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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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Curtis MR, Epstein RL, Pei P, Linas BP, Ciaranello AL. Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus. JAMA Pediatr 2024; 178:489-496. [PMID: 38466273 PMCID: PMC10928541 DOI: 10.1001/jamapediatrics.2024.0114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 01/10/2024] [Indexed: 03/12/2024]
Abstract
Importance Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. Objective To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. Design, Setting, and Participants The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. Interventions The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Main Outcomes and Measures Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). Results The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. Conclusions and Relevance These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.
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Affiliation(s)
- Megan Rose Curtis
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston
- Harvard Medical School, Boston, Massachusetts
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Rachel L. Epstein
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
- Department of Pediatrics, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Pamela Pei
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
| | - Benjamin P. Linas
- Boston Medical Center, Massachusetts
- Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Massachusetts
| | - Andrea L. Ciaranello
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston
- Harvard Medical School, Boston, Massachusetts
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Jarasvaraparn C, Hartley C, Karnsakul W. Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children. Pathogens 2024; 13:180. [PMID: 38392918 PMCID: PMC10891648 DOI: 10.3390/pathogens13020180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46201, USA
| | - Christopher Hartley
- Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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Wasuwanich P, So JM, Presnell B, Karnsakul W, Egerman RS, Wen TS. A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study. Pathogens 2024; 13:45. [PMID: 38251352 PMCID: PMC10821345 DOI: 10.3390/pathogens13010045] [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] [Received: 12/03/2023] [Revised: 12/31/2023] [Accepted: 01/01/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Prevention of the vertical transmission of the hepatitis C virus (HCV) presents an obstetric challenge. There are no approved antiviral medications for the treatment or prevention of HCV for pregnant patients. OBJECTIVE We aimed to create a composite score to accurately identify a population of pregnant patients with HCV who have high potential for vertical transmission. STUDY DESIGN In a retrospective, multicenter cohort study, we identified pregnant patients with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data, including age and race/ethnicity, as well as clinical and laboratory data, including tobacco/alcohol use, infections, liver function tests, the HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count, were collected. Data were analyzed using logistic regression and receiver operating characteristics (ROCs) and internally validated using the forward selection bootstrap method. RESULTS We identified 157 pregnant patients and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141, or 89.8%) were White. A high HCV RNA titer, high absolute lymphocyte count, and high platelet count were associated with vertical transmission. A high HCV RNA titer had an AUROC of 0.815 with sensitivity, specificity, a positive predictive value, and a negative predictive value of 100.0%, 59.1%, 17.6%, and 100.0%, respectively. A composite score combining the three risk factors had an AUROC of 0.902 (95% CI = 0.840-0.964) but with a risk of overfitting. CONCLUSIONS An HCV RNA titer alone or a composite score combining the risk factors for HCV vertical transmission can potentially identify a population of pregnant patients where the rate of vertical transmission is high, allowing for potential interventions during antepartum care.
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Affiliation(s)
- Paul Wasuwanich
- University of Florida College of Medicine, Gainesville, FL 32610, USA; (P.W.); (J.M.S.)
| | - Joshua M. So
- University of Florida College of Medicine, Gainesville, FL 32610, USA; (P.W.); (J.M.S.)
| | - Brett Presnell
- Department of Statistics, University of Florida, Gainesville, FL 32611, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;
| | - Robert S. Egerman
- Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL 32610, USA;
| | - Tony S. Wen
- Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL 32610, USA;
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Panagiotakopoulos L, Sandul AL, DHSc 1, Conners EE, Foster MA, Nelson NP, Wester C, Collaborators. 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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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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Foster MA, Moorman AC, Teshale EH. Hepatitis C Virus. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1156-1160.e3. [DOI: 10.1016/b978-0-323-75608-2.00220-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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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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Parikh BA. Laboratory Strategies for Diagnosis and Monitoring of Hepatis C Virus Infection. CLINICAL MICROBIOLOGY NEWSLETTER 2021; 43:193-203. [DOI: 10.1016/j.clinmicnews.2021.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Treatment of Chronic Hepatitis C in Young Children Reduces Adverse Outcomes and Is Cost-Effective Compared with Deferring Treatment to Adulthood. J Pediatr 2021; 230:38-45.e2. [PMID: 32890583 DOI: 10.1016/j.jpeds.2020.08.088] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/31/2020] [Accepted: 08/28/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the cost-effectiveness of treating young children with chronic hepatitis C virus (HCV) with new direct-acting antivirals. STUDY DESIGN A state-transition model of chronic HCV was developed to conduct a cost-effectiveness analysis comparing treatment at age 6 years vs delaying treatment until age 18 years. Model inputs were derived from recently conducted systematic reviews, published literature, and government statistics. Medical care costs were obtained from linked population level laboratory and administrative data (Ontario, Canada). Outcomes are expressed in expected quality-adjusted life-years and costs (CAD$). Analysis included a base-case to estimate the expected value and one-way and probabilistic sensitivity analyses to evaluate the impact of uncertainty of the model inputs. RESULTS After 20 years, treating 10 000 children early would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths. The incremental cost-effectiveness ratio of early treatment compared to delayed treatment was approximately $12 690/quality-adjusted life-years gained and considered cost-effective. Model results were robust to variation in fibrosis progression rates, disease state-based costs, treatment costs, and utilities. CONCLUSIONS Delaying treatment until age 18 years results in an increased lifetime risk of late-stage liver complications. Early treatment in children is cost effective. Our work supports clinical and health policies that broaden HCV treatment access to young children.
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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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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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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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14
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Greenaway E, Biondi MJ, Feld JJ, Ling SC. Hepatitis C virus infection in mothers and children. CANADIAN LIVER JOURNAL 2019; 2:210-224. [DOI: 10.3138/canlivj.2019-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 03/28/2019] [Indexed: 12/22/2022]
Abstract
Many unique challenges are associated with hepatitis C infection in mothers and children. The preconception, antenatal, and postnatal phases each offer opportunities to reduce transmission of the virus from mother to infant or to identify the need for treatment. Management of children and youth with hepatitis C is now entering the era of direct-acting antivirals. Improvements are needed in the identification of infected mothers and children and their linkage to appropriate expert care.
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Affiliation(s)
- Emma Greenaway
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Mia J Biondi
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Arthur Labatt Family School of Nursing, Western University, London, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Simon C Ling
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
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15
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Abd-Elgawad MM, Baddour NM, Salem MA. Chronic hepatitis C in children: Clinical spectrum and histopathological study. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2013.03.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
| | - Nahed M. Baddour
- Pathology Department, Faculty of Medicine , Alexandria University , Egypt
| | - Mona A.E. Salem
- Pathology Department, Faculty of Medicine , Alexandria University , Egypt
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16
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Indolfi G, Easterbrook P, Dusheiko G, El-Sayed MH, Jonas MM, Thorne C, Bulterys M, Siberry G, Walsh N, Chang MH, Meyers T, Giaquinto C, Wirth S, Chan PL, Penazzato M. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4:477-487. [PMID: 30982721 DOI: 10.1016/s2468-1253(19)30046-9] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 01/20/2019] [Accepted: 01/22/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1-19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1-3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12-17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas.
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Affiliation(s)
- Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Philippa Easterbrook
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland.
| | - Geoffrey Dusheiko
- King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Manal H El-Sayed
- Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Claire Thorne
- UCL Great Ormond Street Institute of Child Health, University College London, NIHR GOSH BRC, London, UK
| | - Marc Bulterys
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
| | - George Siberry
- Office of the US Global AIDS Coordinator, US Department of State, Washington, DC, USA
| | - Nick Walsh
- Pan American Health Organization, World Health Organization Regional Office for the Americas, Washington, DC, USA
| | - Mei-Hwei Chang
- Department of Paediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Tammy Meyers
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Carlo Giaquinto
- Department of Women and Child Health, University of Padova, Padova, Italy
| | - Stefan Wirth
- Department of Paediatrics, Helios Medical Centre Wuppertal, Witten-Herdecke University, Witten, Germany
| | - Po-Lin Chan
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Martina Penazzato
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
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17
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Modin L, Arshad A, Wilkes B, Benselin J, Lloyd C, Irving WL, Kelly DA. Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol 2019; 70:371-378. [PMID: 30496763 DOI: 10.1016/j.jhep.2018.11.013] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 10/16/2018] [Accepted: 11/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis C virus (HCV) infection is a global health burden. Although HCV infection rarely contributes to morbidity during childhood, most HCV-infected children develop chronic HCV with a lifetime risk of liver disease. Little is known about the development of long-term liver disease and the effect of treatment in patients infected with HCV in childhood. METHOD This study was a retrospective review of patients infected with HCV in childhood enrolled in HCV Research UK. A total of 1,049 patients were identified and included. RESULTS The main routes of infection were intravenous drug use (53%), blood product exposure (24%) and perinatal infection (11%). Liver disease developed in 32% of patients, a median of 33 years after infection, irrespective of the mode of infection. Therefore, patients with perinatal exposure developed cirrhosis at an earlier age than the rest of the risk groups. The incidence of hepatocellular carcinoma (HCC) was 5%, liver transplant 4% and death occurred in 3%. Overall, 663 patients were treated (55% with interferon/pegylated interferon and 40% with direct-acting antivirals). Sustained virological response (SVR) was achieved in 406 (75%). There was a higher mortality rate among patients without SVR vs. those with SVR (5% vs. 1%, p = 0.003). Treatment was more effective in patients without cirrhosis and disease progression was less frequent (13%) than in patients with cirrhosis at the time of therapy (28%) p < 0.001. Patients with cirrhosis were more likely to develop HCC, require liver transplantation, or die. CONCLUSION HCV infection in young people causes significant liver disease, which can now be prevented with antiviral therapy. Early treatment, especially before development of cirrhosis is essential. Detection of HCV should be aimed at relevant risk groups and antiviral therapy should be made available in childhood to prevent long-term liver disease and spread of HCV. LAY SUMMARY Chronic hepatitis C virus (HCV) infection is a global health problem, which can now be treated with potent direct-acting antiviral drugs. This study demonstrates that HCV infection in childhood causes serious liver disease in 32% of patients, a median of 33 years after infection, irrespective of age, mode and route of infection. Disease outcomes were better in patients treated before the development of advanced liver disease. Antiviral therapy should be made available in childhood to prevent long-term liver disease and the spread of HCV.
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Affiliation(s)
- Line Modin
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK.
| | - Adam Arshad
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
| | - Bryony Wilkes
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Jennifer Benselin
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Carla Lloyd
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
| | - William L Irving
- Gastrointestinal and Liver Disorders Team, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and the University of Nottingham, UK
| | - Deirdre A Kelly
- Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK
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18
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Gowda C, Kennedy S, Glover C, Prasad MR, Wang L, Honegger JR. Enhanced identification of maternal hepatitis C virus infection using existing public health surveillance systems. Paediatr Perinat Epidemiol 2018; 32:401-410. [PMID: 29972246 PMCID: PMC6512319 DOI: 10.1111/ppe.12481] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is under-recognized among US adults and children. Prenatal HCV screening may help close the diagnosis gap among women while also identifying at-risk infants. Current surveillance efforts for maternal HCV rely primarily on birth certificate data. We sought a more accurate assessment of HCV prevalence among pregnant women in Ohio by combining existing public health surveillance data. METHODS Vital Statistics (VS) birth certificate data and Ohio Disease Reporting System (ODRS) HCV case data, both available through the Ohio Department of Health, were linked to determine rates of past or present HCV infection among women giving birth from 2012 to 2015 in Ohio, overall and by county. Among women with available test results, the proportion with present HCV infection indicated by detectable viraemia during pregnancy was calculated. RESULTS Birth certificate data identified 4695 deliveries to women with past/present HCV infection during the study period. Linkage to ODRS revealed an additional 1778 deliveries to women with past/present infection, including 355 with confirmed viraemia during pregnancy. The prevalence of past/present HCV among pregnant women in Ohio rose from 0.82% in 2012 to 1.54% in 2015. CONCLUSIONS Maternal HCV infection is under-recognized and increasing in prevalence. Current case identification processes are inadequate in pregnancy, even among women with prior positive HCV testing. Alternative approaches, including enhanced risk factor-based screening or universal prenatal screening in high prevalence settings, are needed to improve rates of HCV recognition among reproductive-aged women and newborns at risk of vertical transmission.
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Affiliation(s)
- Charitha Gowda
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Nationwide Children’s Hospital, Partners for Kids, Columbus, OH, USA
| | - Samuel Kennedy
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Catherine Glover
- The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
| | - Mona R. Prasad
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Ling Wang
- Nationwide Children’s Hospital, Partners for Kids, Columbus, OH, USA
| | - Jonathan R. Honegger
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
- The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
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19
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Affiliation(s)
- Yen H Pham
- Texas Children's Hospital, Baylor College of Medicine, 18200 Katy Freeway, Suite 250, Houston, TX 77094, USA.
| | - Philip Rosenthal
- UCSF Benioff Children's Hospital, University of California San Francisco, 550 16th Street, 5th Floor, San Francisco, CA 94143, USA
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20
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Abstract
PURPOSE OF REVIEW Combined pegylated interferon-α and ribavirin remains the standard therapy for pediatric hepatitis C virus (HCV) infections in 2016, but direct-acting antivirals (DAAs) with greatly improved efficacy and safety are now approved for adults. Here we review the major classes of DAAs and their anticipated use for treatment and potentially prevention of HCV in children. RECENT FINDINGS Currently approved DAAs target the viral protease, polymerase, and NS5A, a protein involved in viral replication and assembly. In combination, DAAs have lifted sustained virologic response rates in adults to more than 90% for multiple HCV genotypes, and the rich DAA pipeline promises further improvements. Clinical trials of interferon-free DAA regimens have been initiated for children ages 3-17 years. In 2016, the first efficacy trial of a preventive HCV vaccine is also underway. While awaiting a vaccine, there is hope that increased DAA utilization may prevent pediatric HCV infections by shrinking the pool of infectious persons. SUMMARY Interferon-free DAA regimens have revolutionized therapy for HCV-infected adults and, pending results of pediatric trials, will likely do the same for HCV-infected children. If widely deployed, DAA therapies may also help to reduce the number of new vertically and horizontally acquired pediatric infections.
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21
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Wen J, Ohmer S, Honegger J. Hepatitis C Virus Infection in Pregnancy and Childhood. HEPATITIS C VIRUS II 2016:187-222. [DOI: 10.1007/978-4-431-56101-9_7] [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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Abstract
Hepatitis C infection is a global health problem. Most infected children have not been identified. Perinatal transmission is the most common mode of acquisition. Liver disease owing to chronic hepatitis C virus (HCV) infection progresses slowly in individuals infected early in life. Serious complications rarely affect patients during childhood. Successful treatment of HCV in adults has improved and recommendations have changed. Treatment in children should be deferred until direct-acting antivirals and interferon-free regimens are available to this population. If treatment cannot be deferred, regimens including peginterferon and ribavirin can be given to children with compensated liver disease.
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Affiliation(s)
- Christine K Lee
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
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23
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Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Marczyńska M. Is liver biopsy still needed in children with chronic viral hepatitis? World J Gastroenterol 2015; 21:12141-12149. [PMID: 26576098 PMCID: PMC4641131 DOI: 10.3748/wjg.v21.i42.12141] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/23/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.
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Abstract
PURPOSE OF REVIEW The global prevalence of hepatitis C infection is increasing. Here, hepatitis C infection in children is reviewed with the assumption that the new effective treatment will be available for treating children. RECENT FINDINGS Recently, effective treatment for hepatitis C infection has become available for adults. Understanding of vertical transmission, how frequently it occurs, which maternal and fetal factors can influence risks is critical in creating these new strategies. The natural history of vertically acquired disease, especially the chance of spontaneous clearance as well as the incidents of rapid progression, needs to be considered in deciding when or if to treat a child. The advantages and drawbacks to delayed treatment (pathophysiologic, psychological, societal, financial) should be considered with respect to the individual child and in a broader context. SUMMARY Although hepatitis C virus infection is not benign, it is usually very slowly progressive and is not easily transmitted through casual contact. With the expectation that effective treatment will soon be available to children, deferring treatment combined with cautious surveillance will optimize hepatitis C virus treatment for children.
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25
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Indolfi G, Guido M, Azzari C, Resti M. Histopathology of hepatitis C in children, a systematic review: implications for treatment. Expert Rev Anti Infect Ther 2015. [PMID: 26202832 DOI: 10.1586/14787210.2015.1070668] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic hepatitis C in children is usually considered a clinically mild and slowly progressive disease. Few pediatric studies focused on histopathology of children with hepatitis C are available. Those available show, overall, a wide spectrum of findings ranging from normal liver to cirrhosis and hepatocellular carcinoma. The present systematic review provides a comprehensive overview of the studies that explored histopathology in children with hepatitis C. Factors affecting the presence and the degree of necroinflammation, fibrosis and steatosis and the risk of progression to advanced liver disease were extensively evaluated. Insights on the possible role of histopathology findings in the decision-making process of whether or not to treat children with hepatitis C are provided.
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Affiliation(s)
- Giuseppe Indolfi
- a 1 Paediatric and Liver Unit Meyer Children's University Hospital of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
| | - Maria Guido
- b 2 Department of Medicine-DIMED, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | - Chiara Azzari
- c 3 Immunology Unit and Laboratory at Meyer Children's University Hospital of Florence and Department of Health Sciences, University of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
| | - Massimo Resti
- a 1 Paediatric and Liver Unit Meyer Children's University Hospital of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
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26
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Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Walewska-Zielecka B, Marczyńska M. The influence of hepatitis B and C virus coinfection on liver histopathology in children. Eur J Pediatr 2015; 174:345-53. [PMID: 25172445 PMCID: PMC4334106 DOI: 10.1007/s00431-014-2402-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Revised: 08/11/2014] [Accepted: 08/13/2014] [Indexed: 12/17/2022]
Abstract
The influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell's modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activity Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- Department of Children's Infectious Diseases, Medical University of Warsaw, ul. Wolska 37, 01-201, Warsaw, Poland,
| | - Barbara Kowalik-Mikołajewska
- Department of Children’s Infectious Diseases, Medical University of Warsaw, ul. Wolska 37, 01-201 Warsaw, Poland ,Warsaw Hospital for Infectious Diseases, Warsaw, Poland
| | - Małgorzata Aniszewska
- Department of Children’s Infectious Diseases, Medical University of Warsaw, ul. Wolska 37, 01-201 Warsaw, Poland ,Warsaw Hospital for Infectious Diseases, Warsaw, Poland
| | | | - Magdalena Marczyńska
- Department of Children’s Infectious Diseases, Medical University of Warsaw, ul. Wolska 37, 01-201 Warsaw, Poland ,Warsaw Hospital for Infectious Diseases, Warsaw, Poland
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27
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Shah U. Infections of the Liver. DISEASES OF THE LIVER IN CHILDREN 2014. [PMCID: PMC7121352 DOI: 10.1007/978-1-4614-9005-0_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
The portal vein carries blood from the gastrointestinal tract to the liver and in so doing carries microbes as well. The liver may therefore be involved in infections with a myriad number of microbial organisms. While some of these infections most commonly occur in the immunocompromised host, others affect the immune competence. Hepatic infections may be primary in nature or secondary, as part of systemic or contagious disease. The purpose of this chapter is to provide a brief overview of the various infections of the liver in the pediatric patient.
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28
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Mohan P, Barton BA, Narkewicz MR, Molleston JP, Gonzalez-Peralta RP, Rosenthal P, Murray KF, Haber B, Schwarz KB, Goodman ZD. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study. Hepatology 2013; 58:1580-6. [PMID: 23703847 PMCID: PMC5493995 DOI: 10.1002/hep.26519] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Accepted: 05/01/2013] [Indexed: 12/13/2022]
Abstract
UNLABELLED Clinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005). CONCLUSION Although in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions.
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Affiliation(s)
- Parvathi Mohan
- Children’s National Medical Center, The George Washington School of Medicine, Washington DC
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29
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Siberry GK, Abzug MJ, Nachman S, Brady MT, Dominguez KL, Handelsman E, Mofenson LM, Nesheim S, National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, American Academy of Pediatrics. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. Pediatr Infect Dis J 2013; 32 Suppl 2:i-KK4. [PMID: 24569199 PMCID: PMC4169043 DOI: 10.1097/01.inf.0000437856.09540.11] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- George K Siberry
- 1National Institutes of Health, Bethesda, Maryland 2University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado 3State University of New York at Stony Brook, Stony Brook, New York 4Nationwide Children's Hospital, Columbus, Ohio 5Centers for Disease Control and Prevention, Atlanta, Georgia
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30
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Abstract
HBV and HCV are the predominant causes of chronic viral hepatitis in children and adults. The main purposes of the present review are to provide the reader with a comprehensive overview of the currently available therapies for chronic hepatitis B and C in children and to critically review the current guidelines and indications for treatment provided by the major international societies and by the consensus of expert panels. Overall, a conservative approach is generally warranted in children with chronic hepatitis B. For HCV, the high effectiveness of pegylated interferon and ribavirin in children with genotype 2 or 3 chronic infection supports the decision to treat. For genotype 1 infection the encouraging results of the use of direct antiviral agents in adults suggest a more conservative approach.
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Affiliation(s)
- Giuseppe Indolfi
- Pediatric & Liver Unit, Meyer Children’s University Hospital of Florence, Viale Pieraccini 34, Firenze, Italy, I-50134
| | - Alessandro Nesi
- Pediatric & Liver Unit, Meyer Children’s University Hospital of Florence, Viale Pieraccini 34, Firenze, Italy, I-50134
| | - Massimo Resti
- Pediatric & Liver Unit, Meyer Children’s University Hospital of Florence, Viale Pieraccini 34, Firenze, Italy, I-50134
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31
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Clinical Picture and Liver Histology of Chronic Hepatitis C in Children. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2012. [DOI: 10.1097/ipc.0b013e3182425b13] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Robinson JL, Doucette K. The natural history of hepatitis C virus infection acquired during childhood. Liver Int 2012; 32:258-70. [PMID: 22098487 DOI: 10.1111/j.1478-3231.2011.02633.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2011] [Accepted: 08/02/2011] [Indexed: 12/23/2022]
Abstract
BACKGROUND The outcome of patients with hepatitis C virus (HCV) infection acquired during childhood in the absence of antiviral therapy is not clear. AIMS The purpose of this study was to review the outcome of untreated HCV acquired in childhood. Only population-based studies were included, as referred cases would be predicted to have more severe disease. METHODS A systematic review of the literature was completed up to October 2010 to identify studies where a population was screened for HCV infection that was presumably acquired during childhood. Demographical and clinical data were collected on infected patients who had not been treated with an antiviral. Primary outcome was development of a severe adverse outcome (cirrhosis, hepatoma, need for a liver transplant or liver-related death). RESULTS There were 25 studies reporting a total of 733 infected patients. Liver biopsy results were provided for 180 patients (25%), revealing cirrhosis in eight (1.0% of the total and 4.0% of those who had a biopsy). None of the other patients developed a severe adverse outcome. As a result of the small number of patients with a severe adverse outcome, risk factors for HCV progression could not be identified. CONCLUSION Although HCV can lead to liver transplantation and death during childhood, the vast majority of patients with disease acquired during childhood have slowly progressive disease. There is no clear indication for antiviral therapy in the majority of children with HCV infection.
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Affiliation(s)
- Joan L Robinson
- Department of Pediatrics, University of Alberta, Edmonton, Canada.
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33
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Spontaneous clearance of hepatitis C virus in vertically infected children. Eur J Pediatr 2012; 171:253-8. [PMID: 21735055 DOI: 10.1007/s00431-011-1517-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Accepted: 06/09/2011] [Indexed: 02/08/2023]
Abstract
UNLABELLED Spontaneous viral clearance of hepatitis C virus (HCV) has been reported to occur in children with vertical HCV infection. However, factors which are associated with or predispose for clearance are largely unknown. In this case series we retrospectively analyzed laboratory parameters associated with spontaneous clearance of HCV in vertically infected children. The charts of six patients with documented spontaneous viral clearance by the age of 5 years were reviewed regarding clinical course, liver function tests (LFTs) and trend of HCV gene copy numbers. Spontaneous viral elimination was observed between the 25th and 52nd months of age. All patients had elevated LFTs, which peaked before 20 months of life. Peak LFT elevation was followed by normalization of LFTs and decline in viral load. These findings suggest that, in vertically HCV-infected children, a potent inflammatory response in the liver precedes viral clearance. Therefore, temporarily elevated LFTs, followed by a decline of viral load may be indicative of a near viral clearance in early childhood. CONCLUSION Further investigations regarding the development of optimal treatment algorithms should take into account factors, which are associated with possible spontaneous viral resolution, such as viral genotype, favourable host factors as well as direct and indirect parameters of antiviral immunity, and the individual course of viral replication.
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Abdel-Hady M, Bunn SK, Sira J, Brown RM, Brundler MA, Davies P, Kelly DA. Chronic hepatitis C in children--review of natural history at a National Centre. J Viral Hepat 2011; 18:e535-40. [PMID: 21914074 DOI: 10.1111/j.1365-2893.2011.01456.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children's Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow-up of 6 months were included. One hundred and thirty-three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired group (9%). Seventy-six had a liver biopsy at diagnosis. There was no evidence of fibrosis in 46%, mild fibrosis in 50% and moderate to severe fibrosis in 4%. None had cirrhosis. There was a statistically significant relationship between fibrosis score and older age at the time of biopsy (P = 0.02) and longer duration of infection (P = 0.05). Eighty children received treatment for HCV. Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of HCV infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis.
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Affiliation(s)
- M Abdel-Hady
- Liver Unit, Birmingham Children's Hospital, Birmingham, UK.
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36
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Management of chronic hepatitis C in childhood: the impact of therapy in the clinical practice during the first 2 decades. Dig Liver Dis 2011; 43:325-9. [PMID: 21111693 DOI: 10.1016/j.dld.2010.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2010] [Revised: 09/28/2010] [Accepted: 10/14/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Treatment of chronic hepatitis C in children is controversial and its role in the clinical practice is unknown. We retrospectively investigated the impact of treatment in a large cohort of children with chronic hepatitis C over the past 20 years. METHODS 376 hepatitis C virus RNA positive children were recruited consecutively in five Italian centres since 1990 and followed for 1-17 years. RESULTS 86 (23%) subjects were treated: 73 with recombinant interferon alone and 13 with pegylated-interferon and ribavirin. Sustained clearance of hepatitis C virus RNA was observed in 25% of the former, in 92% of the latter and in 9% of untreated cases (p < 0.001). Loss of viraemia was recorded in all children with genotype 2-3 and in 6 of 7 with hepatitis C virus genotype 1 treated with combination therapy. At last evaluation 45% of patients were young adults and 15% had cleared viraemia. Overall, 152 (40%) were putative candidates to therapy. CONCLUSIONS Few Italian children with chronic hepatitis C have been treated in the past 20 years. The poor propensity to spontaneous clearance of viraemia and the efficacy of combination therapy should encourage to consider treatment in attempt to shorten the duration of viral replication.
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Karnsakul W, Schwarz KB. Hepatitis. INFECTIOUS DISEASES OF THE FETUS AND NEWBORN 2011:800-813. [DOI: 10.1016/b978-1-4160-6400-8.00025-0] [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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Indolfi G, Bartolini E, Casavola D, Resti M. Chronic hepatitis C virus infection in children and adolescents: Epidemiology, natural history, and assessment of the safety and efficacy of combination therapy. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2010; 1:115-28. [PMID: 24600267 PMCID: PMC3915892 DOI: 10.2147/ahmt.s6750] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) is the most common cause of chronic liver disease of infectious etiology in children. Most of the children infected with HCV are asymptomatic, and only a few of them develop signs and symptoms of end-stage liver disease early in life. It is not possible to predict either in which patients HCV infection will have a bad outcome or the critical time in early adulthood when disease progression will accelerate. The experiences with therapy in children with chronic hepatitis C are based on earlier and continuing data from adult trials. The currently recommended treatment for chronic HCV infection in adults is the combination of peginterferon-á and ribavirin. The choice of this regimen is based on the results of randomized clinical trials that demonstrated the superiority of this combination treatment over standard interferon-á and ribavirin. Recently, results of pivotal, multicenter, interventional open-label studies on combined treatment with peginterferon-á and ribavirin in children have been published, and the US Food and Drug Administration and the European Medicines Agency have approved the combination therapy in those older than 3 years. The aim of this review is to evaluate critically the available data regarding the safety and efficacy of combination treatment with peginterferon-á and ribavirin in children.
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Affiliation(s)
- Giuseppe Indolfi
- Department of Sciences for Women and Child's Health, Liver and Pediatric Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Elisa Bartolini
- Department of Sciences for Women and Child's Health, Liver and Pediatric Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Davide Casavola
- Department of Sciences for Women and Child's Health, Liver and Pediatric Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Massimo Resti
- Department of Sciences for Women and Child's Health, Liver and Pediatric Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy
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El-Shabrawi MH, Mohsen NA, Sherif MM, El-Karaksy HM, Abou-Yosef H, El-Sayed HM, Riad H, Bahaa N, Isa M, El-Hennawy A. Noninvasive assessment of hepatic fibrosis and necroinflammatory activity in Egyptian children with chronic hepatitis C virus infection using FibroTest and ActiTest. Eur J Gastroenterol Hepatol 2010; 22:946-951. [PMID: 20110820 DOI: 10.1097/meg.0b013e328336ec84] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis. Liver biopsy, because of its limitations and risks, might be considered an imperfect gold standard for assessing the severity of chronic liver diseases. In this study, we aimed to prospectively validate FibroTest (FT) and ActiTest (AT) as noninvasive serum biochemical markers for assessment of the degree of hepatic fibrosis and necroinflammatory activity respectively, in pediatric patients with chronic HCV infection and compare them to liver biopsy. METHODS Fifty patients, aged 2 to 18 years, with chronic HCV infection were prospectively enrolled. Two assessments were carried out, within 24-h duration, one of a liver biopsy specimen and the other FT and AT measured in serum sample. FINDINGS A highly significant linear trend and correlation were found between FT-related fibrosis and fibrosis stage by METAVIR scoring on histopathological examination. A highly significant correlation was also found between AT and necroinflammatory histological activity using METAVIR as well. The FT area under the receiver operating characteristic curve (AUROC) is 0.97, SE=0.02 which can diagnose patients with mild stage of fibrosis, thus discriminating them from those with no (or minimal) fibrosis. The AT can successfully discriminate between patients with moderate activity and those with mild activity with AUROC=0.93, SE=0.06. CONCLUSION FT and AT are potential noninvasive methods for assessment of hepatic fibrosis and necroinflammatory activity in pediatric patients with chronic HCV infection in comparison with liver biopsy.
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40
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Liver histology damage in children with chronic hepatitis C. Pediatr Infect Dis J 2010; 29:189-90; author reply 190. [PMID: 20118749 DOI: 10.1097/inf.0b013e3181c11c27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Hepatitis C affects 4-10% of children born to infected mothers, and 80% of them develop chronic infection. Most patients with chronic hepatitis C virus infection are asymptomatic, with persistent or intermittent biochemical abnormalities. Severe liver disease may develop 10 years after onset of infection, with a less than 2% overall risk during the pediatric age. Available therapies have no contraindication in children if otherwise healthy. The US FDA and EMEA have recently approved combined pegylated-IFN-alpha 2b plus ribavirin treatment for children, who should be over 3 years of age in order to avoid severe side effects. Experiences in pilot trials and international studies indicate a response rate of 50% in genotype 1 patients, and more than 90% in genotype 2 or 3 patients, indicating resolution of chronic disease.
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Affiliation(s)
- Paloma Jara
- Servicio de Hepatología, Hospital Infantil Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
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42
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Natural course of HCV infection in childhood cancer survivors. Support Care Cancer 2009; 18:1413-20. [DOI: 10.1007/s00520-009-0763-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2009] [Accepted: 10/12/2009] [Indexed: 02/07/2023]
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43
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Mofenson LM, Brady MT, Danner SP, Dominguez KL, Hazra R, Handelsman E, Havens P, Nesheim S, Read JS, Serchuck L, Van Dyke R. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep 2009; 58:1-166. [PMID: 19730409 PMCID: PMC2821196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2023] Open
Abstract
This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. A separate document about preventing and treating of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists. The guidelines were developed by a panel of specialists in pediatric HIV infection and infectious diseases (the Pediatric Opportunistic Infections Working Group) from the U.S. government and academic institutions. For each OI, a pediatric specialist with content-matter expertise reviewed the literature for new information since the last guidelines were published; they then proposed revised recommendations at a meeting at the National Institutes of Health (NIH) in June 2007. After these presentations and discussions, the guidelines underwent further revision, with review and approval by the Working Group, and final endorsement by NIH, CDC, the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society (PIDS), and the American Academy of Pediatrics (AAP). The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation so readers can ascertain how best to apply the recommendations in their practice environments. An important mode of acquisition of OIs, as well as HIV infection among children, is from their infected mother; HIV-infected women coinfected with opportunistic pathogens might be more likely than women without HIV infection to transmit these infections to their infants. In addition, HIV-infected women or HIV-infected family members coinfected with certain opportunistic pathogens might be more likely to transmit these infections horizontally to their children, resulting in increased likelihood of primary acquisition of such infections in the young child. Therefore, infections with opportunistic pathogens might affect not just HIV-infected infants but also HIV-exposed but uninfected infants who become infected by the pathogen because of transmission from HIV-infected mothers or family members with coinfections. These guidelines for treating OIs in children therefore consider treatment of infections among all children, both HIV-infected and uninfected, born to HIV-infected women. Additionally, HIV infection is increasingly seen among adolescents with perinatal infection now surviving into their teens and among youth with behaviorally acquired HIV infection. Although guidelines for postpubertal adolescents can be found in the adult OI guidelines, drug pharmacokinetics and response to treatment may differ for younger prepubertal or pubertal adolescents. Therefore, these guidelines also apply to treatment of HIV-infected youth who have not yet completed pubertal development. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for preventing and treating OIs, especially those OIs for which no specific therapy exists; 2) information about the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information about managing antiretroviral therapy in children with OIs, including potential drug--drug interactions; 4) new guidance on diagnosing of HIV infection and presumptively excluding HIV infection in infants that affect the need for initiation of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PCP) in neonates; 5) updated immunization recommendations for HIV-exposed and HIV-infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines; 6) addition of sections on aspergillosis; bartonella; human herpes virus-6, -7, and -8; malaria; and progressive multifocal leukodystrophy (PML); and 7) new recommendations on discontinuation of OI prophylaxis after immune reconstitution in children. The report includes six tables pertinent to preventing and treating OIs in children and two figures describing immunization recommendations for children aged 0--6 years and 7--18 years. Because treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents might change therapeutic options and preferences, these recommendations will be periodically updated and will be available at http://AIDSInfo.nih.gov.
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Affiliation(s)
| | | | - Susie P. Danner
- Centers from Disease Control and Prevention, Atlanta, Georgia
| | | | - Rohan Hazra
- National Institutes of Health, Bethesda, Maryland
| | | | - Peter Havens
- Childrens Hospital of Wisconsin, Milwaukee, Wisconsin
| | - Steve Nesheim
- Centers from Disease Control and Prevention, Atlanta, Georgia
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Karnsakul W, Alford MK, Schwarz KB. Managing pediatric hepatitis C: current and emerging treatment options. Ther Clin Risk Manag 2009; 5:651-60. [PMID: 19707281 PMCID: PMC2731021 DOI: 10.2147/tcrm.s5078] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2009] [Indexed: 12/18/2022] Open
Abstract
Since 1992, the maternal–fetal route of transmission has become the dominant route for acquisition of hepatitis C (HCV) infection by children. With increasing knowledge of antiviral treatment for HCV infection, the main goal of therapy is to achieve a sustained virological response (SVR) as defined by undetectable serum HCV RNA by polymerase chain reaction assay six months after cessation of therapy. In young children, interferon therapy is more effective than in adults with chronic HCV infection (CHC). Although children clearly have a milder degree of liver pathology, data have indicated that hepatic inflammation from HCV infection can progress to fibrosis or cirrhosis in children. Hepatocellular carcinoma has been reported in adolescents with CHC. In this article, recent improvements in therapy of children with CHC and in the clinical development of new emerging drugs with potential use in children will be reviewed.
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Affiliation(s)
- Wikrom Karnsakul
- Pediatric Liver Center, Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins School of Medicine, Baltimore, MD, USA
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45
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Henderson WA, Shankar R, Feld JJ, Hadigan CM. Symptomatic and pathophysiologic predictors of hepatitis C virus progression in pediatric patients. Pediatr Infect Dis J 2009; 28:724-7. [PMID: 19593250 PMCID: PMC2990981 DOI: 10.1097/inf.0b013e31819f1f71] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND The slow progression of hepatitis C virus (HCV) infection could ultimately negatively impact pediatric patients during their lifespan. This study describes the symptomatic and pathophysiologic presentation of HCV infection in a cohort of pediatric outpatients. METHODS HCV-positive patients were identified by diagnosis codes from outpatient visits. Demographic and pathophysiologic indicators (comorbidities, reported symptoms, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV viral load, genotype, and liver biopsy results) were collected and analyzed. RESULTS We reviewed 62 patients with HCV infection who were from 3 months and 19 years of age (M +/- SD, 12.5 +/- 5.8 years). Sixty percent presented with clinical symptoms of fatigue, joint-abdominal pain, bruising/bleeding, or other non-specific symptoms. On liver biopsy (n = 35) 80% had evidence of inflammation, 57% had fibrosis, and 9% had steatosis. All patients with steatosis or cirrhosis reported symptoms. Males were significantly more likely than women to be symptomatic (58.3% vs. 41.7%, P = 0.04). Patients with symptoms were significantly older (M = 13.5 +/- 5.2 vs. 8.9 +/- 5.5 years, P = 0.003). There was a significant inverse relationship between viral load and symptoms (chi = 4.75, P = 0.03). Patients with low viral load (<2 million copies) were 5 times more likely to have symptoms than those with high viral loads (P = 0.03). Significance was also noted between HCV genotype and ALT levels (chi = 3.72, P = 0.05). There were no significant relationships between symptom status and race, comorbidities, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV genotype, or liver histology. CONCLUSION Pediatric patients with HCV can have significant symptoms and physiologic liver changes related to HCV.
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Affiliation(s)
- Wendy A Henderson
- Biobehavioral Unit, Symptoms Management Branch, Intramural Research Program, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA.
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47
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Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335-74. [PMID: 19330875 PMCID: PMC7477893 DOI: 10.1002/hep.22759] [Citation(s) in RCA: 2237] [Impact Index Per Article: 139.8] [Reference Citation Analysis] [Collaborators] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Marc G Ghany
- Department of Health and Human Services, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Collaborators
Margaret C Shuhart, Gary L Davis, Kiran Bambha, Andres Cardenas, Timothy J Davern, José Franco, Steven-Huy B Han, Stephen A Harrison, Charles D Howell, Simon C Ling, Lawrence U Liu, Paul Martin, Robert S O'Shea, Nancy Reau, Bruce A Runyon, Jayant A Talwalkar, John B Wong, Colina Yim,
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48
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Rodrigue JR, Balistreri W, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Schwarz KB, Robuck P, Barton B, González-Peralta RP. Impact of hepatitis C virus infection on children and their caregivers: quality of life, cognitive, and emotional outcomes. J Pediatr Gastroenterol Nutr 2009; 48:341-7. [PMID: 19242286 PMCID: PMC2649743 DOI: 10.1097/mpg.0b013e318185998f] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Hepatitis C virus (HCV) infection is associated with decreased quality of life (QOL) and neurocognitive dysfunction in adults, but little is known about its impact on children and their caregivers. PATIENTS AND METHODS We studied the QOL, behavioral, emotional, and cognitive functioning of 114 treatment-naïve children with HCV enrolled in a placebo-controlled, randomized, multisite clinical trial evaluating peginterferon alpha-2a alone or with ribavirin. Baseline assessment included measures of children's QOL, cognitive functioning, behavioral adaptation, and depression. Caregivers' QOL also was assessed. RESULTS Relative to published normative data, caregivers were more likely to believe that their children's health was poor and would likely worsen (t = 3.93; P < 0.0001), and reported higher concern about their children's health status (t = 6.63; P < 0.0001) and that this concern limited family activities (t = 2.45; P < 0.01); they also viewed their children as having more internalizing behavioral problems (t = 1.98; P < 0.05). Only 2 (2%) children had a score in the clinically depressed range. Children with HCV had worse cognitive functioning than the normative sample but significantly better functioning than children with attention-deficit/hyperactivity disorder. Caregivers' QOL scores did not differ significantly from the normative sample, but infected mothers had lower QOL than noninfected caregivers. Caregivers were highly distressed about their children's medical circumstances. CONCLUSIONS Although HCV infection, in its early stages, does not lead to global impairment in QOL, cognitive, behavioral, or emotional functioning in children, it is associated with higher caregiver stress and strain on the family system, and it may be associated with some cognitive changes in children.
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Affiliation(s)
- James R Rodrigue
- The Transplant Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
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Sequential antiviral and iron chelation treatment in a teenage boy with congenital anemia, chronic hepatitis C, and secondary hemosiderosis. J Pediatr Gastroenterol Nutr 2009; 48:382-5. [PMID: 19274798 DOI: 10.1097/mpg.0b013e3181602190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Abstract
In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.
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Affiliation(s)
- Leonard B Seeff
- National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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