. The statistical heterogeneity of the treatment effect between the studies was assessed by the Cochran's Q test and the I2 inconsistency test, in which values above 25 and 50% were considered indicative of moderate and high heterogeneity, respectively. Analyses were performed with Review Manager 5.3. RESULTS Twenty-five studies met the eligibility criteria, including 909 children and adolescents with liver disease. Meta-analyses showed deficits in total IQ -0.41 (95%CI: -0.51 to -0.32; N: 9,973), verbal IQ -0.38 (95%CI: -0.57 to -0.18; N: 10,284) and receptive language -0.85 (95%CI: -1.16 to -0.53; N: 921) in liver transplantation, and those with native livers who had symptoms early had total and verbal IQ scores (85±8.8; 86.3±10.6 respectively) lower than the scores of those with late manifestations (99.5±13.8; 96.2±9.2). Gross motor skill was reduced -46.29 (95%CI: -81.55 to -11.03; N: 3,746). CONCLUSION Acute or chronic liver disease can cause declines in cognitive, motor and language functions. Although the scores improve after liver transplantation, children remain below average when compared to healthy children.
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Affiliation(s)
- Juliana Costa Santos
- Universidade Federal da Bahia (UFBA), Salvador, BA, Brasil.,Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, BA, Brasil
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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.
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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
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Mari PC, Gulati R, Fragassi P. Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2021; 12:45-53. [PMID: 33994820 PMCID: PMC8112853 DOI: 10.2147/ahmt.s263864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 04/21/2021] [Indexed: 12/09/2022]
Abstract
The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.
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Affiliation(s)
- Paula Chaves Mari
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Reema Gulati
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Philip Fragassi
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
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Malik F, Bailey H, Chan P, Collins IJ, Mozalevskis A, Thorne C, Easterbrook P. Where are the children in national hepatitis C policies? A global review of national strategic plans and guidelines. JHEP Rep 2021; 3:100227. [PMID: 33665586 PMCID: PMC7898178 DOI: 10.1016/j.jhepr.2021.100227] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS It is estimated that 3.26 million children and adolescents worldwide have chronic HCV infection. To date, the global response has focused on the adult population, but direct-acting antiviral (DAA) regimens are now approved for children aged ≥3 years. This global review describes the current status of policies on HCV testing and treatment in children, adolescents, and pregnant women in WHO Member States. METHODS We identified national strategic plans and/or clinical practice guidelines (CPGs) for HCV infection from a World Health Organization (WHO) database of national policies from Member States as of August 2019. A standardised proforma was used to abstract data on polices or recommendations on testing and treatment in children, adolescents and pregnant women. Analysis was stratified according to the country-income status and results were validated through WHO regional focal points through August 2020. RESULTS National HCV policies were available for 122 of the 194 WHO Member States. Of these, the majority (n = 71/122, 58%) contained no policy recommendations for either testing or treatment in children or adolescents. Of the 51 countries with policies, 24 had specific policies for both testing and treatment, and were mainly from the European region; 18 countries for HCV testing only (12 from high- or upper-middle income); and 9 countries for treatment only (7 high- or upper-middle income). Twenty-one countries provided specific treatment recommendations: 13 recommended DAA-based regimens for adolescents ≥12 years and 6 still recommended interferon/ribavirin-based regimens. CONCLUSIONS There are significant gaps in policies for HCV-infected children and adolescents. Updated guidance on testing and treatment with newly approved DAA regimens for younger age groups is needed, especially in most affected countries. LAY SUMMARY To date, the predominant focus of the global response towards elimination of hepatitis C has been on the testing and treatment of adults. Much less attention has been paid to testing and treatment among children and adolescents, although in 2018 an estimated 3.26 million were infected with HCV. Our review shows that many countries have no national guidance on HCV testing and treatment in children and adolescents. It highlights the urgent need for advocacy and updated policies and guidelines specific for children and adolescents.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- APASL, Asian Pacific Association for the Study of the Liver
- Adolescents
- CPGs, clinical practice guidelines
- Children
- Clinical practice guidelines
- DAAs, direct-acting antivirals
- EASL, European Association for the Study of the Liver
- ESPGHAN, European Society for Paediatric Gastroenterology Hepatology and Nutrition
- GHSS, Global Health Sector Strategy
- GLE, glecaprevir
- GT, genotype
- Hepatitis C
- IDU, injecting drug use
- IFN, interferon
- LED, ledipasvir
- LMICs, low- and middle-income countries
- MoH, ministries of health
- NASPGHAN, North American Society for Pediatric Gastroenterology Hepatology and Nutrition
- NSPs, national strategic plans
- National strategic plans
- PIB, pibrentasvir
- Policies
- Policy review
- Pregnancy
- RBV, ribavirin
- SOF, sofosbuvir
- VEL, velpatasvir
- WHO, World Health Organization
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Affiliation(s)
- Farihah Malik
- UCL Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Heather Bailey
- UCL Institute for Global Health, University College London, London, UK
| | - Polin Chan
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Intira Jeannie Collins
- Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | | | - Claire Thorne
- UCL Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Philippa Easterbrook
- Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland
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Treatment of Chronic Hepatitis C in Young Children Reduces Adverse Outcomes and Is Cost-Effective Compared with Deferring Treatment to Adulthood. J Pediatr 2021; 230:38-45.e2. [PMID: 32890583 DOI: 10.1016/j.jpeds.2020.08.088] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/31/2020] [Accepted: 08/28/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the cost-effectiveness of treating young children with chronic hepatitis C virus (HCV) with new direct-acting antivirals. STUDY DESIGN A state-transition model of chronic HCV was developed to conduct a cost-effectiveness analysis comparing treatment at age 6 years vs delaying treatment until age 18 years. Model inputs were derived from recently conducted systematic reviews, published literature, and government statistics. Medical care costs were obtained from linked population level laboratory and administrative data (Ontario, Canada). Outcomes are expressed in expected quality-adjusted life-years and costs (CAD$). Analysis included a base-case to estimate the expected value and one-way and probabilistic sensitivity analyses to evaluate the impact of uncertainty of the model inputs. RESULTS After 20 years, treating 10 000 children early would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths. The incremental cost-effectiveness ratio of early treatment compared to delayed treatment was approximately $12 690/quality-adjusted life-years gained and considered cost-effective. Model results were robust to variation in fibrosis progression rates, disease state-based costs, treatment costs, and utilities. CONCLUSIONS Delaying treatment until age 18 years results in an increased lifetime risk of late-stage liver complications. Early treatment in children is cost effective. Our work supports clinical and health policies that broaden HCV treatment access to young children.
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Rodriguez-Baez N. Hepatitis C in Young Children: To Treat or Not to Treat - Is It Cost-Effective? J Pediatr 2021; 230:9-10. [PMID: 33075370 DOI: 10.1016/j.jpeds.2020.10.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 10/14/2020] [Indexed: 02/07/2023]
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Pearce ME, Yu A, Alvarez M, Bartlett SR, Binka M, Jeong D, Clementi E, Adu P, Wilton J, Yoshida EM, Pick N, Buxton JA, Wong J, Jassem A, Krajden M, Janjua NZ. Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019. PLoS One 2020; 15:e0244575. [PMID: 33382774 PMCID: PMC7775094 DOI: 10.1371/journal.pone.0244575] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 12/11/2020] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE Current guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women. METHODS BC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses. RESULTS In 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019. CONCLUSION Prenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.
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Affiliation(s)
- Margo E. Pearce
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
- * E-mail:
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Sofia R. Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Emilia Clementi
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Prince Adu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - James Wilton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Eric M. Yoshida
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
- Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Neora Pick
- Department of Medicine, Division of Infectious Diseases, University of British Columbia Vancouver, British Columbia, Canada
- British Columbia Women’s Hospital, Vancouver, British Columbia, Canada
| | - Jane A. Buxton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Agatha Jassem
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z. Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
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Using Preventive Health Alerts in the Electronic Health Record Improves Hepatitis C Virus Testing Among Infants Perinatally Exposed to Hepatitis C. Pediatr Infect Dis J 2020; 39:920-924. [PMID: 32453202 DOI: 10.1097/inf.0000000000002757] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Perinatal exposure to hepatitis C virus (HCV) is a major public health issue, and poor testing rates leave many children with infection unidentified. We sought to use the electronic health record (EHR) to promote guideline-directed HCV testing among infants born to mothers with HCV infection in an urban, safety-net hospital system. METHODS Our study population was identified using our EHR database, Epic. Children were included in the study if they had perinatal HCV exposure, were 18 months to 18 years of age and had at least 1 encounter in a primary or urgent care clinic during the study period. Our study included retrospective (October 2011 to February 2015) and prospective (February 2015 to May 2018) arms. Our EHR-based intervention was initiated in the prospective arm and recommended a one-time HCV antibody test at or after the age of 18 months using a health maintenance reminder. The health maintenance reminder activated a point-of-care alert and a linked HCV testing order set in all prespecified encounters during the intervention period. RESULTS Median time to appropriate HCV testing decreased from 96.2 months preintervention to 9.1 months postintervention (P < 0.0001), and rate of completed antibody testing increased from 14% to 61% (P < 0.0001). CONCLUSIONS Among children with perinatal HCV exposure, using a point-of-care alert within the EHR significantly increased the HCV antibody testing rate in accordance with American Academy of Pediatrics (AAP) recommendations. More effective EHR-based interventions combined with increased provider awareness of appropriate HCV testing in perinatally exposed infants is imperative.
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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.
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El-Sayed MH, Indolfi G. Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination. Semin Liver Dis 2020; 40:213-224. [PMID: 32526785 DOI: 10.1055/s-0040-1708812] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be addressed as part of a national policy for elimination in the whole population, namely macroelimination, or could be fragmented into a microelimination approach targeting the high-risk population groups. Children born to HCV-infected mothers, adolescents who are injecting drugs, migrants, and those suffering from inherited blood diseases are important target populations. After the U.S. Food and Drug Administration approval for the use of DAAs in children aged 3 years and above, evidence from clinical trials and real-world experience was accumulated using brand and generic medicines, with sustained virological response rates exceeding 95%. The evidence created should guide policies on the management of hepatitis C in children and adolescents. There are many challenges in managing HCV in this left-behind marginalized population. The lack of awareness and epidemiological data, consent age, prohibitive prices of medicines, and absence of policies on access to diagnostics, treatment, and linkage to care are among the many barriers to service delivery that should be addressed to achieve the elimination goal by 2030.
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Affiliation(s)
- Manal H El-Sayed
- Department of Pediatrics, Faculty of Medicine, Clinical Research Center, Ain Shams University, Cairo, Egypt
| | - Giuseppe Indolfi
- Pediatric and Liver Unit, Meyer Children's University Hospital and Department NEUROFARBA, University of Florence, Florence, Italy
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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.
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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
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Chappell CA, Scarsi KK, Kirby BJ, Suri V, Gaggar A, Bogen DL, Macio IS, Meyn LA, Bunge KE, Krans EE, Hillier SL. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. LANCET MICROBE 2020; 1:e200-e208. [PMID: 32939459 PMCID: PMC7491553 DOI: 10.1016/s2666-5247(20)30062-8] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Hepatitis C virus (HCV) infection is increasing among pregnant women because of the opioid epidemic, yet there are no interventions to reduce perinatal HCV transmission or to treat HCV during pregnancy. Physiological changes in pregnancy alter the pharmacokinetics of some medications; thus, our aim was to compare the pharmacokinetic parameters of ledipasvir 90 mg plus sofosbuvir 400 mg during pregnancy with non-pregnant women. Methods This was an open-label, phase 1 study of pregnant women with genotype 1 HCV infection and their infants. A reference group of women who had participated in pharmacokinetic studies of ledipasvir–sofosbuvir during phase 2 and 3 trials was used. Participants were enrolled at Magee-Womens Hospital (Pittsburgh, PA, USA) between 23 and 24 weeks’ gestation and had a 12-week course of oral ledipasvir–sofosbuvir (daily 90 mg ledipasvir plus 400 mg sofosbuvir). Three 12-h intensive pharmacokinetic visits were done at 25–26, 29–30, and 33–34 weeks’ gestation and individual pharmacokinetics were summarised by geometric mean across the three visits. The primary outcome, analysed in all participants without suspected dosing errors, was the ledipasvir–sofosbuvir area under the concentration–time curve of the dosing interval (AUCtau) during pregnancy compared with the reference group by geometric mean ratio. This study is registered with ClinicalTrials.gov, NCT02683005. Findings From Oct 1, 2016, to Sept 30, 2018, 29 pregnant women were screened and nine (31%) were enrolled. Eight (89%) women were included in the primary analysis. Ledipasvir and sofosbuvir exposures were similar in the pregnant women versus the non-pregnant reference group (geometric mean ratio of AUCtau ledipasvir 89·3% [90% CI 68·7–116·1]; sofosbuvir 91·1% [78·0–106·3]). Interpretation Ledipasvir–sofosbuvir was safe and effective without clinically meaningful differences in drug exposure among pregnant versus non-pregnant women. Funding National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health/Office of Research on Women’s Health, and Gilead Sciences.
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Affiliation(s)
- Catherine A Chappell
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
| | - Kimberly K Scarsi
- College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA
| | | | | | | | - Debra L Bogen
- Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Leslie A Meyn
- Magee-Womens Research Institute, Pittsburgh, PA, USA
| | - Katherine E Bunge
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
| | - Elizabeth E Krans
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
| | - Sharon L Hillier
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA
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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: 513] [Impact Index Per Article: 102.6] [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
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36
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Rosenthal P, Schwarz KB, Gonzalez‐Peralta RP, Lin C, Kelly DA, Nightingale S, Balistreri WF, Bansal S, Jonas MM, Massetto B, Brainard DM, Hsueh C, Shao J, Parhy B, Davison S, Feiterna‐Sperling C, Gillis LA, Indolfi G, Sokal EM, Murray KF, Wirth S. Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection. Hepatology 2020; 71:31-43. [PMID: 31222783 PMCID: PMC7004103 DOI: 10.1002/hep.30821] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 06/14/2019] [Indexed: 12/11/2022]
Abstract
Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty-four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%-100%). The patient who did not achieve SVR12 was a 4-year-old who discontinued treatment after 3 days because of "abnormal drug taste." The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3-year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.
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Affiliation(s)
| | | | | | | | | | - Scott Nightingale
- University of Newcastle and John Hunter Children’s HospitalAustralia
| | | | | | | | | | | | | | | | | | | | | | | | | | - Etienne M. Sokal
- Cliniques Universitaires St. Luc, Université Catholique de LouvainBrusselsBelgium
| | - Karen F. Murray
- University of Washington School of Medicine and Seattle Children’s HospitalSeattleWA
| | - Stefan Wirth
- Helios Medical CenterWitten/Herdecke UniversityWuppertalGermany
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37
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Greenaway E, Biondi MJ, Feld JJ, Ling SC. Hepatitis C virus infection in mothers and children. CANADIAN LIVER JOURNAL 2019; 2:210-224. [DOI: 10.3138/canlivj.2019-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 03/28/2019] [Indexed: 12/22/2022]
Abstract
Many unique challenges are associated with hepatitis C infection in mothers and children. The preconception, antenatal, and postnatal phases each offer opportunities to reduce transmission of the virus from mother to infant or to identify the need for treatment. Management of children and youth with hepatitis C is now entering the era of direct-acting antivirals. Improvements are needed in the identification of infected mothers and children and their linkage to appropriate expert care.
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Affiliation(s)
- Emma Greenaway
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Mia J Biondi
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Arthur Labatt Family School of Nursing, Western University, London, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Simon C Ling
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
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38
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Freriksen JJM, van Seyen M, Judd A, Gibb DM, Collins IJ, Greupink R, Russel FGM, Drenth JPH, Colbers A, Burger DM. Review article: direct-acting antivirals for the treatment of HCV during pregnancy and lactation - implications for maternal dosing, foetal exposure, and safety for mother and child. Aliment Pharmacol Ther 2019; 50:738-750. [PMID: 31448450 PMCID: PMC6773363 DOI: 10.1111/apt.15476] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 07/25/2019] [Accepted: 08/02/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct-acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. AIM To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation METHODS: A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. RESULTS Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy-induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. CONCLUSIONS Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.
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Affiliation(s)
- Jolien J M Freriksen
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.,Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Minou van Seyen
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ali Judd
- MRC Clinical Trials Unit at University College London, London, UK
| | - Diana M Gibb
- MRC Clinical Trials Unit at University College London, London, UK
| | - Intira J Collins
- MRC Clinical Trials Unit at University College London, London, UK
| | - Rick Greupink
- Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Frans G M Russel
- Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Angela Colbers
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - David M Burger
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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Karnsakul W, Schwarz KB. Management of Hepatitis C Infection in children in the era of Direct-acting Antiviral Agents. J Viral Hepat 2019; 26:1034-1039. [PMID: 30980688 DOI: 10.1111/jvh.13113] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/22/2019] [Accepted: 03/26/2019] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis C certainly is a global health burden in children as well as in adults. Spontaneous viral clearance can occur in early childhood but is uncommon thereafter. Although the majority of cases are asymptomatic during childhood and young adulthood, without an effective treatment, children who acquire HCV via vertical transmission can develop chronic liver disease and other complications including end-stage liver disease and hepatocellular carcinoma in adulthood. Efforts from worldwide health organizations, the pharmaceutical industry, and clinical and research institutions have resulted in very effective interferon-free therapy with direct-acting antiviral agents (DAAs) for HCV-infected children. In this manuscript, we will briefly review the epidemiology of HCV in children, historic treatment, current published data on DAAs in children and conclude with suggestions for management of the child with HCV in the era of DAAs.
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Affiliation(s)
- Wikrom Karnsakul
- Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kathleen B Schwarz
- Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland
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40
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El-Shabrawi M, Hassanin F. Paediatric hepatitis C virus infection and its treatment: Present, past, and future. Arab J Gastroenterol 2019; 20:163-174. [PMID: 31585703 DOI: 10.1016/j.ajg.2019.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/01/2019] [Accepted: 09/15/2019] [Indexed: 01/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the world. It is a challenging medico-social problem in the paediatric population. High HCV infection rates are reported in low and middle incomes countries. From the health economic point of view treatment of hepatitis C virus (HCV) with subsequent virus eradication is very effective as it eliminates the long-term sequelae of untreated or maltreated HCV. In this review we summarize the updates and highlight the historical approach of treatment of chronic HCV infection in children in the new era of directly acting antiviral (DAA) agents.
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41
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Amirsardari Z, Rahmani F, Rezaei N. Cognitive impairments in HCV infection: From pathogenesis to neuroimaging. J Clin Exp Neuropsychol 2019; 41:987-1000. [PMID: 31405320 DOI: 10.1080/13803395.2019.1652728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
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Affiliation(s)
- Zahra Amirsardari
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Farzaneh Rahmani
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran
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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.
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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
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Cost Effectiveness of Early Treatment with Direct-Acting Antiviral Therapy in Adolescent Patients with Hepatitis C Virus Infection. J Pediatr 2019; 207:90-96. [PMID: 30738661 DOI: 10.1016/j.jpeds.2018.12.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 11/12/2018] [Accepted: 12/05/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the cost effectiveness of early treatment with direct-acting antiviral therapy in adolescent patients with chronic hepatitis C virus (HCV) infection compared with treatment deferral. STUDY DESIGN We constructed a Markov model to assess the cost effectiveness of treating a hypothetical cohort of 30 000 adolescent patients with chronic HCV at age 12 years compared with deferring treatment until adulthood from a societal perspective. Model inputs for transition probabilities, HCV treatment and medical care costs, and quality-adjusted life-year (QALY) utilities were derived from the literature and wholesale acquisition estimates. Deterministic sensitivity analyses varied parameters for non-HCV medical care and treatment cost, reinfection rates, treatment uptake, disease progression, liver transplant survival, and treatment with recently approved pangenotypic direct-acting antiviral agents. Discounted costs and total QALYs per person were quantified after 30 years. Cost effectiveness was evaluated as the incremental change in total medical costs per QALY gained. RESULTS The incremental cost effectiveness of early treatment initiation compared with deferred treatment was approximately $27 000 per QALY gained after 30 years and considered cost effective. In a scenario analysis, hypothetical treatment initiation with currently available pangenotypic agents would be even more cost effective, ranging from $10 000 to $21 000 per QALY gained. Cost-effectiveness estimates were sensitive to variations in decompensated cirrhosis progression in adolescence, adult reinfection, and treatment uptake in adults. CONCLUSIONS Early treatment in adolescent patients with chronic HCV infection with currently available direct-acting antivirals seems to be cost effective compared with deferred treatment. Future efforts to control the HCV epidemic should include increasing the number of children treated.
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Modin L, Arshad A, Wilkes B, Benselin J, Lloyd C, Irving WL, Kelly DA. Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol 2019; 70:371-378. [PMID: 30496763 DOI: 10.1016/j.jhep.2018.11.013] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 10/16/2018] [Accepted: 11/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis C virus (HCV) infection is a global health burden. Although HCV infection rarely contributes to morbidity during childhood, most HCV-infected children develop chronic HCV with a lifetime risk of liver disease. Little is known about the development of long-term liver disease and the effect of treatment in patients infected with HCV in childhood. METHOD This study was a retrospective review of patients infected with HCV in childhood enrolled in HCV Research UK. A total of 1,049 patients were identified and included. RESULTS The main routes of infection were intravenous drug use (53%), blood product exposure (24%) and perinatal infection (11%). Liver disease developed in 32% of patients, a median of 33 years after infection, irrespective of the mode of infection. Therefore, patients with perinatal exposure developed cirrhosis at an earlier age than the rest of the risk groups. The incidence of hepatocellular carcinoma (HCC) was 5%, liver transplant 4% and death occurred in 3%. Overall, 663 patients were treated (55% with interferon/pegylated interferon and 40% with direct-acting antivirals). Sustained virological response (SVR) was achieved in 406 (75%). There was a higher mortality rate among patients without SVR vs. those with SVR (5% vs. 1%, p = 0.003). Treatment was more effective in patients without cirrhosis and disease progression was less frequent (13%) than in patients with cirrhosis at the time of therapy (28%) p < 0.001. Patients with cirrhosis were more likely to develop HCC, require liver transplantation, or die. CONCLUSION HCV infection in young people causes significant liver disease, which can now be prevented with antiviral therapy. Early treatment, especially before development of cirrhosis is essential. Detection of HCV should be aimed at relevant risk groups and antiviral therapy should be made available in childhood to prevent long-term liver disease and spread of HCV. LAY SUMMARY Chronic hepatitis C virus (HCV) infection is a global health problem, which can now be treated with potent direct-acting antiviral drugs. This study demonstrates that HCV infection in childhood causes serious liver disease in 32% of patients, a median of 33 years after infection, irrespective of age, mode and route of infection. Disease outcomes were better in patients treated before the development of advanced liver disease. Antiviral therapy should be made available in childhood to prevent long-term liver disease and the spread of HCV.
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Affiliation(s)
- Line Modin
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK.
| | - Adam Arshad
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
| | - Bryony Wilkes
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Jennifer Benselin
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Carla Lloyd
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
| | - William L Irving
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Deirdre A Kelly
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
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Direct-acting antiviral Therapy Is Safe and Effective in Pediatric Chronic Hepatitis C: The Public Health Perspective. J Pediatr Gastroenterol Nutr 2019; 68:74-80. [PMID: 30211847 DOI: 10.1097/mpg.0000000000002139] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES We assessed the efficacy of decentralized public health services and safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for prevention and control of CHC in Punjab, India. METHODS Consecutive children with CHC [age ≥12 to <18 years; both treatment-naïve (TN) and treatment-experienced (TE)] were enrolled. Genotyping was not recommended for non-cirrhotic patients and were treated with sofosbuvir (SOF)+ daclatasvir (DCV) for 12 weeks, while genotyping was recommended for patients with cirrhosis. Patients with cirrhosis and genotype (G2) were treated with SOF+DCV+ribavirin (RBV) for 12 weeks, G3 with SOF+DCV+RBV for 24 weeks and G1, 4, 5, and 6 patients were treated with SOF+ledipasvir (LDV)+RBV for 12 weeks. Treatment duration was increased to 24 weeks if RBV was not tolerated. RESULTS In the first 16 months (June 18, 2016-October 31, 2017), 88 children (mean age 15.8 years; 69.3.3% boys, 72.3% rural) were enrolled. The mean baseline hepatitis C virus RNA log10 IU/mL was 6.0 (range 4.2-7.5 log10 IU/mL), 65.5% with G3, and 2 (2.5%) with cirrhosis. Of 57 with completed treatment, sustained virological response (SVR) 12 was achieved in 56 (98.2%). Unsafe medical practices (55.5%), IV drug abuse (11.1%), and prior surgery (2.7%) were risk-factors for transmission (n = 36). Comparable results were noted in G3 (SVR at 12 weeks [SVR12], 94.3%) versus non-G3 (SVR12, 100%; P = 0.073). No serious adverse effects like anemia and decompensation were reported. CONCLUSIONS The study demonstrates that the decentralized algorithm-based public-health program can ensure high efficacy (SVR12, 98.2%) and low-cost DAA-based treatment of pediatric patients with CHC.
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Kushner T, Terrault NA. Hepatitis C in Pregnancy: A Unique Opportunity to Improve the Hepatitis C Cascade of Care. Hepatol Commun 2019; 3:20-28. [PMID: 30619991 PMCID: PMC6312659 DOI: 10.1002/hep4.1282] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 10/19/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C has increasingly affected women of child-bearing age over the past few years as a result of the opioid epidemic. In this review, we discuss the effect of hepatitis C on pregnancy outcomes, effect of pregnancy on hepatitis C, as well as implications on management of hepatitis C during pregnancy.
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Affiliation(s)
- Tatyana Kushner
- Division of Liver DiseasesIcahn School of Medicine at Mount SinaiNew YorkNY
| | - Norah A. Terrault
- Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCA
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Murray KF, Balistreri WF, Bansal S, Whitworth S, Evans HM, Gonzalez-Peralta RP, Wen J, Massetto B, Kersey K, Shao J, Garrison KL, Parhy B, Brainard DM, Arnon R, Gillis LA, Jonas MM, Lin CH, Narkewicz MR, Schwarz K, Rosenthal P. Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. Hepatology 2018; 68:2158-2166. [PMID: 30070726 DOI: 10.1002/hep.30123] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/29/2018] [Indexed: 02/06/2023]
Abstract
Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)-infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir-sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg-sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.
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Affiliation(s)
- Karen F Murray
- University of Washington and Seattle Children's Hospital, Seattle, WA
| | | | | | | | - Helen M Evans
- Auckland Clinical Studies and Starship Child Health, Auckland, New Zealand
| | | | - Jessica Wen
- The Children's Hospital of Philadelphia, Philadelphia, PA
| | | | | | | | | | | | | | | | | | | | | | - Michael R Narkewicz
- University of Colorado, School of Medicine and Children's Hospital of Colorado, Aurora, CO
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Nwaohiri A, Schillie S, Bulterys M, Kourtis AP. Hepatitis C virus infection in children: How do we prevent it and how do we treat it? Expert Rev Anti Infect Ther 2018; 16:689-694. [PMID: 30091654 DOI: 10.1080/14787210.2018.1509707] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important contributor to the worldwide burden of liver-related morbidity and mortality. Mother-to-child transmission of HCV ranges from 6 to 11% in different populations globally, but accurate estimates on the burden of pediatric HCV infection are limited because screening approaches are not consistent. Areas covered: The advent of new direct-acting antiviral agents that achieve very high rates of sustained virologic response (representing virologic cure) with short (i.e. 8-12 weeks) regimens has revolutionized the field of HCV treatment and led to the development of global elimination goals for HCV transmission and mortality. However, information on their safety during pregnancy and efficacy in preventing mother-to-child transmission is lacking. Currently, there are no approved treatment regimens with these antiviral agents for children younger than 12 years of age. Expert commentary: If these agents are shown to be safe during pregnancy and effective in preventing transmission to the infant, screening of pregnant women and antenatal treatment of those infected, could pave the way for eliminating pediatric HCV infection- particularly as these drugs become less costly and more accessible. Treatment of infected children when indicated, along with universal safe health care practices, can further pediatric HCV elimination.
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Affiliation(s)
- Anuli Nwaohiri
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Sarah Schillie
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Marc Bulterys
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Athena P Kourtis
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
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Abstract
OBJECTIVE The aim of the study was to determine the neurodevelopmental outcomes of children with liver diseases based on a systematical review of the literature. METHOD A literature search according to the PRISMA statement was conducted using predefined search terms in PubMed, Cochrane Library, and PsycINFO. The inclusion criterion was studies published from 2000 onwards that reported on the neurodevelopmental outcomes of term-born children with liver diseases. A narrative synthesis was done to appraise the studies. RESULTS Twenty-five studies were included (1913 children), 19 of which described children after liver transplantation (LTx; 1372 children). Sixty-seven percentage of the studies on children with liver diseases who survived with their native livers showed low-average or abnormal scores on specific subscales of cognitive and behavioral measures. In studies on children after LTx, this was 82%. After LTx, 83% of studies demonstrated impaired outcomes on behavior, whereas 42% of children received special education. Motor development was impaired in 82% of studies in children with native liver and after LTx. LIMITATIONS Studies were heterogenic because of sample sizes, etiology of liver disease and type of assessment tools used. CONCLUSIONS More than two-third of included studies showed neurodevelopmental deficits in children with liver diseases, affecting all neurodevelopmental areas. Knowledge on risk factors for impaired neurodevelopment is limited and lack of long-term follow-up is worrying, especially considering the increasing survival rates, resulting in more at-risk patients. Studying early predictors and risk factors of abnormal developmental trajectories of children with liver diseases is indicated to assess strategies to improve their long-term neurodevelopmental outcomes.
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Yang CHT, Goel A, Ahmed A. Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2018; 9:103-110. [PMID: 30104913 PMCID: PMC6071628 DOI: 10.2147/ahmt.s147896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.
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Affiliation(s)
- Christine Hong Ting Yang
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,
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