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Stinco M, Rubino C, Bartolini E, Nuti F, Paolella G, Nebbia G, Silvestro E, Garazzino S, Nicastro E, D'Antiga L, Zanchi C, Morra L, Iorio R, Di Dato F, Maggiore G, Sartorelli MR, Comparcola D, Stracuzzi M, Giacomet V, Musto F, Pinon M, Calvo P, Carloni I, Zallocco F, Cananzi M, Trapani S, Indolfi G. Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study. Liver Int 2025; 45:e16180. [PMID: 39569493 PMCID: PMC11897846 DOI: 10.1111/liv.16180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 10/16/2024] [Accepted: 11/11/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND & AIMS Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC. METHODS This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data. RESULTS Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment. CONCLUSIONS This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.
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Affiliation(s)
| | - Chiara Rubino
- Liver UnitMeyer Children's Hospital IRCCSFlorenceItaly
| | | | - Federica Nuti
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Giulia Paolella
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Gabriella Nebbia
- Pediatric HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Erika Silvestro
- Pediatric Infectious Diseases Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Silvia Garazzino
- Pediatric Infectious Diseases Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Emanuele Nicastro
- Hepatology, Gastroenterology and Transplantation UnitHospital Papa Giovanni XXIIIBergamoItaly
| | - Lorenzo D'Antiga
- Hepatology, Gastroenterology and Transplantation UnitHospital Papa Giovanni XXIIIBergamoItaly
| | - Chiara Zanchi
- Institute for Maternal and Child Health–IRCCS Burlo GarofoloTriesteItaly
| | - Laura Morra
- Pediatric DepartmentUniversity of TriesteTriesteItaly
| | - Raffaele Iorio
- Department of Translational Medical Science, School of Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
| | - Fabiola Di Dato
- Department of Translational Medical Science, School of Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
| | - Giuseppe Maggiore
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Maria Rita Sartorelli
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Donatella Comparcola
- Hepatology, Gastroenterology, Nutrition and Liver Transplantation UnitBambino Gesù Children's Hospital IRCCSRomeItaly
| | - Marta Stracuzzi
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Vania Giacomet
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Francesca Musto
- Pediatric Infectious Disease Unit, Department of Pediatrics, Luigi Sacco HospitalUniversity of MilanMilanItaly
| | - Michele Pinon
- Pediatric Gastroenterology Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Pierluigi Calvo
- Pediatric Gastroenterology Unit, Regina Margherita Children's HospitalUniversity of TurinTurinItaly
| | - Ines Carloni
- Pediatric Infectious Disease UnitSalesi Children HospitalAnconaItaly
| | - Federica Zallocco
- Pediatric Infectious Disease UnitSalesi Children HospitalAnconaItaly
| | - Mara Cananzi
- Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of Children with Liver TransplantationUniversity Hospital of PadovaPadovaItaly
| | - Sandra Trapani
- Pediatric UnitMeyer Children's Hospital IRCCSFlorenceItaly
- Department of Health SciencesUniversity of FlorenceFlorenceItaly
| | - Giuseppe Indolfi
- Liver UnitMeyer Children's Hospital IRCCSFlorenceItaly
- Department of NEUROFARBAUniversity of FlorenceFlorenceItaly
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Ferreira J, Sheflin-Findling S. Update on Pediatric Hepatitis C Infection. Curr Gastroenterol Rep 2025; 27:18. [PMID: 40019674 PMCID: PMC11870864 DOI: 10.1007/s11894-024-00955-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2024] [Indexed: 03/01/2025]
Abstract
PURPOSEOF REVIEW Hepatitis C virus (HCV) infections continue to steadily increase in the United States and remain a major public health challenge. This review aims to provide a comprehensive overview of HCV infection in children, focusing on recent advancements in screening, diagnosis, and treatment. RECENT FINDINGS Effective screening strategies, including universal screening of pregnant women and nucleic acid testing for all perinatally exposed infants at 2 to 6 months of age, have been implemented to identify infected individuals early. Direct-acting antiviral agents have revolutionized treatment, offering high cure rates for children of all ages. Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.
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Affiliation(s)
- Johanna Ferreira
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA.
| | - Shari Sheflin-Findling
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA
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Karnsakul W, Schwarz KB. Hepatitis. REMINGTON AND KLEIN'S INFECTIOUS DISEASES OF THE FETUS AND NEWBORN INFANT 2025:728-744.e4. [DOI: 10.1016/b978-0-323-79525-8.00036-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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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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Nakano S, Suzuki M, Hatori R, Mizuochi T, Etani Y, Tajiri H. Natural history and clinical features of hepatitis C virus infection during childhood: A nationwide, observational survey in Japan. Hepatol Res 2024; 54:795-806. [PMID: 38459826 DOI: 10.1111/hepr.14032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 01/26/2024] [Accepted: 02/12/2024] [Indexed: 03/10/2024]
Abstract
AIM Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. METHODS We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. RESULTS Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031). CONCLUSIONS Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.
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Affiliation(s)
- Satoshi Nakano
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Reiko Hatori
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yuri Etani
- Department of Gastroenterology, Nutrition and Endocrinology, Research Institute Osaka Women's and Children's Hospital, Osaka, Japan
| | - Hitoshi Tajiri
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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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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Panagiotakopoulos L, Miele K, Cartwright EJ, Kamili S, Furukawa N, Woodworth K, Tong VT, Kim SY, Wester C, Sandul AL. CDC's New Hepatitis C Virus Testing Recommendations for Perinatally Exposed Infants and Children: A Step Towards Hepatitis C Elimination. J Womens Health (Larchmt) 2024; 33:695-701. [PMID: 38476092 PMCID: PMC11182722 DOI: 10.1089/jwh.2023.1114] [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] [Indexed: 03/14/2024] Open
Abstract
New U.S. Centers for Disease Control and Prevention (CDC) guidelines for hepatitis C virus (HCV) testing of perinatally exposed infants and children released in 2023 recommend a nucleic acid test (NAT) for detection of HCV ribonucleic acid (i.e., NAT for HCV RNA) at 2-6 months of age to facilitate early identification and linkage to care for children with perinatally acquired HCV infection. Untreated hepatitis C can lead to cirrhosis, liver cancer, and premature death and is caused by HCV, a blood-borne virus transmitted most often among adults through injection drug use in the United States. Perinatal exposure from a birth parent with HCV infection is the most frequent mode of HCV transmission among infants and children. New HCV infections have been increasing since 2010, with the highest rates of infection among people aged 20-39 years, leading to an increasing prevalence of HCV infection during pregnancy. In 2020, the CDC recommended one-time HCV screening for all adults aged 18 years and older and for all pregnant persons during each pregnancy. Detecting HCV infection during pregnancy is key for the identification of pregnant persons, linkage to care for postpartum treatment, and identification of infants with perinatal exposure for HCV testing. It was previously recommended that children who were exposed to HCV during pregnancy receive an antibody to HCV (anti-HCV) test at 18 months of age; however, most children were lost to follow-up before testing occurred, leaving children with perinatal infection undiagnosed. The new strategy of testing perinatally exposed children at age 2-6 months was found to be cost-effective in increasing the identification of infants who might develop chronic hepatitis C. This report describes the current perinatal HCV testing recommendations and how they advance national hepatitis C elimination efforts by improving the health of pregnant and postpartum people and their children.
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Affiliation(s)
| | - Kathryn Miele
- Division of Birth Defects and Infant Disorders, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Emily J. Cartwright
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Nathan Furukawa
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Kate Woodworth
- Division of Birth Defects and Infant Disorders, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Van T. Tong
- Division of Birth Defects and Infant Disorders, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Shin Y. Kim
- Division of Birth Defects and Infant Disorders, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Carolyn Wester
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Amy L. Sandul
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Laily A, Duncan R, Gabhart KM, Nephew LD, Christy SM, Vadaparampil ST, Giuliano AR, Kasting ML. Differences in Provider Hepatitis C Virus Screening Recommendations by Patient Risk Status. Prev Med Rep 2024; 38:102602. [PMID: 38375175 PMCID: PMC10874862 DOI: 10.1016/j.pmedr.2024.102602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 01/05/2024] [Accepted: 01/06/2024] [Indexed: 02/21/2024] Open
Abstract
Providers' recommendation is among the strongest predictors to patients engaging in preventive care. Therefore, the aim of this study was to compare providers' Hepatitis C Virus (HCV) screening recommendation quality between high-risk and average-risk patients to determine if providers are universally recommending HCV screening, regardless of risk behaviors. This cross-sectional survey of 284 Indiana providers in 2020 assessed provider characteristics, HCV screening recommendation practices (strength, presentation, frequency, timeliness), self-efficacy, and barriers to recommending HCV screening. T-test and Chi-square compared recommendation practices for high-risk and average-risk patients. Prevalence ratios were calculated for variables associated with HCV recommendation strength comparing high-risk and average-risk patients. Logistic regression analyses examined factors associated with HCV recommendation strength for high- and average-risk patients, with odds ratios. Compared to average-risk patients, high-risk patients received higher proportion of HCV recommendations that were strong (70.4 % v. 42.4 %), routine (61.9 % v. 55.6 %), frequent (37.7 % v. 28 %), and timely (74.2 % v. 54.9 %) (P-values < 0.001). Compared to average-risk patients, providers with high-risk patients had a lower percentage of giving a strong recommendation if they were nurse practitioner (PR = 0.49). For high-risk patients, providers with higher self-efficacy (aOR = 2.16;95 %CI = 0.99-4.69) had higher odds, while those with higher perceived barriers (aOR = 0.19;95 %CI = 0.09-0.39) and those with an internal medicine specialty compared to family medicine (aOR = 0.22;95 %CI = 0.08-0.57) had lower odds of giving a strong recommendation. These data suggest providers are not universally recommending HCV screening for all adults regardless of reported risk. Future research should translate these findings into multilevel interventions to improve HCV screening recommendations regardless of patient risk status.
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Affiliation(s)
- Alfu Laily
- Department of Public Health, College of Health and Human Sciences, Purdue University, 820 Mitch Daniels Blvd, West Lafayette, IN 47907, USA
| | - Robert Duncan
- Department of Human Development and Family Studies, College of Health and Human Sciences, Purdue University, 1202 West State St., West Lafayette, IN 47907, USA
| | - Kaitlyn M. Gabhart
- Department of Psychology, Vanderbilt University, 230 Appleton Pl, Nashville, TN 37203, USA
| | - Lauren D. Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 340 W 10th St., Indianapolis, IN 46202, USA
| | - Shannon M. Christy
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Department of Oncological Sciences, University of South Florida, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
| | - Susan T. Vadaparampil
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Department of Oncological Sciences, University of South Florida, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
| | - Anna R. Giuliano
- Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
- Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
| | - Monica L. Kasting
- Department of Public Health, College of Health and Human Sciences, Purdue University, 820 Mitch Daniels Blvd, West Lafayette, IN 47907, USA
- Cancer Prevention and Control Program, Indiana University Simon Comprehensive Cancer Center, 535 Barnhill Dr., Indianapolis, IN 46202, USA
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STOKES CALEB, J. MELVIN ANN. Viral Infections of the Fetus and Newborn. AVERY'S DISEASES OF THE NEWBORN 2024:450-486.e24. [DOI: 10.1016/b978-0-323-82823-9.00034-9] [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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Panagiotakopoulos L, Sandul AL, Conners EE, Foster MA, Nelson NP, Wester C. CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children - United States, 2023. MMWR Recomm Rep 2023; 72:1-21. [PMID: 37906518 PMCID: PMC10683764 DOI: 10.15585/mmwr.rr7204a1] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2023] Open
Abstract
The elimination of hepatitis C is a national priority (https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf). During 2010-2021, hepatitis C virus (HCV) acute and chronic infections (hereinafter referred to as HCV infections) increased in the United States, consequences of which include cirrhosis, liver cancer, and death. Rates of acute infections more than tripled among reproductive-aged persons during this time (from 0.8 to 2.5 per 100,000 population among persons aged 20-29 years and from 0.6 to 3.5 among persons aged 30-39 years). Because acute HCV infection can lead to chronic infection, this has resulted in increasing rates of HCV infections during pregnancy. Approximately 6%-7% of perinatally exposed (i.e., exposed during pregnancy or delivery) infants and children will acquire HCV infection. Curative direct-acting antiviral therapy is approved by the Food and Drug Administration for persons aged ≥3 years. However, many perinatally infected children are not tested or linked to care. In 2020, because of continued increases in HCV infections in the United States, CDC released universal screening recommendations for adults, which included recommendations for screening for pregnant persons during each pregnancy (Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC recommendations for hepatitis C screening among adults-United States, 2020. MMWR Recomm Rep 2020;69[No. RR-2]:1-17). This report introduces four new CDC recommendations: 1) HCV testing of all perinatally exposed infants with a nucleic acid test (NAT) for detection of HCV RNA at age 2-6 months; 2) consultation with a health care provider with expertise in pediatric hepatitis C management for all infants and children with detectable HCV RNA; 3) perinatally exposed infants and children with an undetectable HCV RNA result at or after age 2 months do not require further follow-up unless clinically warranted; and 4) a NAT for HCV RNA is recommended for perinatally exposed infants and children aged 7-17 months who previously have not been tested, and a hepatitis C virus antibody (anti-HCV) test followed by a reflex NAT for HCV RNA (when anti-HCV is reactive) is recommended for perinatally exposed children aged ≥18 months who previously have not been tested. Proper identification of perinatally infected children, referral to care, and curative treatment are critical to achieving the goal of hepatitis C elimination.
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Affiliation(s)
| | - Amy L Sandul
- Division
of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB
prevention, CDC; Division of Global Health Protection, Center for Global
Health, CDC
| | - DHSc1
- Division
of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB
prevention, CDC; Division of Global Health Protection, Center for Global
Health, CDC
| | | | | | | | | | - Collaborators
- Division
of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB
prevention, CDC; Division of Global Health Protection, Center for Global
Health, CDC
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Hall EW, Panagiotakopoulos L, Wester C, Nelson N, Sandul AL. Cost-Effectiveness of Strategies to Identify Children with Perinatally Acquired Hepatitis C Infection. J Pediatr 2023; 258:113409. [PMID: 37023948 PMCID: PMC10448738 DOI: 10.1016/j.jpeds.2023.113409] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 02/24/2023] [Accepted: 03/25/2023] [Indexed: 04/08/2023]
Abstract
OBJECTIVE To determine the optimal testing strategy to identify children with perinatally acquired hepatitis C virus (HCV) infection. STUDY DESIGN We used a decision-tree framework with a Markov disease progression model to conduct an economic analysis of 4 strategies, based on combinations of type and timing of test: anti-HCV with reflex to HCV RNA at 18 months among children known to be perinatally exposed (ie, baseline comparison strategy); HCV RNA testing at 2-6 months among infants known to be perinatally exposed (test strategy 1); universal anti-HCV with reflex to HCV RNA at 18 months among all children (test strategy 2); and universal HCV RNA testing at 2-6 months among all infants (test strategy 3). We estimated total cost, quality-adjusted life years, and disease sequalae for each strategy. RESULTS Each of the 3 alternative testing strategies resulted in an increased number of children tested and improved health outcomes. HCV RNA testing at 2-6 months (test strategy 1) was cost-saving and resulted in a population-level difference in cost of $469 671. The 2 universal testing strategies resulted in an increase in quality-adjusted life years and an increase in total costs. CONCLUSIONS Testing of perinatally exposed infants at age 2-6 months with a single HCV RNA test will reduce costs and improve health outcomes, preventing morbidity and mortality associated with complications from perinatal HCV infections.
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Affiliation(s)
- Eric W Hall
- OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR.
| | - Lakshmi Panagiotakopoulos
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Carolyn Wester
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Noele Nelson
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Amy L Sandul
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
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Ades AE, Gordon F, Scott K, Collins IJ, Thorne C, Pembrey L, Chappell E, Mariné-Barjoan E, Butler K, Indolfi G, Gibb DM, Judd A. Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment. Clin Infect Dis 2023; 76:913-991. [PMID: 35396848 PMCID: PMC9989140 DOI: 10.1093/cid/ciac255] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. METHODS Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA-negative infants in whom RNA was not detectable until after 6 weeks. RESULTS Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1-18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0-76.9), 39.7% (CrI, 17.9-65.9), and 20.9% (CrI, 4.6-44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. CONCLUSIONS Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment.
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Affiliation(s)
- A E Ades
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Fabiana Gordon
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Karen Scott
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Intira Jeannie Collins
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Claire Thorne
- Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Lucy Pembrey
- Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Elizabeth Chappell
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Eugènia Mariné-Barjoan
- Public Health Department, Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, Nice, France
| | - Karina Butler
- Children’s Health Ireland at Crumlin and Temple Street, Dublin, Ireland
| | - Giuseppe Indolfi
- Meyer Children’s Hospital and Department Neurofarba, University of Florence, Firenze, Italy
| | - Diana M Gibb
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Ali Judd
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
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13
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Ades AE, Gordon F, Scott K, Collins IJ, Claire T, Pembrey L, Chappell E, Mariné-Barjoan E, Butler K, Indolfi G, Gibb DM, Judd A. Overall Vertical Transmission of Hepatitis C Virus, Transmission Net of Clearance, and Timing of Transmission. Clin Infect Dis 2023; 76:905-912. [PMID: 35403676 PMCID: PMC9989130 DOI: 10.1093/cid/ciac270] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 02/11/2022] [Accepted: 04/05/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%-6% in monoinfected women, and that 25%-40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates "net" of clearance. METHODS We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. RESULTS Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%-8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%-16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%-4.1%), and 4.1% (95% CrI, 1.7%-7.3%). We estimated that 24.8% (95% CrI, 12.1%-40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%-83.3%) later in utero, and 9.3% (95% CrI, 0.5%-30.6%) during delivery. CONCLUSIONS Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.
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Affiliation(s)
- Anthony E Ades
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Fabiana Gordon
- Population Health Sciences, University of Bristol Medical School, Bristol, United Kingdom
| | - Karen Scott
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Intira J Collins
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Thorne Claire
- Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Lucy Pembrey
- Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Elizabeth Chappell
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Eugènia Mariné-Barjoan
- Université Côte d’Azur, Public Health Department, Centre Hospitalier Universitaire de Nice, Nice, France
| | - Karina Butler
- Children's Health Ireland at Crumlin and Temple Street, Dublin, Ireland
| | - Giuseppe Indolfi
- Meyer Children's Hospital and Department Neurofarba, University of Florence, Firenze, Italy
| | - Diana M Gibb
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
| | - Ali Judd
- Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom
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14
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Pediatric Hepatitis C Quality Improvement Project Improves Healthcare Access. J Pediatr Gastroenterol Nutr 2023; 76:371-378. [PMID: 36728827 DOI: 10.1097/mpg.0000000000003690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES Incidence of hepatitis C virus (HCV) infection is increasing in women of reproductive age, leading to increased prevalence of HCV infection in children via vertical transmission. This quality improvement (QI) project aimed to increase referrals to and appointments scheduled with a specialty pediatric gastroenterology HCV clinic and the number of eligible children with HCV who completed treatment. METHODS From July 2020 to August 2021, the QI team designed a project using the Model for Improvement and completed Plan Do Study Act cycles to test change ideas to improve HCV awareness and education for medical providers and families; standardize the referral process; track patients; increase clinic capacity; and connect families with community resource care coordination. Referrals to the pediatric HCV clinic, appointments scheduled, no shows, and treatment follow-up were tracked during the project period and a comparison timeframe from July 2019 to June 2020. RESULTS There were improvements in several measures during the project period versus the comparison timeframe, with 80 versus 48 referrals received (66% increase), 115 versus 59 scheduled clinic visits (95% increase), and 7 versus 5 treatment completers (40% increase), along with a small (7%) decline in the proportion of scheduled clinic visits that were no shows. CONCLUSION Application of QI methodology increased medical provider and caregiver awareness and engagement in accessing HCV healthcare available for at-risk children. More QI efforts should be accelerated to identify best practices amidst a nationwide HCV epidemic.
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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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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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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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Yakimova AV, Mukhamedshina VR, Kucherenko SG. Viral hepatitis C during pregnancy: prevalence, impact on perinatal outcomes, patient management tactics (literature review). CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.7.201799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The article presents modern ideas about the impact of viral hepatitis C on the course of pregnancy, the severity of maternal disease associated with it: methods of delivery and possible vertical transmission. Epidemiological data on the prevalence in the world and the Russian Federation, risk factors for perinatal HCV transmission, and the course of pregnancy in women infected with HCV are shown. The search for the necessary literary sources was carried out in the databases Scopus, PubMed, MedLine, The Cochrane Library, RSCI.
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20
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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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21
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Teixeira D, Martins C, Oliveira G, Soares R. Metabolically healthy obesity in a paediatric obesity clinic. J Pediatr Endocrinol Metab 2022; 35:1147-1153. [PMID: 35993884 DOI: 10.1515/jpem-2022-0086] [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: 02/17/2022] [Accepted: 08/01/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Metabolically healthy obese (MHO) children is a described subgroup of obese children who do not exhibit traditional cardiometabolic risk factors. The aim of this study was to determine the prevalence and characterize patients with this phenotype. METHODS Cross-sectional study, performed in a paediatric obesity clinic (tertiary university hospital) in 2019. Children were classified with "MHO" or "metabolically unhealthy obesity" according to the criteria proposed by Damanhoury based on HDL, triglycerides, systolic and diastolic blood pressure (DBP) and fasting glucose values. RESULTS 241 participants were included, with ages between two and 17 years. The prevalence of the MHO phenotype was 61.8%. The body mass index (Z-score) in children aged five years or older was significantly lower in those with MHO (p=0.040). In the MHO group, mean total cholesterol levels were higher (p<0.001), due to the high value of HDL (p<0.001); triglyceride levels (p<0.001), systolic blood pressure (SBP) (p=0.036), DBP (p=0.029) and the homeostasis model assessment - insulin resistance (HOMA-IR) index (p=0.001) were significantly lower. HDL (OR=1.421; 95% CI 1.279-1.579; p<0.001) and SBP (OR=0.943; 95% CI 0.903-0.985; p=0.008) were the only independent predictors for the development of MHO. CONCLUSIONS Almost two-thirds of the participants had an MHO phenotype. The high and low values of HDL and SBP, respectively, were the only variables that proved to be predictors of MHO.
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Affiliation(s)
- Diana Teixeira
- Faculty of Medicine, University Clinic of Paediatrics, University of Coimbra, Coimbra, Portugal
| | - Cátia Martins
- Ambulatory Paediatric Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Guiomar Oliveira
- Faculty of Medicine, University Clinic of Paediatrics, University of Coimbra, Coimbra, Portugal.,Neurodevelopmental and Autism Unit From Child Developmental Centre, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Centro de Investigação e Formação Clínica, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Raquel Soares
- Faculty of Medicine, University Clinic of Paediatrics, University of Coimbra, Coimbra, Portugal.,Ambulatory Paediatric Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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22
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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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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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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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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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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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Gowda C, Smith S, Crim L, Moyer K, Sánchez PJ, Honegger JR. Nucleic Acid Testing for Diagnosis of Perinatally Acquired Hepatitis C Virus Infection in Early Infancy. Clin Infect Dis 2021; 73:e3340-e3346. [PMID: 32640018 PMCID: PMC8563185 DOI: 10.1093/cid/ciaa949] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Most US children with perinatal hepatitis C virus (HCV) exposure fail to receive the recommended anti-HCV antibody test at age ≥18 months. Earlier testing for viral RNA might facilitate increased screening, but sensitivity of this approach has not been established. We hypothesized that modern HCV-RNA RT-PCR platforms would adequately detect infected infants. METHODS Nationwide Children's Hospital electronic health records from 1/1/2008 to 30/6/2018 were reviewed to identify perinatally exposed infants tested by HCV-RNA RT-PCR at age 2-6 months. Diagnostic performance was determined using a composite case definition: (1) infected children had positive repeat HCV-RNA testing or positive anti-HCV at age ≥24 months; (2) uninfected children lacked these criteria and had negative anti-HCV at age ≥18 months. RESULTS 770 perinatally exposed infants underwent HCV-RNA testing at age 2-6 months. Of these, 28 (3.6%) tested positive; viremia was confirmed in all who underwent repeat testing (n = 27). Among 742 infants with negative HCV-RNA results, 226 received follow-up anti-HCV testing at age ≥18 months, of whom 223 tested negative. Three children had low-positive anti-HCV results at age 18-24 months that were negative upon retesting after age 24 months, possibly indicating waning maternal antibodies. Using the composite case definitions, early HCV-RNA screening demonstrated sensitivity of 100% (87.5-100%, Wilson-Brown 95% CI) and specificity of 100% (98.3-100%). CONCLUSIONS Modern HCV-RNA RT-PCR assays have excellent sensitivity for early diagnosis of perinatally acquired infection and could aid HCV surveillance given the substantial loss to follow-up at ≥18 months of age.
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Affiliation(s)
- Charitha Gowda
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
- Partners For Kids, Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Stephanie Smith
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Linda Crim
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Katherine Moyer
- Division of Pediatric Infectious Diseases, Inova Children’s Hospital, Falls Church, Virginia USA
| | - Pablo J Sánchez
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
- Division of Neonatology, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
- Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Jonathan R Honegger
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children’s Hospital–The Ohio State University College of Medicine, Columbus, Ohio, USA
- Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
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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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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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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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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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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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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:819-837.e6. [DOI: 10.1016/b978-0-323-67293-1.00075-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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35
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Statler VA, Espinosa C. Management of Hepatitis C in Children and Adolescents. J Pediatric Infect Dis Soc 2020; 9:785-790. [PMID: 33043957 DOI: 10.1093/jpids/piaa114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/10/2020] [Indexed: 12/09/2022]
Abstract
The management of hepatitis C virus (HCV) infections has changed dramatically in recent years with the use of direct antiviral agents (AADs). New AADs have excellent safety profile and demonstrated to be highly effective. Interferon free regimens are now recommended for children and adolescents but significant barriers for treatment exist. Overcoming those barriers will facilitate HCV elimination. This review covers varied topics to familiarize providers with the current status of pediatric HCV management in light of newly available DAAs medications.
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Affiliation(s)
| | - Claudia Espinosa
- Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, USA
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36
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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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Rahal H, Boutros S, Farhat M, Kullar R, Rahal K, Saab S. Estimating paediatric hepatitis C prevalence in the United States. J Viral Hepat 2020; 27:1455-1461. [PMID: 32810350 DOI: 10.1111/jvh.13377] [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: 05/22/2020] [Accepted: 08/07/2020] [Indexed: 12/09/2022]
Abstract
Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates among women, given the assumption that most cases are vertically transmitted. Between 2001 and 2017, maternal HCV infection affected ~ 0.24% of all births, with prevalence increasing by at least 261%. On average, approximately 0.01% of the total number of live births were infected with HCV, with a 245% increase in the number of children born with the infection. HCV epidemiology has evolved, with women of childbearing age representing a greater proportion of infected individuals in the United States, and infants born to infected mothers being at risk. We therefore recommend a greater public health focus of HCV on the paediatric population.
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Affiliation(s)
- Harman Rahal
- Department of Internal Medicine, UCLA Medical Center, Los Angeles, CA, USA
| | - Sandra Boutros
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Mohamad Farhat
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | | | - Kabir Rahal
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Internal Medicine, UCLA Medical Center, Los Angeles, CA, USA.,Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
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38
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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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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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40
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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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41
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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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42
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Kim NG, Kullar R, Khalil H, Saab S. Meeting the WHO hepatitis C virus elimination goal: Review of treatment in paediatrics. J Viral Hepat 2020; 27:762-769. [PMID: 32386099 DOI: 10.1111/jvh.13317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/06/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.
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Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | | | - Haydar Khalil
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
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43
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Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents: A Position Paper of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2020; 70:711-717. [PMID: 32205770 DOI: 10.1097/mpg.0000000000002710] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement. METHODS MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019. RESULTS A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper. All publications were consistent in recommending DAA treatment for adolescents (12-17 years old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies. CONCLUSIONS There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.
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44
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Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for Hepatitis C Screening Among Adults - United States, 2020. MMWR Recomm Rep 2020; 69:1-17. [PMID: 32271723 PMCID: PMC7147910 DOI: 10.15585/mmwr.rr6902a1] [Citation(s) in RCA: 342] [Impact Index Per Article: 68.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8-12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of HCV infection is <0.1% and 2) hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%. The recommendation for HCV testing that remains unchanged is regardless of age or setting prevalence, all persons with risk factors should be tested for hepatitis C, with periodic testing while risk factors persist. Any person who requests hepatitis C testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.
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Affiliation(s)
- Sarah Schillie
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Carolyn Wester
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Melissa Osborne
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - Laura Wesolowski
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
| | - A. Blythe Ryerson
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
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45
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46
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Lopata SM, McNeer E, Dudley JA, Wester C, Cooper WO, Carlucci JG, Espinosa CM, Dupont W, Patrick SW. Hepatitis C Testing Among Perinatally Exposed Infants. Pediatrics 2020; 145:peds.2019-2482. [PMID: 32060140 PMCID: PMC7049945 DOI: 10.1542/peds.2019-2482] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/04/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) prevalence doubled among pregnant women from 2009 to 2014, reaching 3.4 per 1000 births nationwide. Infants exposed to HCV may acquire HCV by vertical transmission. National guidelines recommend that infants exposed to HCV be tested; however, it is unclear if these recommendations are being followed. Our objectives were to determine if infants exposed to HCV were tested and to determine hospital- and patient-level factors associated with differences in testing. METHODS In this retrospective cohort study of infants exposed to HCV who were enrolled in the Tennessee Medicaid program, we used vital statistics-linked administrative data for infants born between January 1, 2005, and December 31, 2014. Infants were followed until 2 years old. Multilevel logistic regression was used to assess the association of HCV testing and hospital- and patient-level characteristics. RESULTS Only 23% of 4072 infants exposed to HCV were tested. Infants whose mothers were white versus African American (96.6% vs 3.1%; P <.001), used tobacco (78% vs 70%; P <.001), and had HIV (1.3% vs 0.4%; P = .002) were more likely to be tested. Infants exposed to HCV who had a higher median of well-child visits (7 vs 6; P <.001) were more likely to be tested. After accounting for maternal and infant characteristics and health care use patterns, African American infants were less likely to undergo general testing (adjusted odds ratio 0.32; 95% confidence interval, 0.13-0.78). CONCLUSIONS Testing occurred in <1 in 4 infants exposed to HCV and less frequently among African American infants. Public health systems need to be bolstered to ensure that infants exposed to HCV are tested for seroconversion.
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Affiliation(s)
| | - Elizabeth McNeer
- Biostatistics, and,Vanderbilt Center for Child Health Policy, Vanderbilt
University Medical Center, Nashville, Tennessee
| | | | - Carolyn Wester
- Tennessee Department of Health, Nashville, Tennessee;
and
| | - William O. Cooper
- Departments of Pediatrics,,Health Policy, and,Vanderbilt Center for Child Health Policy, Vanderbilt
University Medical Center, Nashville, Tennessee
| | | | - Claudia M. Espinosa
- Division of Pediatric Infectious Diseases and,Department of Pediatrics, School of Medicine,
University of Louisville, Louisville, Kentucky
| | | | - Stephen W. Patrick
- Divisions of Neonatology and,Departments of Pediatrics,,Health Policy, and,Vanderbilt Center for Child Health Policy, Vanderbilt
University Medical Center, Nashville, Tennessee
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47
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Saab S, Kullar R, Amini C, Gounder P. WITHDRAWN: The next frontier: universal hepatitis C virus screening in pregnant women. Am J Obstet Gynecol 2020:S0002-9378(20)30133-2. [PMID: 32044311 DOI: 10.1016/j.ajog.2020.01.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 11/04/2019] [Accepted: 01/30/2020] [Indexed: 12/09/2022]
Abstract
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Affiliation(s)
- Sammy Saab
- Departments of Surgery, Medicine, and Nursing, University of California at Los Angeles, Los Angeles, CA
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48
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 513] [Impact Index Per Article: 102.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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49
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Freriksen JJM, van Seyen M, Judd A, Gibb DM, Collins IJ, Greupink R, Russel FGM, Drenth JPH, Colbers A, Burger DM. Review article: direct-acting antivirals for the treatment of HCV during pregnancy and lactation - implications for maternal dosing, foetal exposure, and safety for mother and child. Aliment Pharmacol Ther 2019; 50:738-750. [PMID: 31448450 PMCID: PMC6773363 DOI: 10.1111/apt.15476] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 07/25/2019] [Accepted: 08/02/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct-acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. AIM To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation METHODS: A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. RESULTS Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy-induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. CONCLUSIONS Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.
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Affiliation(s)
- Jolien J M Freriksen
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.,Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Minou van Seyen
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ali Judd
- MRC Clinical Trials Unit at University College London, London, UK
| | - Diana M Gibb
- MRC Clinical Trials Unit at University College London, London, UK
| | - Intira J Collins
- MRC Clinical Trials Unit at University College London, London, UK
| | - Rick Greupink
- Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Frans G M Russel
- Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Angela Colbers
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - David M Burger
- Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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50
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Hardikar W. Viral hepatitis. J Paediatr Child Health 2019; 55:1038-1043. [PMID: 31317618 DOI: 10.1111/jpc.14562] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 12/14/2022]
Abstract
Hepatitis viruses A to E can cause abnormal liver function tests in children. Although, overall, they are relatively uncommon in children in Australia, epidemiology diagnosis and treatment modalities for these viruses have evolved over the last decade. This review provides an update on the diagnosis and treatment of viral hepatitis in children.
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Affiliation(s)
- Winita Hardikar
- Department of Gastroenterology, Royal Children's Hospital, Melbourne, Victoria, Australia
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