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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] [Download PDF] [Figures] [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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Nikolaeva L, Leybman E, Samokhvalov E, Kyuregyan K, Kichatova V, Isaeva O, Kuprianov V. Hepatitis C virus-specific markers in pediatric patients with chronic hepatitis C. Minerva Pediatr (Torino) 2025; 77:54-61. [PMID: 34859647 DOI: 10.23736/s2724-5276.21.06564-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The study aimed to investigate hepatitis C virus (HCV) specific markers in chronically infected children. The main objective was to explore the patterns of marker variability. METHODS HCV RNA, core antigen, anti-HCV IgM, and antibodies to individual viral proteins were detected using commercially available assays or experimental ELISA. RNA genotyping and recombination were performed by sequencing. RESULTS HCV RNA and core antigen were detected in serum samples of all children (N.=100). Anti-HCV IgM, anti-NS4AB IgG, and anti-NS5A IgG were revealed less often than antibodies to core and NS3 proteins. To elucidate the cause of this finding, all subjects were divided into 4 groups differing in hepatitis duration. It was anti-NS4AB only whose detection depended on the infection duration. A trend was established that the longer the hepatitis duration, the more frequently anti-HCV IgM was observed. No significant impact of HCV RNA load and NS4A/NS4B amino acid substitutions on anti-NS4AB IgG detection was found. The increase HCV genotype 3 was observed among children infected after 2000. The earliest case of infection caused by HCV intergenotype recombinant RF1_2k/1b was identified in a child vertically infected in 1997. CONCLUSIONS HCV genotypes and subtypes were found to be variable virus specific markers in children infected in 1997-2015. Over the period, there has been a trend to change the dominant HCV subtype and appearance of recombinant RF1_2k/1b in children. Among humoral markers, anti-NS4AB revealing is depended on chronic hepatitis C duration, while for anti-HCV IgM, only a trend was established. The detection of anti-NS4AB can be helpful in assessing the duration of chronic hepatitis C.
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Affiliation(s)
- Lyudmila Nikolaeva
- Department of Molecular Virology, Ivanovsky Institute of Virology, Gamaleya National Research Centre of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia -
| | - Elena Leybman
- Department of Molecular Virology, Ivanovsky Institute of Virology, Gamaleya National Research Centre of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
- Department of Children's Infectious Diseases, Pirogov Russian National Research Medical University, Ministry of Health, Moscow, Russia
| | - Evgeniy Samokhvalov
- Department of Molecular Virology, Ivanovsky Institute of Virology, Gamaleya National Research Centre of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | - Karen Kyuregyan
- Department of Virology, Russian Medical Academy of Continuing Professional Education, Ministry of Health, Moscow, Russia
| | - Vera Kichatova
- Department of Virology, Russian Medical Academy of Continuing Professional Education, Ministry of Health, Moscow, Russia
| | - Olga Isaeva
- Department of Virology, Russian Medical Academy of Continuing Professional Education, Ministry of Health, Moscow, Russia
| | - Victor Kuprianov
- Department of Molecular Biology of Microorganisms, Skryabin Institute of Bioengineering, Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Moscow, Russia
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Kerkar N, Hartjes K. Hepatitis C Virus-Pediatric and Adult Perspectives in the Current Decade. Pathogens 2024; 14:11. [PMID: 39860972 PMCID: PMC11769290 DOI: 10.3390/pathogens14010011] [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: 11/02/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age. However, treatment in the pediatric population has its own set of challenges. The World Health Organization (WHO) has made a pledge to eliminate HCV as a public health threat by 2030. Despite this, HCV continues to remain a global health burden, leading to cirrhosis as well as hepatocellular carcinoma, and is a reason for liver transplantation in the adult population. Although rare, these complications can also affect the pediatric population. A variety of new technologies t have become available in the current era and can advance our understanding of HCV are discussed. Artificial intelligence, machine learning, liver organoids, and liver-on-chip are some examples of techniques that have the potential to contribute to our understanding of the disease and treatment process in HCV. Despite efforts over several decades, a successful vaccine against HCV has yet to be developed. This would be an important tool to help in worldwide efforts to eliminate the virus.
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Affiliation(s)
- Nanda Kerkar
- Massachusetts General Brigham for Children, 175 Cambridge Street, Boston, MA 02114, USA;
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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] [Download PDF] [Figures] [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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Musto F, Stracuzzi M, Crivellaro E, Rubinacci V, Cibarelli A, Porro C, Ghidoni E, Zuccotti GV, Giacomet V. Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy. Pediatr Infect Dis J 2024; 43:813-818. [PMID: 38753999 PMCID: PMC11319081 DOI: 10.1097/inf.0000000000004374] [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] [Accepted: 05/23/2024] [Indexed: 05/18/2024]
Abstract
Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.
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Affiliation(s)
- Francesca Musto
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Marta Stracuzzi
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Elisa Crivellaro
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Valeria Rubinacci
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Alessandro Cibarelli
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Cecilia Porro
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Elena Ghidoni
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Gian Vincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital
- Department of Biosciences, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy
| | - Vania Giacomet
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
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Quek JWE, Loo JH, Lim EQ, Chung AHL, Othman ABB, Tan JJR, Barnett S, Nguyen MH, Wong YJ. Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis. EClinicalMedicine 2024; 74:102727. [PMID: 39109190 PMCID: PMC11301193 DOI: 10.1016/j.eclinm.2024.102727] [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: 02/18/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. METHODS We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. FINDINGS From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2 = 100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2 = 79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2 = 10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. INTERPRETATION HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. FUNDING None.
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Affiliation(s)
- Joo Wei Ethan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jing Hong Loo
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
| | | | | | | | - Jarell Jie-Rae Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Scott Barnett
- Division of Gastroenterology & Hepatology, Stanford University Medical Centre, Palo Alto, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology & Hepatology, Stanford University Medical Centre, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA
| | - Yu Jun Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore
- Duke-NUS Medical School, Singapore
- Division of Gastroenterology & Hepatology, University of Alberta, Edmonton, Canada
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Forna L, Bozomitu L, Lupu VV, Lupu A, Trandafir LM, Adam Raileanu A, Cojocariu C, Anton C, Girleanu I, Muzica CM. Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges. J Clin Med 2024; 13:4275. [PMID: 39064318 PMCID: PMC11278264 DOI: 10.3390/jcm13144275] [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: 04/28/2024] [Revised: 07/01/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
Background: Liver cirrhosis presents significant challenges in the pediatric population due to a complex interplay of etiological factors, clinical manifestations, and limited therapeutic options. The leading contributors to cirrhosis among pediatric patients are chronic cholestasis, metabolic disorders present from birth, and long-term hepatitis. Materials and method: Our narrative review aimed to synthesize literature data on the etiology, clinical picture, diagnostic techniques, optimal management of complications, and timely transplantation. Results: The epidemiology of liver cirrhosis in pediatric patients is evolving. The introduction of a universal vaccination and effective long-term viral suppression in viral hepatitis have significantly decreased complications rates. Liver transplantation programs worldwide have also improved the management of cirrhosis complications. Conclusions: Early diagnosis, comprehensive management strategies, and advancements in treatment modalities are critical for improving outcomes. Understanding these differences is crucial in providing age-appropriate care and support for those affected by cirrhosis.
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Affiliation(s)
- Lorenza Forna
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Laura Bozomitu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Vasile Valeriu Lupu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Ancuta Lupu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Laura Mihaela Trandafir
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Anca Adam Raileanu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, 700309 Iași, Romania; (L.F.); (V.V.L.); (A.L.); (L.M.T.); (A.A.R.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
| | - Camelia Cojocariu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Carmen Anton
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Irina Girleanu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cristina Maria Muzica
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iași, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, 700111 Iași, Romania
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Hartley C, Van T, Karnsakul W. Direct-Acting Antiviral Agents in Prevention of Maternal-Fetal Transmission of Hepatitis C Virus in Pregnancy. Pathogens 2024; 13:508. [PMID: 38921805 PMCID: PMC11206561 DOI: 10.3390/pathogens13060508] [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: 01/04/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication.
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Affiliation(s)
- Christopher Hartley
- The Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA
| | - Trung Van
- Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Jonas MM, Romero R, Rosenthal P, Lin CH, Verucchi G, Wen J, Balistreri WF, Whitworth S, Bansal S, Leung DH, Narkewicz MR, Gonzalez-Peralta RP, Mangia A, Karnsakul W, Rao GS, Shao J, de Jong J, Parhy B, Osinusi A, Kersey K, Murray KF, Sokal EM, Schwarz KB. Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection. J Pediatr Gastroenterol Nutr 2024; 78:1342-1354. [PMID: 38644678 DOI: 10.1002/jpn3.12045] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 02/20/2023] [Accepted: 03/13/2023] [Indexed: 04/23/2024]
Abstract
BACKGROUND The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. FINDINGS Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. INTERPRETATION The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.
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Affiliation(s)
| | - Rene Romero
- Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, USA
| | - Philip Rosenthal
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of California San Francisco, Benioff Children's Hospital, San Francisco, California, USA
| | - Chuan-Hao Lin
- Children's Hospital Los Angeles, Los Angeles, California, USA
| | | | - Jessica Wen
- University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | | | | | | | - Daniel H Leung
- Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Michael R Narkewicz
- School of Medicine and Children's Hospital of Colorado, University of Colorado, Aurora, Colorado, USA
| | | | - Alessandra Mangia
- Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Wikrom Karnsakul
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Girish S Rao
- Riley Hospital for Children, Indiana University School of Medicine, Indiana, Indianapolis, USA
| | - Jiang Shao
- Gilead Sciences Inc., Foster City, California, USA
| | - Jan de Jong
- Gilead Sciences Inc., Foster City, California, USA
| | | | - Anu Osinusi
- Gilead Sciences Inc., Foster City, California, USA
| | | | - Karen F Murray
- Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA
| | - Etienne M Sokal
- Cliniques Universitaires Saint-Luc, Service de Gastroentérologie Hépatologie Pédiatrique, Université Catholique de Louvain, Bruxelles, Belgique
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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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11
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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: 11] [Impact Index Per Article: 11.0] [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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12
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Jarasvaraparn C, Hartley C, Karnsakul W. Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children. Pathogens 2024; 13:180. [PMID: 38392918 PMCID: PMC10891648 DOI: 10.3390/pathogens13020180] [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: 12/15/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46201, USA
| | - Christopher Hartley
- Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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13
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Brigham D, Narkewicz MR. Profile of Sofosbuvir and Velpatasvir Combination in the Treatment of Chronic Hepatitis C in Children and Adolescents: Current Evidence. Ther Clin Risk Manag 2024; 20:1-7. [PMID: 38230373 PMCID: PMC10789568 DOI: 10.2147/tcrm.s326099] [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: 08/15/2023] [Accepted: 12/28/2023] [Indexed: 01/18/2024] Open
Abstract
Chronic hepatitis C (HCV) affects up to 3.25 million children and adolescents. Early treatment of HCV in children and adolescents reduces progression to advanced liver disease and cancer. Treatment for HCV has evolved to highly effective direct acting antiviral therapy in adults and now in children ≥3 years of age. This review focuses on the role of sofosbuvir and velpatasvir (SOF/VEL), a newer treatment of children and adolescents with chronic HCV. SOF/VEL is a pangenotypic DAA with primary clearance via the liver and biliary excretion. It has been studied in children and adolescents and is approved in the US for use in children and adolescents ≥3 years of age. Although the data are currently limited, SOF/VEL has demonstrated sustained viral response rates similar to comparable DAAs in the range of 95-98%. To date, side effects have been minimal.
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Affiliation(s)
- Dania Brigham
- Digestive Health Institute, Pediatric Liver Center, Children’s Hospital Colorado and University of Colorado School of Medicine, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, CO, USA
| | - Michael R Narkewicz
- Digestive Health Institute, Pediatric Liver Center, Children’s Hospital Colorado and University of Colorado School of Medicine, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, CO, USA
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14
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Ozdogan E, Arikan C. Liver fibrosis in children: a comprehensive review of mechanisms, diagnosis, and therapy. Clin Exp Pediatr 2023; 66:110-124. [PMID: 36550776 PMCID: PMC9989719 DOI: 10.3345/cep.2022.00367] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 09/14/2022] [Indexed: 12/23/2022] Open
Abstract
Chronic liver disease incidence is increasing among children worldwide due to a multitude of epidemiological changes. Most of these chronic insults to the pediatric liver progress to fibrosis and cirrhosis to different degrees. Liver and immune physiology differs significantly in children from adults. Because most of pediatric liver diseases have no definitive therapy, a better understanding of population and disease-specific fibrogenesis is mandatory. Furthermore, fibrosis development has prognostic significance and often guide treatment. Evaluation of liver fibrosis continues to rely on the gold-standard liver biopsy. However, many high-quality studies put forward the high diagnostic accuracy of numerous diagnostic modalities in this setting. Herein, we summarize and discuss the recent literature on fibrogenesis with an emphasis on pediatric physiology along with a detailed outline of disease-specific signatures, noninvasive diagnostic modalities, and the potential for antifibrotic therapies.
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Affiliation(s)
- Elif Ozdogan
- Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - Cigdem Arikan
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Koc University School of Medicine, Istanbul, Turkey
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15
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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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16
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HBV and HCV Infection in Children and Adolescents. Vaccines (Basel) 2023; 11:vaccines11020330. [PMID: 36851208 PMCID: PMC9962909 DOI: 10.3390/vaccines11020330] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/31/2023] [Indexed: 02/04/2023] Open
Abstract
Hepatitis B (HBV) and C (HCV) infections are the major causes of chronic liver disease and are associated with significant morbidity and mortality [...].
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17
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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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18
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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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19
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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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20
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Rădoi CL, Berbecaru EIA, Istrate-Ofițeru AM, Nagy RD, Drăgușin RC, Căpitănescu RG, Zorilă MV, Zorilă LG, Iliescu DG. Intrauterine Transmission of Hepatitis C Virus Concomitant with Isolated Severe Fetal Ascites. Pathogens 2022; 11:pathogens11111335. [PMID: 36422587 PMCID: PMC9697820 DOI: 10.3390/pathogens11111335] [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: 10/03/2022] [Revised: 11/10/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Perinatal Hepatitis C Virus (HCV) transmission occurs in 4–7% of the cases with detectable viremia at delivery. HCV testing in pregnancy is recommended. The fetal infection was previously described as asymptomatic although there are two cases, including this one, to report the presence of isolated fetal ascites in HCV infected fetuses. Case report: A 42-year-old patient, 3G, 3P, presented in the Emergency Room for painful uterine contraction. The third-trimester ultrasound examination noted severe fetal ascites, accompanied by hyperechoic bowels and polyhydramnios. The diagnosis required a detailed ultrasound exam, invasive testing (amniocentesis, cordocentesis, and fetal paracentesis), and a complete workup. The mother tested positive for HCV antibodies, and the fetal cord blood tested positive for HCV RNA. The ascites resolved after paracentesis, and the gastrointestinal and respiratory functions markedly improved. The fetus was delivered at term in good condition. Conclusions: The etiology of isolated fetal ascites is broad. This case may indicate that intrauterine HCV transmission is a potential cause of isolated fetal ascites in the absence of other explanation, and isolated fetal ascites can be the only sign revealed on a routine examination. We suspected, having no other detected cause for ascites, the intrauterine transmission of HCV. Invasive procedures, such as paracentesis, are required for abdominal decompression to manage isolated fetal ascites, as it may be a saving procedure. A genetic investigation is needed, and a good neonatal outcome is expected in the absence of fetal structural or genetic abnormalities, as in our case.
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Affiliation(s)
- Cristiana Luiza Rădoi
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Elena-Iuliana-Anamaria Berbecaru
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Correspondence: (E.-I.-A.B.); (A.-M.I.-O.)
| | - Anca-Maria Istrate-Ofițeru
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Department of Histology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Research Centre for Microscopic Morphology and Immunology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Correspondence: (E.-I.-A.B.); (A.-M.I.-O.)
| | - Rodica Daniela Nagy
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
| | - Roxana Cristina Drăgușin
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Razvan Grigoraș Căpitănescu
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marian Valentin Zorilă
- Department of Forensic Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lucian George Zorilă
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dominic Gabriel Iliescu
- Department of Obstetrics and Gynecology, Emergency Clinical County Hospital, 200642 Craiova, Romania
- Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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21
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Honegger JR, Gowda C. Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children. Curr Opin Infect Dis 2022; 35:468-476. [PMID: 35852787 PMCID: PMC9474609 DOI: 10.1097/qco.0000000000000856] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE OF REVIEW Direct-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies. RECENT FINDINGS In 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study. SUMMARY Paediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.
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Affiliation(s)
- Jonathan R. Honegger
- Division of Pediatric Infectious Diseases, Nationwide Children’s Hospital, Columbus, Ohio, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
- Center for Vaccines and Immunity, Abigail Wexner Research Institute, Columbus, Ohio, USA
| | - Charitha Gowda
- Division of Pediatric Infectious Diseases, Nationwide Children’s Hospital, Columbus, Ohio, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
- Partners For Kids, Nationwide Children’s Hospital, Columbus, Ohio, USA
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22
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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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23
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Stinco M, Bartolini E, Veronese P, Rubino C, Moriondo M, Ricci S, Trapani S, Azzari C, Resti M, Indolfi G. Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study. J Pediatr Gastroenterol Nutr 2022; 75:e2-e7. [PMID: 35653496 DOI: 10.1097/mpg.0000000000003481] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To prospectively describe the epidemiology and long-term outcome of childhood-acquired hepatitis C virus (HCV) infection in a large cohort of children followed at a single center. METHODS All children with chronic HCV infection followed at the Liver Unit of our tertiary Hospital in Florence (Italy) from January 1, 1988, to September 30, 2021, were included in the analysis. RESULTS The final sample consisted of 163 children (median age at enrollment 4 years, interquartile range (IQR): 10; median age at last follow-up 14 years, IQR: 7). The median duration of follow-up was 86 months (IQR: 112). One hundred twenty-five children were vertically infected and 26 acquired the infection horizontally. Twenty-six of the 125 children who were vertically infected (20.8%) underwent spontaneous clearance of HCV RNA at a median age of 4 years (IQR: 2), whereas all the others remained persistently viremic. One patient was diagnosed with cirrhosis; 2 presented clinically detectable extrahepatic manifestations (chronic urticaria). Thirty-two children (19.6%) received antiviral therapy: 8 out of 32 (25%) were treated with pegylated-interferon alfa-2b [sustained virological response (SVR) 24 weeks after the end of treatment in 7/8]; 24 out of 32 (75%) were treated with direct-acting antivirals (SVR 12 weeks after the end of treatment in 23/24). CONCLUSIONS The present study describes the largest cohort of children with chronic HCV infection prospectively evaluated with a long follow-up at a single center. HCV infection in children is often a chronic infection that can be cured with modern antiviral therapy. Early treatment could prevent the development of advanced liver disease.
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Affiliation(s)
- Mariangela Stinco
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Elisa Bartolini
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Piero Veronese
- the Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Chiara Rubino
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Maria Moriondo
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
| | - Silvia Ricci
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
- the Department of Health Sciences, Pediatric Section, University of Florence
| | - Sandra Trapani
- the Department of Health Sciences, Pediatric Section, University of Florence
| | - Chiara Azzari
- the Immunology Laboratory, Meyer Children's University Hospital, Florence, Italy
| | - Massimo Resti
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Giuseppe Indolfi
- From the Liver Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy
- the Department NEUROFARBA, University of Florence
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24
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Abstract
Hepatitis B and hepatitis C are a global burden and underscore the impact of preventable acute and chronic diseases on personal as well as population level health. Caring for pediatric patients with hepatitis B and C requires a deep understanding of the pathophysiology of viral processes. Insight into the epidemiology, transmission, and surveillance of these infections is critical to prevention and therapy. Extensive research in recent years has created a growing number of treatments, changing the landscape of the medical field's approach to the viral hepatitis pandemic.
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25
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Indolfi G, Kelly D, Nebbia G, Iorio R, Mania A, Giacomet V, Szenborn L, Shao J, Sang Yue M, Hsueh CH, Parhy B, Kersey K, Mangia A, Pawlowska M, Bansal S. Sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years old with HCV infection. Hepatology 2022; 76:445-455. [PMID: 35112372 DOI: 10.1002/hep.32393] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 12/21/2021] [Accepted: 12/27/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic HCV infection. In the USA and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults who previously received an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8-week or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype. METHODS In this Phase 2, multicenter study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients. RESULTS All patients (n = 21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21 of 21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults. CONCLUSIONS The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.
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Affiliation(s)
- Guiseppe Indolfi
- Department NEUROFARBA, Meyer Children's University Hospital, University of Florence, Florence, Italy
| | - Deirdre Kelly
- Birmingham Women's and Children's Hospital, University of Birmingham, Birmingham, UK
| | - Gabriella Nebbia
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Anna Mania
- Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | | | | | - Jiang Shao
- Gilead Sciences, Inc, Foster City, California, USA
| | - Mun Sang Yue
- Gilead Sciences, Inc, Foster City, California, USA
| | | | | | | | - Alessandra Mangia
- Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Malgorzata Pawlowska
- Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Toruń, Toruń, Poland
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26
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Mangone G, Serranti D, Bartolini E, Vigna V, Mastrangelo G, Ricci S, Trapani S, Azzari C, Resti M, Indolfi G. SNPs of the IFNL favour spontaneous clearance of HCV infection in children. Pediatr Res 2022; 91:1516-1521. [PMID: 33966053 DOI: 10.1038/s41390-021-01557-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 03/08/2021] [Accepted: 03/19/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Both spontaneous and treatment-induced clearance of hepatitis C virus (HCV) in adults have been associated with genetic polymorphisms in the interferon-λ genes. The aim of the present study was to confirm the association between the rs12979860 and evaluate the association between the rs368234815 and the rs4803217 single-nucleotide polymorphisms (SNPs) of the interferon-λ genes and the outcome of the infection in children. METHODS Alleles and genotypes frequencies of 32 children, who presented spontaneous clearance of the virus and 135 children, with viral persistence were compared with ethnically matched controls obtained from the 1000 Genomes Project and the International HapMap Project databases. RESULTS The frequencies of the C/C genotype of rs12979860, the TT/TT of the rs368234815 and the A/C of the rs4803217 were higher in the clearance group than in children with viral persistence (C/C versus T/T + C/T odds ratio (OR): 2.6; 90% confidence intervals (CI): 1.3-5; p = 0.01; TT/TT versus ΔG/TT + ΔG/ΔG OR: 2.8; 90% CI: 1.4-5.5; p = 0.01; and A/A versus A/C OR: 8.3; 90% CI: 1.5-45.9; p = 0.017, respectively) and with the ethnically matched controls. CONCLUSIONS The rs12979860, the rs368234815 and the rs4803217 SNPs are associated with spontaneous clearance of HCV in children. IMPACT Innate immune system response has a key role in the outcome of vertically acquired HCV infection in children. The rs12979860, the rs368234815 and the rs4803217 SNPs are associated with spontaneous clearance of HCV in children. Interferons-λ activate the Janus kinase-Stat pathway, which in turn induces several interferon-stimulated genes, leading to suppression of HCV replication both in vivo and in vitro.
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Affiliation(s)
- Giusi Mangone
- Immunology Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Daniele Serranti
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Elisa Bartolini
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Veronica Vigna
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Greta Mastrangelo
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy.,Department NEUROFARBA, University of Florence, Firenze, Italy
| | - Silvia Ricci
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Sandra Trapani
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy.,Department of Health Sciences, University of Florence, Firenze, Italy
| | - Chiara Azzari
- Immunology Unit, Meyer Children's University Hospital of Florence, Firenze, Italy.,Department of Health Sciences, University of Florence, Firenze, Italy
| | - Massimo Resti
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy. .,Department NEUROFARBA, University of Florence, Firenze, Italy.
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27
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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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28
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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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29
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Tajiri H, Bessho K, Nakayama Y, Abukawa D, Iitsuka Y, Ito Y, Inui A, Etani Y, Suzuki M, Takano T, Tanaka A, Mizuochi T, Miyoshi Y, Murakami J. Clinical practice guidelines for the management of children with mother-to-child transmitted hepatitis C virus infection. Pediatr Int 2022; 64:e14962. [PMID: 35224815 DOI: 10.1111/ped.14962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 08/10/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The first guidelines for care of pregnant women carrying the hepatitis C virus (HCV) and their infants were published in 2005 in Japan. Since then, evidence has gradually accumulated worldwide regarding the natural course and treatment of this condition and, especially in recent years, treatment for chronic hepatitis C in adult patients has made great progress. However, the clinical practice policy for children has not been standardized, and new clinical practice guidelines for children with mother-to-child (MTC) transmitted HCV infection have become necessary. METHODS In the development of the current guideline, we requested cooperation from The Japanese Society for Pediatric Infectious Diseases, The Japan Society of Hepatology, and the Japan Society of Obstetrics and Gynecology. The committee members were recommended and approved by each society to participate in developing the guidelines. The guideline was also created in accordance with the Minds Guide for Practice Guideline Development. The statements were prepared by consensus-building using the Delphi method, based on the comprehensively searched academic papers and guidelines. These articles were retrieved through searching the PubMed, Cochrane Library, and the Igaku Chuo Zasshi databases. RESULTS Eight clinical questions (CQs) with clinical statements were developed regarding etiology (CQs 1-3), diagnosis (CQs 4 and 5), and treatment (two CQs 6 and 7). In each statement, the consensus rate, evidence level, and recommendation level were determined. CONCLUSION The guidelines will be helpful in the management of children with hepatitis C MTC transmission.
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Affiliation(s)
- Hitoshi Tajiri
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Kazuhiko Bessho
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
| | - Daiki Abukawa
- Division of General Pediatrics and Gastroenterology, Miyagi Children's Hospital, Sendai, Japan
| | - Yoshinori Iitsuka
- Department of Obstetrics & Gynecology, Chiba Kaihin Municipal Hospital, Chiba, Japan
| | - Yoshinori Ito
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Yokohama, Japan
| | - Yuri Etani
- Department of Gastroenterology Nutrition and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tomoko Takano
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yoko Miyoshi
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Jun Murakami
- Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan
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30
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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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31
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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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32
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One-Year Outcomes after Ledipasvir/Sofosbuvir Treatment of Chronic Hepatitis C in Teenagers with and without Significant Liver Fibrosis-A Case Series Report. Viruses 2021; 13:v13081518. [PMID: 34452383 PMCID: PMC8402679 DOI: 10.3390/v13081518] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/25/2021] [Accepted: 07/28/2021] [Indexed: 12/15/2022] Open
Abstract
One-year outcomes after therapy with ledipasvir/sofosbuvir (LDV/SOF) in children with chronic hepatitis C (CHC) presenting with and without significant liver fibrosis were analyzed. We included patients aged 12-17 years treated with LDV/SOF, presenting with significant fibrosis (F ≥ 2 on the METAVIR scale) in transient elastography (TE) at the baseline and we compared the outcomes with that of patients without fibrosis. Patients were followed every 4 weeks during the treatment, at the end of the therapy, at week 12 posttreatment, and one year after the end of treatment. Liver fibrosis was established using noninvasive methods: TE, aspartate transaminase-to-platelet ratio index (APRI), and Fibrosis-4 index (FIB-4). There were four patients with significant fibrosis at baseline: one with a fibrosis score of F2 on the METAVIR scale, and three with cirrhosis (F4) at baseline. One year after the end of treatment, the hepatitis C viral load was undetectable in three of them. One patient was lost to follow-up after week 4. In two out of the four patients, a significant improvement and regression of liver fibrosis was observed (from stage F4 and F2 to F0-F1 on the METAVIR scale). In one patient, the liver stiffness measurement median increased 12 weeks after the end of the treatment and then decreased, but still correlated with stage F4. An improvement in the APRI was observed in all patients. In four patients without fibrosis, the treatment was effective and no progression of fibrosis was observed. A one-year observation of teenagers with CHC and significant fibrosis treated with LDV/SOF revealed that regression of liver fibrosis is possible, but not certain. Further observations in larger groups of patients are necessary to find predictors of liver fibrosis regression.
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33
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Jonas MM, Rhee S, Kelly DA, Del Valle‐Segarra A, Feiterna‐Sperling C, Gilmour S, Gonzalez‐Peralta RP, Hierro L, Leung DH, Ling SC, Lobzin Y, Lobritto S, Mizuochi T, Narkewicz MR, Sabharwal V, Wen J, Kei Lon H, Marcinak J, Topp A, Tripathi R, Sokal E. Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study. Hepatology 2021; 74:19-27. [PMID: 33811356 PMCID: PMC8548879 DOI: 10.1002/hep.31841] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 02/25/2021] [Accepted: 03/22/2021] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV-infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years. APPROACH AND RESULTS Children with chronic HCV infection, genotype 1-6, with or without compensated cirrhosis, were divided into three cohorts by age-cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)-and given weight-based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (SVR12) and steady-state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug-related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults. CONCLUSIONS A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV-infected children 3 to < 12 years old.
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Affiliation(s)
- Maureen M. Jonas
- Division of Gastroenterology, Hepatology, and NutritionBoston Children’s HospitalBostonMA
- Department of PediatricsHarvard Medical SchoolBostonMA
| | | | - Deirdre A. Kelly
- The Liver UnitBirmingham Women’s & Children’s Hospital and University of BirminghamBirminghamUnited Kingdom
| | | | - Cornelia Feiterna‐Sperling
- Department of Pediatric Pulmonology, Immunology, and Intensive Care MedicineCharité–Universitätsmedizin BerlinBerlinGermany
| | - Susan Gilmour
- Stollery Children’s Hospital and University of AlbertaEdmontonABCanada
| | | | | | - Daniel H. Leung
- Division of Gastroenterology, Hepatology, and NutritionTexas Children’s HospitalHoustonTX
- Department of PediatricsBaylor College of MedicineHoustonTX
| | - Simon C. Ling
- Division of Gastroenterology, Hepatology, and NutritionThe Hospital for Sick ChildrenTorontoONCanada
- Department of PaediatricsUniversity of TorontoTorontoONCanada
| | - Yuri Lobzin
- Pediatric Research and Clinical Center for Infectious Diseases and North‐Western State Medical University named after I.I. MechnikovRussian FederationSt. PetersburgRussia
| | - Steven Lobritto
- Morgan Stanley Children’s Hospital of New YorkColumbia University Irving Medical CenterNew YorkNY
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child HealthKurume University School of MedicineKurumeJapan
| | - Michael R. Narkewicz
- Digestive Health InstituteChildren’s Hospital ColoradoSection of Pediatric GastroenterologyHepatology, and NutritionDepartment of Pediatrics University of Colorado School of MedicineAuroraCO
| | - Vishakha Sabharwal
- Division of Pediatric Infectious DiseasesDepartment of PediatricsBoston University Medical CenterBostonMA
| | - Jessica Wen
- The Children’s Hospital Philadelphia and University of PennsylvaniaPhiladelphiaPA
| | | | | | | | | | - Etienne Sokal
- Division of Pediatric Gastroenterology and HepatologyUniversité Catholique de LouvainCliniques Universitaires Saint LucBrusselsBelgium
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Fu Z, Dong C, Ge Z, Wang C, Zhang Y, Shen C, Li J, Zhu C, Wang Y, Huang P, Yue M. High SVR12 With 8-Week Course of Direct-Acting Antivirals in Adolescents and Children With Chronic Hepatitis C: A Comprehensive Analysis. Front Med (Lausanne) 2021; 8:608760. [PMID: 34169081 PMCID: PMC8217461 DOI: 10.3389/fmed.2021.608760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 04/30/2021] [Indexed: 11/13/2022] Open
Abstract
Direct-acting antiviral (DAA) treatment for 8 weeks has a sustained virological response rate in adults with chronic hepatitis C. We have conducted a systematic review and meta-analysis to compare the efficacy and safety of the 8-week vs. 12/24-week DAA treatment in adolescents and children with CHC. The PubMed, Web of Science, and Cochrane databases were searched for the relevant articles from January 1, 2017 to August 28, 2020 and further screened for literature reviews on April 1, 2021. Pool proportions with 95% CIs for SVR12 were summarized with fixed/random effects models using Freeman-Tukey double arcsine transformation. Subgroup analysis was used to explore the source of heterogeneity. Thirty-six relevant publications were identified. For adolescents aged 12-17 years old, the pooled SVR12 and AE rate were 99.4% (95% CI: 98.7-99.9) and 34.7% (95% CI: 31.9-37.6). No one discontinued treatment due to drug intolerance. In addition, the SVR12 adolescents treated for 12 and 8/24 weeks were 99.3% (95% CI: 98.4-99.9) and 100%, respectively. The pooled SVR12 rate, AEs, and SAEs for children younger than 12 years were 98.9% (95% CI: 97.3-99.8), 51.6% (95% CI: 47.0-56.2), and 1.1% (95% CI: 0.4-2.5), respectively. The most common AE was fatigue (28.4%). The SVR12 was 98.8% (95% CI: 97.1-99.8) and 100% for the pediatric patients treated for 12 weeks and 8/24 weeks, respectively. Taken together, DAAs are generally effective against CHC and well-tolerated by the adolescents and children. A treatment duration of 8 weeks is equally effective and safe as 12/24 weeks in this demographic group.
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Affiliation(s)
- Zuqiang Fu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Eastern Theater Command Centers for Disease Control and Prevention, Institute of Epidemiology and Microbiology, Nanjing, China
| | - Chen Dong
- Department of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Zhijun Ge
- Department of Critical Care Medicine, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Chunhui Wang
- Eastern Theater Command Centers for Disease Control and Prevention, Institute of Epidemiology and Microbiology, Nanjing, China
| | - Yun Zhang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Eastern Theater Command Centers for Disease Control and Prevention, Institute of Epidemiology and Microbiology, Nanjing, China
| | - Chao Shen
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Eastern Theater Command Centers for Disease Control and Prevention, Institute of Epidemiology and Microbiology, Nanjing, China
| | - Jun Li
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chuanlong Zhu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan Wang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Peng Huang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Eastern Theater Command Centers for Disease Control and Prevention, Institute of Epidemiology and Microbiology, Nanjing, China
| | - Ming Yue
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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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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36
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Wirth S, Schreiber-Dietrich D, Dietrich CF. Aktuelle Therapie der chronischen Hepatitis C bei Kindern und Jugendlichen. Monatsschr Kinderheilkd 2021; 169:534-541. [DOI: 10.1007/s00112-021-01122-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 01/05/2021] [Indexed: 02/07/2023]
Abstract
ZusammenfassungZur Behandlung der chronischen Hepatitis C wurden in den letzten Jahren direkt wirkende antivirale Medikamente (DAA) zugelassen und sind bei Erwachsenen etabliert. Sie machten die interferonbasierten Therapien obsolet. Auch für Kinder und Jugendliche stehen seit Kurzem einige DAA zur Verfügung, die überwiegend ab dem Alter von 3 Jahren eingesetzt werden können.Die chronische Hepatitis C wird bei Kindern überwiegend vertikal übertragen und ist selten. Sie ist zwar zunächst eine wenig aktive und progrediente Erkrankung, kann aber im Erwachsenenalter in eine Leberzirrhose mit der Folge eines hepatozellulären Karzinoms übergehen. Die Diagnose ist mit der Bestimmung des Anti-HCV (IgM/IgG) und der HCV-RNA im Serum mit Genotypisierung leicht zu stellen. Die DAA werden oral appliziert und ausgesprochen gut toleriert. Drei Wirkstoffkombinationen stehen aktuell zur Verfügung, und 2021 wird eine weitere zugelassen. Die Heilungschancen sind mit über 95 % ausgesprochen gut und anhaltend.Im eigenen Krankengut wurden 25 Jungen und Mädchen überwiegend mit Genotyp 1 im Alter von 4 bis 17 Jahren mit DAA behandelt. Unabhängig von der Höhe der HCV-RNA im Serum waren alle bereits nach 4 Wochen HCV-RNA negativ und erzielten einen dauerhaften Erfolg.Die wesentliche Aufgabe ist nun, alle Kinder und Jugendlichen mit einer chronischen Hepatitis C zu identifizieren. Bei der äußerst guten Heilungschance kann davon ausgegangen werden, dass das Eradikationsziel in dieser Altersgruppe in absehbarer Zeit erreicht werden kann.
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37
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Nicastro E, Norsa L, Di Giorgio A, Indolfi G, D'Antiga L. Breakthroughs and challenges in the management of pediatric viral hepatitis. World J Gastroenterol 2021; 27:2474-2494. [PMID: 34092970 PMCID: PMC8160618 DOI: 10.3748/wjg.v27.i20.2474] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/04/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) major causes of advanced liver disease and mortality worldwide. Although regarded as benign infections in children, their persistence through adulthood is undoubtedly of concern. Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment, which is currently far from being curative. Herein we describe direct-acting antivirals available for pediatric HCV (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) and their real-world use. A critical review of the HBV pediatric classification is provided. Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population, including capsid assembly modulators, antigen secretion inhibitors, silencing RNAs, and immune modifiers. Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.
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Affiliation(s)
- Emanuele Nicastro
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Lorenzo Norsa
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Angelo Di Giorgio
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Giuseppe Indolfi
- Department of Neurofarba, Meyer Children's University Hospital of Florence, Florence 50137, Italy
| | - Lorenzo D'Antiga
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
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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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Rogers ME, Balistreri WF. Cascade of care for children and adolescents with chronic hepatitis C. World J Gastroenterol 2021;27:1117-1131. [PMID: 33828389 PMCID: PMC8006101 DOI: 10.3748/wjg.v27.i12.1117] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/19/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection presents a significant global public health burden. In 2015, over 400000 deaths worldwide were attributed to HCV infection. This led the World Health Organization (WHO) in 2016 to set the ambitious goal of eliminating HCV by 2030. Adult-centered guidelines have been established in order to provide direction for healthcare professionals, allowing integration of the newest screening policies and therapeutic strategies into their practices. However, for children and adolescents, HCV is a significant, unrecognized public health problem. HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic. An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States, with approximately 1700 of their infants being infected with HCV. Newer HCV-specific therapeutics, namely direct acting antivirals (DAA), has brought a new and highly successful approach to treatment of hepatitis C. Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population. Thus, an enhanced cascade of care, which should include the population under 18 years of age, can help achieve the WHO goal by focusing on elimination in the youngest populations. This review will present an overview of the natural history, clinical features, and management of HCV in children and adolescents.
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Affiliation(s)
- Michael Evan Rogers
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
| | - William F Balistreri
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
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40
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Chappell CA, Jonas MM. Hepatitis C Virus in Pregnancy: Are We Ready for Test and Treat? J Infect Dis 2021; 222:S789-S793. [PMID: 33245353 DOI: 10.1093/infdis/jiaa181] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Catherine A Chappell
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
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41
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Pokorska-Śpiewak M, Dobrzeniecka A, Lipińska M, Tomasik A, Aniszewska M, Marczyńska M. Liver Fibrosis Evaluated With Transient Elastography in 35 Children With Chronic Hepatitis C Virus Infection. Pediatr Infect Dis J 2021; 40:103-108. [PMID: 33021594 DOI: 10.1097/inf.0000000000002913] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this prospective study was to analyze liver fibrosis in teenagers with chronic hepatitis C (CHC) using noninvasive methods. METHODS Thirty-five patients with CHC, 12-17 years of age (mean 14.2 ± 1.8 years; 22/35, 63% male) were included. Most of them (29/35, 83%) were infected vertically, 21/35 (60%) were treatment-naive, 30/35 (86%) were infected with genotype 1 and 5/35 (14%) were infected with genotype 4 HCV. In all patients, evaluation of liver fibrosis was performed using transient elastography (TE) and measurement of the following serum biomarkers: aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4). Using liver stiffness measurement (LSM) results as a reference, the diagnostic performance of APRI and FIB-4 was assessed by calculating area under the receiver operating characteristics curve. RESULTS Transient elastography results revealed no or mild fibrosis (F0/1 in METAVIR scale) in 31/35 (89%) patients. In 4/35 (11%) patients, significant fibrosis was observed (F ≥ 2), including 3/35 (9%) with cirrhosis (F4). The median APRI was 0.32, and the median FIB-4 was 0.32. LSM was associated with both APRI and FIB-4 [r = 0.61, 95% confidence interval (CI) 0.35-0.79, P = 0.0001; and r = 0.60, 95% CI 0.32-0.78, P = 0.0002, respectively]. For the diagnosis of significant fibrosis, the area under the receiver operating characteristics (95% CI) for both APRI and FIB-4 was 0.855 (0.695-0.951). APRI, with a cutoff >0.374, predicted significant fibrosis, with 100% sensitivity and 67.7% specificity, whereas FIB-4, with a cutoff >0.402, predicted significant fibrosis, with 75.0% sensitivity and 90.3% specificity. CONCLUSIONS Significant fibrosis, including cirrhosis, may occur in teenagers with CHC. Serum biomarkers (APRI, FIB-4) correlate positively with LSM.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Dobrzeniecka
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Marta Lipińska
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Tomasik
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, 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
- Pediatric Infectious Diseases Unit, 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
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
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Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children. KLINISCHE PADIATRIE 2020; 233:211-215. [PMID: 33339066 DOI: 10.1055/a-1304-3542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.
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43
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Clemente MG, Antonucci R, Sotgiu G, Dettori M, Piana A, Vajro P. Present and future management of viral hepatitis B and C in children. Clin Res Hepatol Gastroenterol 2020; 44:801-809. [PMID: 32173307 DOI: 10.1016/j.clinre.2020.02.010] [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: 07/07/2019] [Revised: 01/19/2020] [Accepted: 02/07/2020] [Indexed: 02/07/2023]
Abstract
Having a hepatitis B virus (HBV) or hepatitis C virus (HCV) infection places a child at higher risk for subsequent chronic hepatitis B (CHB) or chronic hepatitis C (CHC) infection. The risk of mother-to-child transmission is higher for HBV (20% to 90%) than for HCV (<5%). Perinatal HBV infection generally causes CHB infection while perinatal HCV infection has a certain rate of spontaneous viral clearance (around 20% to 30%). Of the two, only HBV infection can benefit from passive/active perinatal immunoprophylaxis. The risk of CHB in children with HBV horizontal transmission decreases with age, whereas HCV transmission among teenagers commonly results into a long-life infection and CHC infection. Children with CHB or CHC should be carefully assessed for the need for antiviral treatment. When treatment cannot be deferred, pediatric CHB infection has different first-line treatment options: standard interferon (for children aged≥1 year), pegylated interferon (for children aged≥3 years), and the oral nucleotide analogues entecavir (for children aged≥2 years) and tenofovir (for children aged≥12 years). The choice of treatment depends on the child's age, virus genotypes, previous treatment failure and presence of contraindications. Expected responsiveness rate is 25% of hepatitis B e-antigen clearance, with both standard interferon and nucleotide analogues. Direct antiviral agents are first-line treatment for CHC infection in children aged 3 years or older. Hepatitis C virus sustained virus response is as high as 97%. Therefore, if direct antiviral agents can be proven to be safe and well tolerated in very young children, HCV eradication could be planned after the first screening.
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Affiliation(s)
- Maria Grazia Clemente
- Pediatric Clinic, Clinical Epidemiology and Medical Statistics Unit, Hygiene and Preventive Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari (SS), Italy.
| | - Roberto Antonucci
- Pediatric Clinic, Clinical Epidemiology and Medical Statistics Unit, Hygiene and Preventive Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari (SS), Italy
| | - Giovanni Sotgiu
- Pediatric Clinic, Clinical Epidemiology and Medical Statistics Unit, Hygiene and Preventive Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari (SS), Italy
| | - Marco Dettori
- Pediatric Clinic, Clinical Epidemiology and Medical Statistics Unit, Hygiene and Preventive Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari (SS), Italy
| | - Andrea Piana
- Pediatric Clinic, Clinical Epidemiology and Medical Statistics Unit, Hygiene and Preventive Medicine, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari (SS), Italy
| | - Pietro Vajro
- Pediatrics - Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi (SA), Italy
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44
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Indolfi G, Giometto S, Serranti D, Bettiol A, Bigagli E, De Masi S, Lucenteforte E. Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection. Aliment Pharmacol Ther 2020; 52:1125-1133. [PMID: 32809230 DOI: 10.1111/apt.16037] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 04/27/2020] [Accepted: 07/22/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. AIM To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. METHODS We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses. RESULTS Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. CONCLUSIONS Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.
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Affiliation(s)
- Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy.,Department NEUROFARBA, University of Florence, Florence, Italy
| | - Sabrina Giometto
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Daniele Serranti
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | | | | | - Salvatore De Masi
- Clinical Trial Office, Meyer's Children University Hospital of Florence, Firenze, Italy
| | - Ersilia Lucenteforte
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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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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Hepatitis C in Children and Adolescents of a Brazilian Tertiary Center: Identifying Patients Eligible for Direct-Acting Antivirals. Pediatr Infect Dis J 2020; 39:e276-e278. [PMID: 32496409 DOI: 10.1097/inf.0000000000002725] [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] [Indexed: 11/26/2022]
Abstract
We evaluated 113 pediatric patients with chronic hepatitis C from 2009 to 2019 at a Brazilian tertiary center. Seventy patients received pegylated-interferon treatment. The sustained virologic response was 61.4%, and 92.8% reported side effects. Currently, we are following 39 patients with chronic hepatitis C, 24 of whom are eligible for treatment with direct-acting antivirals according to Brazilian recommendations.
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Pokorska-Śpiewak M, Śpiewak M. Management of hepatitis C in children and adolescents during COVID-19 pandemic. World J Hepatol 2020; 12:485-492. [PMID: 32952875 PMCID: PMC7475775 DOI: 10.4254/wjh.v12.i8.485] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/20/2020] [Accepted: 07/26/2020] [Indexed: 02/06/2023] Open
Abstract
In recent years, significant progress in the antiviral treatment of chronic hepatitis C (CHC) has been made due to the development of interferon-free therapies. Three different highly effective, oral direct-acting antiviral (DAA) regimens have been approved for use in adolescents with CHC between the ages of 12-years-old and 17-years-old in Europe. According to the current recommendations, all treatment-naïve and treatment-experienced children with CHC virus infection should be considered for DAA therapy to prevent the possible progression of hepatitis C virus-related liver disease and its complications. However, the novel coronavirus disease 2019 outbreak, which was classified as a pandemic in March 2020, is currently spreading throughout the world, resulting in a disruption of the healthcare system. This disruption is having a negative impact on the care of patients with chronic diseases, including children with CHC. Thus, several efforts have to be made by pediatric hepatologists to prioritize patient care in children with CHC. These efforts include promoting telemedicine in the outpatient setting, using local laboratory testing for follow-up visits, and engaging in the home delivery of DAAs for patients under antiviral therapy whenever possible.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw 01201, Poland
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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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Smith SK. Pediatric Hepatitis C. Adv Pediatr 2020; 67:47-56. [PMID: 32591063 DOI: 10.1016/j.yapd.2020.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Sara Kathryn Smith
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco, 550 16th Street, 5th Floor, Mail Code 0136, San Francisco, CA 94158, USA
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