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Nwaohiri A, Schillie S, Bulterys M, Kourtis AP. Hepatitis C virus infection in children: How do we prevent it and how do we treat it? Expert Rev Anti Infect Ther 2018; 16:689-694. [PMID: 30091654 DOI: 10.1080/14787210.2018.1509707] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important contributor to the worldwide burden of liver-related morbidity and mortality. Mother-to-child transmission of HCV ranges from 6 to 11% in different populations globally, but accurate estimates on the burden of pediatric HCV infection are limited because screening approaches are not consistent. Areas covered: The advent of new direct-acting antiviral agents that achieve very high rates of sustained virologic response (representing virologic cure) with short (i.e. 8-12 weeks) regimens has revolutionized the field of HCV treatment and led to the development of global elimination goals for HCV transmission and mortality. However, information on their safety during pregnancy and efficacy in preventing mother-to-child transmission is lacking. Currently, there are no approved treatment regimens with these antiviral agents for children younger than 12 years of age. Expert commentary: If these agents are shown to be safe during pregnancy and effective in preventing transmission to the infant, screening of pregnant women and antenatal treatment of those infected, could pave the way for eliminating pediatric HCV infection- particularly as these drugs become less costly and more accessible. Treatment of infected children when indicated, along with universal safe health care practices, can further pediatric HCV elimination.
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Affiliation(s)
- Anuli Nwaohiri
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Sarah Schillie
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Marc Bulterys
- b Division of Viral Hepatitis , National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention , Atlanta , GA , USA
| | - Athena P Kourtis
- a Division of Reproductive Health , National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta , GA , USA
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Treatment of Hepatitis C during Pregnancy-Weighing the Risks and Benefits in Contrast to HIV. Curr HIV/AIDS Rep 2018; 15:155-161. [DOI: 10.1007/s11904-018-0386-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
Chronic viral hepatitis is a global health threat and financial burden. Hepatitis B and C viruses (HBV and HCV) are the most common causes of chronic viral hepatitis in the United States. Most cases are asymptomatic before adulthood. Research has resulted in effective therapy for HCV and the promise of effective therapies for HBV. For HCV, therapy is pegylated interferon and ribavirin. Clinical trials with effective direct-acting antiviral agents are underway in pediatrics. For HBV, approved agents are alpha-interferon, lamivudine, adefovir, tenofovir, and entecavir. However, treatment seldom results in functional cure and more effective therapies are urgently needed.
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Affiliation(s)
- Wikrom Karnsakul
- Pediatric Liver Center, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA.
| | - Kathleen B Schwarz
- Professor, Pediatric Liver Center, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Squires JE, Balistreri WF. Hepatitis C virus infection in children and adolescents. Hepatol Commun 2017; 1:87-98. [PMID: 29404447 PMCID: PMC5721428 DOI: 10.1002/hep4.1028] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/17/2017] [Accepted: 02/22/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center Pittsburgh PA
| | - William F Balistreri
- Division of Gastroenterology Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati OH
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Eke CB, Ogbodo SO, Ukoha OM, Muoneke VU, Ibekwe RC, Ikefuna AN. Seroprevalence and Correlates of Hepatitis C Virus Infection in Secondary School Children in Enugu, Nigeria. Ann Med Health Sci Res 2016; 6:156-61. [PMID: 27398246 PMCID: PMC4924488 DOI: 10.4103/2141-9248.183940] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Although children comprise a small fraction of the burden of hepatitis C virus (HCV) infections, which is a major global health challenge, a significant number of them develop chronic HCV infection and are at risk of its complications. AIM The aim of the current study was to determine the prevalence and associated factors of HCV infection in school children in Enugu urban. SUBJECTS AND METHODS This was a cross-sectional seroepidemiological study involving children aged 10-18 years selected using multistage systematic sampling in Enugu metropolis, Southeast Nigeria. The anti-HCV was tested using a 3(rd) generation enzyme-linked immunosorbent assay. Data were analyzed using SPSS Version 16.0 with the level of significance set at P < 0.05. RESULTS Four hundred and twenty children were selected and screened comprising 210 (50.0%) males and females. The seroprevalence of anti-HCV was 4 (1.0%). Three (75%) out of the four positive cases for the anti-HCV were females while one was a male giving a male to female ratio of 0.3-1. Traditional scarifications/tattoos were the putative risk factors observed to be significantly associated with anti-HCV seropositivity. CONCLUSION This study has demonstrated an anti-HCV seroprevalence of 1.0% among children aged 10-18 years in Enugu with traditional scarification as the predominant associated risk factor. Proper health education including school health education and promotion of behavioral change among the public on the practice of safe scarifications/tattoos should be encouraged in our setting.
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Affiliation(s)
- CB Eke
- Department of Pediatrics, College of Medicine, University of Nigeria, Enugu, Nigeria
| | - SO Ogbodo
- Department of Biochemistry, College of Medicine, Enugu State University of Science and Technology Teaching Hospital, Enugu, Nigeria
| | - OM Ukoha
- Department of Pediatrics, Enugu State University of Science and Technology Teaching Hospital, Enugu, Nigeria
| | - VU Muoneke
- Department of Pediatrics, College of Medicine, University of Nigeria, Enugu, Nigeria
| | - RC Ibekwe
- Department of Pediatrics, College of Medicine, University of Nigeria, Enugu, Nigeria
| | - AN Ikefuna
- Department of Pediatrics, College of Medicine, University of Nigeria, Enugu, Nigeria
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Tosone G, Maraolo AE, Mascolo S, Palmiero G, Tambaro O, Orlando R. Vertical hepatitis C virus transmission: Main questions and answers. World J Hepatol 2014; 6:538-548. [PMID: 25232447 PMCID: PMC4163737 DOI: 10.4254/wjh.v6.i8.538] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.
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Garazzino S, Calitri C, Versace A, Alfarano A, Scolfaro C, Bertaina C, Vatrano S, Mignone F, Licciardi F, Gabiano C, Tovo PA. Natural history of vertically acquired HCV infection and associated autoimmune phenomena. Eur J Pediatr 2014; 173:1025-31. [PMID: 24585099 DOI: 10.1007/s00431-014-2286-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Revised: 02/10/2014] [Accepted: 02/16/2014] [Indexed: 12/17/2022]
Abstract
UNLABELLED The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. CONCLUSIONS Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.
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Affiliation(s)
- Silvia Garazzino
- Department of Pediatrics, University of Turin, Regina Margherita Children's Hospital, Turin, Italy,
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Low prevalence of hepatitis B and C virus markers among children and adolescents. BIOMED RESEARCH INTERNATIONAL 2014; 2014:324638. [PMID: 25093164 PMCID: PMC4100382 DOI: 10.1155/2014/324638] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 05/22/2014] [Accepted: 05/27/2014] [Indexed: 12/11/2022]
Abstract
This study aimed to determine the prevalence of HBV and HCV among children and adolescents attending schools and daycare centres in Rio de Janeiro State, located in southern Brazil. Serum samples from 1,217 individuals aged 0 to 18 years were collected from 1999 to 2012 and tested for HBsAg, total anti-HBc, anti-HBs, and anti-HCV by ELISA. Reactive HBsAg and anti-HBc samples were tested for HBV DNA. Reactive anti-HCV samples were tested for HCV RNA and genotyped by RFLP. HBsAg was detected in 1.8% of individuals, and total anti-HBc was detected among 3.6% of individuals. Anti-HBs reactivity was found among 25.3% (322/1,217) of the individuals and increased from 6.28% in the years 1999-2000 to 76.2% in the years 2001–2012 (P < 0.0001). HBV DNA was detected in 18 of 51 individuals who presented with HBsAg or isolated anti-HBc, and nine were considered occult hepatitis B cases. Three individuals were anti-HCV- and HCV RNA-positive: two of them were infected with genotype 1, and the other was infected with genotype 3. Low levels of HBV and HCV markers were observed in children and adolescents. HBV immunity increased during the period of study, indicating that childhood universal HBV vaccination has been effective for controlling HBV infection in Brazil.
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Kamal SM. Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents. Hepat Med 2014; 6:61-77. [PMID: 25114601 PMCID: PMC4075960 DOI: 10.2147/hmer.s41127] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world’s population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.
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Affiliation(s)
- Sanaa M Kamal
- Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt ; Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi Arabia
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Farghaly HS, Metwalley KA, El-Hafeez HAA. Hepatitis C virus infection in Egyptian children with type 1 diabetes mellitus: A single center study. Indian J Endocrinol Metab 2014; 18:197-201. [PMID: 24741516 PMCID: PMC3987270 DOI: 10.4103/2230-8210.129111] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Only few studies have evaluated the epidemiology and risk factors of hepatitis C virus (HCV) infection in Egyptian children with type 1 diabetes mellitus (T1DM). The present study aimed at measurement of the rates of anti-HCV positivity by Enzyme-Linked Immuno-Sorbent Assay (ELISA) test and of HCV-Ribonucleic acid (RNA) positivity by polymerase chain reaction (PCR) among children with T1DM and to study the possible risk factors of infection. SETTINGS AND DESIGN Cross-sectional controlled study. MATERIALS AND METHODS The study included 150 children with T1DM (Group 1) (mean age 14. 76 ± 6.4 years). Fifty children age and sex-matched were included as control group (Group 2) (mean age 13.62 ± 2.11 years). They were screened for HCV antibodies using third generation ELISA and HCV-RNA positivity by PCR. RESULTS The frequency of anti-HCV positivity by ELISA was significantly higher in children with T1DM (n = 150) in comparison wiith control group (n = 50) (12% vs 6%; P<0.001), while the frequency of HCV-RNA positivity by PCR among the cases testing positive by ELISA was 75% for both diabetic group and control group. There were no significant differences in serum levels of liver biochemical profile in diabetic children with anti-HCV positivity (n = 18) in comparison to those with anti-HCV negativity (n = 132). Residence in rural area, low socioeconomic class and prior hospitalization were significant risk factors for anti-HCV positivity by ELISA. CONCLUSIONS The frequency of HCV infection in children with T1DM in Upper Egypt appears to be high and is mainly related to residence in rural area, low socioeconomic class and prior hospitalization. HCV infection in these children is not associated with significant changes in hepatic biochemical parameters. RECOMMENDATIONS Implementation of strict infection control measures are highly recommended to reduce the frequency of HCV infection. Furthermore, the silent evolution of HCV infection in children makes periodic screening of HCV in diabetic children mandatory.
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Affiliation(s)
- Hekma Saad Farghaly
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
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Roy A, Lieb W, Garrett B, Hodik M, Klipsch A, Young M, Barton B, Schwarz KB. Recruitment and retention strategies in a clinical trial for children with chronic hepatitis C infection. J Pediatr Nurs 2013; 28:243-8. [PMID: 22999994 PMCID: PMC3540171 DOI: 10.1016/j.pedn.2012.08.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Revised: 08/14/2012] [Accepted: 08/16/2012] [Indexed: 02/06/2023]
Abstract
Successful strategies for recruitment and retention (R & R) in pediatric trials are needed. The purpose of our study was to analyze the effectiveness of R&R in a trial for children with hepatitis C. Recruitment strategies were (1) Initial (months 0-12) and (2) extra effort (months 13-18). Initial strategies enrolled 70/114 (61%) of patients. Extra effort strategies included: (1) radio broadcasts, (2) contact with adult hepatologists, (3) dissemination of study material and (4) modification of the exclusion criteria. The overall retention rate was 84% at 2 years. Lessons learned will be valuable in designing future pediatric trials.
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Affiliation(s)
- Aparna Roy
- Johns Hopkins Medical Institutions, Baltimore, MD, USA
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Le Campion A, Larouche A, Fauteux-Daniel S, Soudeyns H. Pathogenesis of hepatitis C during pregnancy and childhood. Viruses 2012; 4:3531-50. [PMID: 23223189 PMCID: PMC3528278 DOI: 10.3390/v4123531] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 11/18/2012] [Accepted: 11/28/2012] [Indexed: 12/13/2022] Open
Abstract
The worldwide prevalence of HCV infection is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Yet the pathogenesis of hepatitis C during pregnancy and in the neonatal period remains poorly understood. Mother-to-child transmission (MTCT), a leading cause of pediatric HCV infection, takes place at a rate of <10%. Factors that increase the risk of MTCT include high maternal HCV viral load and coinfection with HIV-1 but, intriguingly, not breastfeeding and mode of delivery. Pharmacological prevention of MTCT is not possible at the present time because both pegylated interferon alfa and ribavirin are contraindicated for use in pregnancy and during the neonatal period. However, this may change with the recent introduction of direct acting antiviral agents. This review summarizes what is currently known about HCV infection during pregnancy and childhood. Particular emphasis is placed on how pregnancy-associated immune modulation may influence the progression of HCV disease and impact MTCT, and on the differential evolution of perinatally acquired HCV infection in children. Taken together, these developments provide insights into the pathogenesis of hepatitis C and may inform strategies to prevent the transmission of HCV from mother to child.
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Affiliation(s)
- Armelle Le Campion
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
| | - Ariane Larouche
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Sébastien Fauteux-Daniel
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
| | - Hugo Soudeyns
- Unité d’immunopathologie virale, Centre de recherche du CHU Sainte-Justine, 3175 Côte Sainte-Catherine, local 6735, Montreal, Quebec, H3T 1C5, Canada; E-Mails: (A.L.C); (A.L.); (S.F.-D.)
- Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
- Department of Pediatrics, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, H3C 3J7, Canada
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Velmishi V, Dervishi E, Cullufi P, Bali D, Durro V. Treatment and follow up of children with chronic hepatitis C in Albania. Virol J 2012; 9:17. [PMID: 22244498 PMCID: PMC3271956 DOI: 10.1186/1743-422x-9-17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Accepted: 01/13/2012] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. PATIENTS AND METHODS This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. RESULTS At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% CONCLUSION The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained.
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Affiliation(s)
- Virtut Velmishi
- Service of Pediatric Gastrohepatology, University Hospital Center "Mother Theresa", Rruga "Dibres" No. 372, Tirana, Albania
| | - Ermira Dervishi
- Service of Pediatric Gastrohepatology, University Hospital Center "Mother Theresa", Rruga "Dibres" No. 372, Tirana, Albania
| | - Paskal Cullufi
- Service of Pediatric Gastrohepatology, University Hospital Center "Mother Theresa", Rruga "Dibres" No. 372, Tirana, Albania
| | - Donjeta Bali
- Service of Pediatric Oncohematology, University Hospital Center "Mother Theresa", Rruga "Dibres" No. 372, Tirana, Albania
| | - Vjollca Durro
- Hospital Planning Directory, Ministry of Health, Bulevardi " Bajram Curri", no 1, Tirana, Albania
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Figlerowicz M, Jackowiak P, Formanowicz P, Kędziora P, Alejska M, Malinowska N, Błażewicz J, Figlerowicz M. Hepatitis C virus quasispecies in chronically infected children subjected to interferon-ribavirin therapy. Arch Virol 2010; 155:1977-87. [PMID: 20842394 PMCID: PMC2982956 DOI: 10.1007/s00705-010-0789-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2010] [Accepted: 08/27/2010] [Indexed: 01/30/2023]
Abstract
Accumulating evidence suggests that certain features of hepatitis C virus (HCV), especially its high genetic variability, might be responsible for the low efficiency of anti-HCV treatment. Here, we present a bioinformatic analysis of HCV-1a populations isolated from 23 children with chronic hepatitis C (CHC) subjected to interferon-ribavirin therapy. The structures of the viral quasispecies were established based on a 132-amino-acid sequence derived from E1/E2 protein, including hypervariable region 1 (HVR1). Two types of HCV populations were identified. The first type, found in non-responders, contained a small number of closely related variants. The second type, characteristic for sustained responders, was composed of a large number of distantly associated equal-rank variants. Comparison of 445 HVR1 sequences showed that a significant number of variants present in non-responding patients are closely related, suggesting that certain, still unidentified properties of the pathogen may be key factors determining the result of CHC treatment.
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Affiliation(s)
- Magdalena Figlerowicz
- Department of Infectious Diseases and Child Neurology, Karol Marcinkowski University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland
| | - Paulina Jackowiak
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
| | - Piotr Formanowicz
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
- Institute of Computing Science, Poznań University of Technology, Piotrowo 3A, 60-965 Poznań, Poland
| | - Paweł Kędziora
- Institute of Computing Science, Poznań University of Technology, Piotrowo 3A, 60-965 Poznań, Poland
| | - Magdalena Alejska
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
| | - Nelli Malinowska
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
| | - Jacek Błażewicz
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
- Institute of Computing Science, Poznań University of Technology, Piotrowo 3A, 60-965 Poznań, Poland
| | - Marek Figlerowicz
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland
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Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads. PLoS One 2010. [PMID: 20814429 DOI: 10.1371/journal.pone.0012232.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.
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Waasdorp Hurtado C, Golden-Mason L, Brocato M, Krull M, Narkewicz MR, Rosen HR. Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads. PLoS One 2010; 5:e12232. [PMID: 20814429 PMCID: PMC2923602 DOI: 10.1371/journal.pone.0012232] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2010] [Accepted: 07/24/2010] [Indexed: 12/24/2022] Open
Abstract
Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in ∼80% of cases following exposure, the rate of mother-to-child transmission (2–6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and γδ-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.
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Affiliation(s)
- Christine Waasdorp Hurtado
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Digestive Health Institute, University of Colorado School of Medicine, The Children's Hospital, Aurora, Colorado, United States of America
| | - Lucy Golden-Mason
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, Colorado, United States of America
- Integrated Program in Immunology, University of Colorado and National Jewish Hospital, Denver, Colorado, United States of America
| | - Megan Brocato
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, Colorado, United States of America
| | - Mona Krull
- Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, Colorado, United States of America
| | - Michael R. Narkewicz
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Digestive Health Institute, University of Colorado School of Medicine, The Children's Hospital, Aurora, Colorado, United States of America
| | - Hugo R. Rosen
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, Colorado, United States of America
- Integrated Program in Immunology, University of Colorado and National Jewish Hospital, Denver, Colorado, United States of America
- * E-mail:
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Hurtado CW, Golden-Mason L, Brocato M, Krull M, Narkewicz MR, Rosen HR. Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads. PLoS One 2010. [PMID: 20814429 DOI: 10.1371/journal.pone.001223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.
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Affiliation(s)
- Christine Waasdorp Hurtado
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Digestive Health Institute, University of Colorado School of Medicine, The Children's Hospital, Aurora, Colorado, United States of America
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Danish FA, Koul SS, Subhani FR, Rabbani AE, Yasmin S. Managing HCV infection in pediatric age group: suggested recommendations. Saudi J Gastroenterol 2010; 16:230-5. [PMID: 20616426 PMCID: PMC3003210 DOI: 10.4103/1319-3767.65182] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Hepatitis C virus (HCV) infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.
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Affiliation(s)
- Fazal A. Danish
- Princess of Wales Hospital, Coity Road, Bridgend, United Kingdom CF31 1RQ,Address for correspondence: Dr. Fazal A. Danish, Registrar Gastroenterology, Princess of Wales Hospital, Coity Road, Bridgend, CF31 1RQ, United Kingdom. E-mail:
| | - Salman S. Koul
- Department of Medicine (Unit-I), Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan
| | - Fazal R. Subhani
- Department of Pediatrics, Holy Family Hospital, Rawalpindi, Pakistan
| | - Ahmed E. Rabbani
- Foundation University Medical College (FUMC), Rawalpindi, Pakistan
| | - Saeeda Yasmin
- Department of Surgery, Shifa Hospital, Islamabad, Pakistan
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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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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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Bethlen S, Chandrikakumari K, Leval LD, Giot JB, Mukeba D, Leonard P, Frippiat F, Meuris C, Delwaide J, Moutschen M. Chronic hepatitis C infection in a patient with bone marrow hypoplasia. World J Gastroenterol 2008; 14:4238-40. [PMID: 18636673 PMCID: PMC2725389 DOI: 10.3748/wjg.14.4238] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglobulinemia which is strongly related to B-cell lymphoproliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year-old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid arthritis on account of her diffuse joint pain and inflammation, elevated rheumatoid factor (RF) and Raynaud’s phenomenon. Twenty years later, monoclonal gammopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examination. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lymphoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.
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Abstract
INTRODUCTION The annual incidence of acute hepatitis C virus (HCV) has fallen in recent years, primarily because of effective blood screening efforts and increased education on the dangers of needle sharing. However, hepatitis C infection is still relatively frequent in certain populations. Most patients infected with HCV are unaware of their exposure and remain asymptomatic during the initial stages of the infection, making early diagnosis during the acute phase (first 6 months after infection) unlikely. While some of those infections will have a spontaneous resolution, the majority will progress to chronic HCV. We scanned the literature for predictors of spontaneous resolution and treatment during the acute stage of HCV to identify factors that would assist in treatment decision making. METHODS A medical literature search through MEDLINE was conducted using the keyword "acute hepatitis C" with a variety of keywords focused on (a) epidemiology, (b) natural history and outcome, (c) diagnosis, (d) mode of transmission, and (e) treatment. RESULTS There are no reliable predictors for spontaneous resolution of HCV infection and a significant percentage of individuals exposed to HCV develop persistent infections that progress to chronic liver disease. An intriguing approach is to treat acute HCV and prevent the development of chronic hepatitis. Several clinical trials showed that treatment of hepatitis C infection during the acute phase is associated with high sustained virological response (SVR) rates ranging between 75% and 100%. Although there is a prevailing consensus that intervention during the acute phase is associated with improved viral eradication, relevant clinical questions have remained unanswered by clinical trials. Optimization of therapy for acute hepatitis C infection and identification of predictors of SVR represent a real challenge. CONCLUSION With more than 170 million chronic hepatitis C patients worldwide and an increase in the related morbidity and mortality projected for the next decade, an improvement in our ability to diagnose and treat patients with acute hepatitis C would have a significant impact on the prevalence of chronic hepatitis and its associated complications particularly in countries with a high endemic background of the infection.
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Affiliation(s)
- Sanaa M Kamal
- Department of Gastroenterology and Liver Disease, Ain Shams Faculty of Medicine, Cairo, Egypt
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23
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Rizzetto M, Zoulim F. Viral Hepatitis. TEXTBOOK OF HEPATOLOGY 2007:819-956. [DOI: 10.1002/9780470691861.ch9a] [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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Abstract
Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co-infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.
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Affiliation(s)
- Kilian Weigand
- University of Heidelberg, Department of Gastroenterology, Im Neuenheimer Feld 410, Hei-delberg D-69120, Germany
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25
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Posthouwer D, Fischer K, van Erpecum KJ, Mauser-Bunschoten EP. The natural history of childhood-acquired hepatitis C infection in patients with inherited bleeding disorders. Transfusion 2006; 46:1360-6. [PMID: 16934072 DOI: 10.1111/j.1537-2995.2006.00903.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Although many patients with inherited bleeding disorders have been infected with hepatitis C in early childhood, the natural history of infection in this patient group remains poorly defined. STUDY DESIGN AND METHODS A total of 212 patients with inherited bleeding disorders born between 1976 and 1992 were evaluated for hepatitis C virus (HCV) infection, spontaneous clearance, and (by noninvasive tests) progressive liver disease. RESULTS A total of 120 of 212 patients had been exposed to non-HCV-inactivated clotting products, and 68 of these 120 patients (57%) were anti-HCV-positive. Of these patients, 44 (65%) had chronic hepatitis C (HCV RNA-positive) and 24 (35%) showed spontaneous clearance (HCV RNA-negative). Five patients with hepatitis C were coinfected with hepatitis B virus and/or human immunodeficiency virus (HIV). Multivariate analysis indicated that hepatitis C infection was independently associated with longer treatment period (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9) and exposure to a larger number of donors (OR, 2.1; 95% CI, 1.1-3.9). Spontaneous HCV clearance was associated with a younger age at first exposure to clotting product (p = 0.02). After a mean infection period of 21 years, evidence of cirrhosis was present in 2 patients (5%), both of whom were coinfected with HIV. CONCLUSION Spontaneous HCV clearance is associated with young age at infection. Despite frequent childhood-acquired hepatitis C infection among patients with inherited bleeding disorders, progression to cirrhosis after 21 years of infection is rare. The diagnosis of cirrhosis without biopsy, however, remains challenging in this population, and new, noninvasive means must be developed to accurately identify cirrhotic patients.
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Affiliation(s)
- Dirk Posthouwer
- Van Creveldkliniek, the Julius Center for Health Sciences and Primary Care, and the Department of Gastroenterology, University Medical Center, Utrecht, the Netherlands.
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Sharara AI, Aoun E, Koussa S, Inati A, Taher A. Treatment of acute hepatitis C in a child with thalassemia major using weight-based peginterferon alpha-2b. J Gastroenterol Hepatol 2006; 21:1221. [PMID: 16824084 DOI: 10.1111/j.1440-1746.2006.04174.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Iorio R, Spagnuolo MI. Re: Possible prevention of fulminant hepatic failure in four children with acute severe hepatitis. J Gastroenterol 2005; 40:912-913. [PMID: 16211350 DOI: 10.1007/s00535-004-1656-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2004] [Accepted: 11/26/2004] [Indexed: 02/04/2023]
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Posthouwer D, Wolters VM, Fischer K, Houwen RHJ, van den Berg HM, Mauser-Bunschoten EP. Hepatitis C infection in children with haemophilia: a pilot study. Haemophilia 2004; 10:722-6. [PMID: 15569167 DOI: 10.1111/j.1365-2516.2004.01038.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Many haemophilia patients were infected with hepatitis C virus (HCV) in childhood after transfusion with inadequately or non-virus inactivated clotting factor products. Limited information is available on the clinical course of HCV infection in children. To assess the clinical consequences of hepatitis C in these young patients we performed a pilot study of 31 patients with haemophilia, infected with HCV before the age of 13. Current median age was 20 years. Nineteen (61%) patients had chronic hepatitis C, whereas the remaining 12 patients spontaneously cleared HCV. The median duration of infection was 17 years. Among patients chronically infected with HCV, an enlarged liver and/or spleen on ultrasound was present in 59%, whereas 63% had abnormal aminotransferases and/or gamma-GT values. In conclusion, 39% of the patients infected in childhood cleared HCV spontaneously. The majority of the patients with chronic hepatitis C had ultrasound and/or laboratory abnormalities and these findings may be associated with the presence of chronic liver disease.
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Affiliation(s)
- D Posthouwer
- Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
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El-Raziky MS, El-Hawary M, El-Koofy N, Okasha S, Kotb M, Salama K, Esmat G, El-Raziky M, Abouzied AM, El-Karaksy H. Hepatitis C virus infection in Egyptian children: single centre experience. J Viral Hepat 2004; 11:471-476. [PMID: 15357655 DOI: 10.1111/j.1365-2893.2004.00535.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti-HCV). The data of 105 anti-HCV-positive children presenting to the Pediatric Hepatology Unit, Cairo University Children's Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy-four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3-22 years, with a mean of 11.2 +/- 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti-HBc) were detected in 18 patients (24.3%). Twenty-six of the 43 HCV RNA-positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA-positive cases.
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Affiliation(s)
- M S El-Raziky
- Department of Pediatrics, Cairo University, Cairo, Egypt.
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Gismondi MI, Turazza EI, Grinstein S, Galoppo MC, Preciado MV. Hepatitis C virus infection in infants and children from Argentina. J Clin Microbiol 2004; 42:1199-202. [PMID: 15004075 PMCID: PMC356814 DOI: 10.1128/jcm.42.3.1199-1202.2004] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection is uncommon in children, and its natural history is still unknown. Our aim was to analyze exposure to HCV in 48 infants and children in Argentina and to evaluate consecutive samples in 26 of them to study the outcome of HCV infection in early stages. HCV viremia, as determined by reverse transcription-PCR (RT-PCR) from the 5' untranslated region, showed continuously positive, occasionally positive, and negative patterns during follow-up. Restriction fragment length polymorphism was performed on RT-PCR-positive samples to evaluate HCV genotype. Genotype 1 turned out to be predominant, and no patient displayed a genotype shift during the observation period. Perinatal HCV infection was predominantly observed in patients born to mothers coinfected with HCV and human immunodeficiency virus. HCV viral load was detected by means of the AMPLICOR MONITOR, version 2.0, kit. No correlation was observed between HCV viral load and alanine aminotransferase and aspartate aminotransferase levels, although we detected a trend towards higher levels among patients displaying consecutive positive HCV RT-PCR results. Our results demonstrate that pediatric HCV infection is characterized by high viral loads and diverse HCV viremia patterns, independent of both age and route of transmission in the population under study. Further research is necessary to determine whether the high rate of HCV replication is related to virus variability or to host immune response.
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Affiliation(s)
- María Inés Gismondi
- Laboratorio de Virología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Ciudad de Buenos Aires, Argentina.
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Abstract
The present paper provides a review of the current literature regarding the molecular-based epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV), which are very important viruses underlying the etiology of blood-borne infectious diseases worldwide. Particularly, both HBV and HCV are widespread on the Asian continent and are associated with acute and chronic liver diseases, including hepatocellular carcinoma. HBV has been classified into genotypes A through G and shown to have a distinct geographic distribution. In Asia, genotypes B and C of HBV prevail, and genotype C has been shown to cause more serious liver disease than genotype B. High prevalence of HBV mutants with various forms, such as the pre-S mutant, basal core promoter mutant, YMDD motif mutant and vaccine escape mutant, were seen in Asia and these were found to be related to the severity of liver disease and sensitivity to therapy. HCV has also been classified into multiple genotypes and associated with geographic distribution. HCV genotype 1 is less sensitive to interferon therapy and may be associated with the presence of more serious liver disease than the other genotypes. Data on the relation among the HBV/HCV genotypes, their pathogenicity in chronic liver diseases including hepatocellular carcinoma and their effect on therapy are awaited with great interest, especially in Asia, which is an endemic region of blood-borne hepatitis viruses.
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Affiliation(s)
- Tran T T Huy
- Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan
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