Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children

Abstract

Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.

Zussamenfassung

Chronische Hepatitis C (CHC) stellt eine globale Gesundheitsbelastung dar. Die Mutter-Kind-Übertragung (MTCT) ist für die meisten HCV-Infektionen bei pädiatrischen Patienten verantwortlich. Eine spontane Virusfreisetzung kann in der frühen Kindheit auftreten, ist danach aber selten. In der Regel verläuft die Infektion während der Kindheit asymptomatisch, obwohl unbehandelte vertikal infizierte Kinder schwere Leberkomplikationen wie Zirrhose und Leberzellkarzinom im Erwachsenenalter entwickeln können. Trotz des Fehlens eines Impfstoffs gegen Hepatitis C und wirksamer Methoden zur Prävention von MTCT nach der Exposition hat die Behandlung mit direkt wirkenden antiviralen Wirkstoffen (DAA) die Aussicht auf eine Eliminierung von HCV auf Bevölkerungsebene erhöht. Hochwirksame, gut verträgliche, orale und kurzzeitige interferonfreie Therapien haben die Behandlung von CHC revolutioniert. Der Zugang zu diesen Therapien könnte jedoch aufgrund der hohen Kosten begrenzt sein. In diesem Überblick stellen wir den aktuellen Stand des Wissens über Epidemiologie, Testung, Überwachung und Behandlung von HCV bei Kindern dar. Wir skizzieren die verbleibenden Therapielücken und Hindernisse bei der Ausrottung der Krankheit.

Key words

hepatitis C - HCV in children - direct-acting antivirals - DAA - Mother-to-child transmission

Schlüsselwörter

Hepatitis C - HCV bei Kindern - direkt wirkende antivirale Wirkstoffe - DAA - Mutter-Kind-Übertragung

Publikationsverlauf

Artikel online veröffentlicht:
18. Dezember 2020

• References

• 1 Abd-Elgawad MM, Baddour NM, Salem MAE. Chronic hepatitis C in children: Clinical spectrum and histopathological study. Alexandria J Med 2013; 49: 363-368.
• 2 Abdel-Hady M, Bunn SK, Sira J. et al. Chronic hepatitis C in children – review of natural history at a National Centre. J Viral Hepat 2011; 18: e535-e540.
• 3 Aniszewska M, Kowalik-Mikołajewska B, Pokorska-Śpiewak M. et al. Anti-HCV testing as a basic standard of monitoring HCV mother-to-child infection: advantages and disadvantages of the method. Przegl Epidemiol 2012; 66: 341-345
• 4 Baker RD, Baker SS. Hepatitis C in children in times of change. Curr Opin Pediatr 2015; 27: 614-618.
• 5 Behairy BES, Sira MM, Zalata KR. et al. Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?. World J Gastroenterol 2016; 22: 4238-4249.
• 6 Beinhardt S, Payer BA, Datz C. et al. A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection. J Hepatol 2013; 59: 4-9.
• 7 Benova L, Mohamoud YA, Calvert C. et al. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis 2014; 59: 765-773.
• 8 Bortolotti F, Verucchi G, Cammà C. et al. Long-Term Course of Chronic Hepatitis C in Children: From Viral Clearance to End-Stage Liver Disease. Gastroenterology 2008; 134: 1900-1907
• 9 Busschots D, Toghanian S, Bielen R. et al. Eliminating viral hepatitis C in Belgium: The micro-elimination approach. BMC Infect. Dis 2020; 20: 1-12
• 10 Le Campion A, Larouche A, Fauteux-Daniel S. et al. Pathogenesis of hepatitis C during pregnancy and childhood. Viruses 2012; 4: 3531-3550
• 11 Cesaro S, Bortolotti F, Petris MG. et al. An Updated Follow-Up of Chronic Hepatitis C After Three Decades of Observation in Pediatric Patients Cured of Malignancy. J Clin Oncol 1996; 14: 1526-1531
• 12 Cho Y, Kim YN, Song B. Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection. Clin Mol Hepatol 2014; 20: 368-375
• 13 Cornberg M, Razavi HA, Alberti A. et al. A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int 2011; 31: 30-60.
• 14 Cottrell E, Chou R, Wasson N. et al. Reducing risk for mother-to-infant transmission of hepatitis C virus: A systemic review for the U.S Preventive Services Task Force. Ann Intern Med 2013; 158: 109-113
• 15 El-Sayed MH, Indolfi G, Hepatitis C. Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination. Semin Liver Dis 2020; 40: 213-224.
• 16 El-Shabrawi MH, Kamal NM. Burden of pediatric hepatitis C. World J Gastroenterol 2013; 19: 7880-7888.
• 17 England K, Thorne C, Harris H. et al. The impact of mode of acquisition on biological markers of paediatric hepatitis C virus infection. J Viral Hepat 2011; 18: 533-541.
• 18 Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008; 48: 148-162
• 19 Farmand S, Wirth S, Löffler H. Spontaneous clearance of hepatitis C virus in vertically infected children. Eur J Pediatr 2012; 171: 253-258.
• 20 Garazzino S, Calitri C, Versace A. et al. Natural history of vertically acquired HCV infection and associated autoimmune phenomena. Eur J Pediatr 2014; 173: 1025-1031.
• 21 Ghamar Chehreh ME, Tabatabaei SV, Khazanehdari S. et al. Effect of cesarean section on the risk of perinatal transmission of hepatitis C virus from HCV-RNA+/HIV- mothers: a meta-analysis. Arch Gynecol Obstet 2011; 283: 255-260.
• 22 Ghany MG, Marks KM, Morgan TR. et al. Hepatitis C Guidance 2019 Update: AASLD‐IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71: 686-721.
• 23 Gower E, Estes C, Blach S. et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61: 45-57.
• 24 Habib M, Mohamed MK, Abdel-Aziz F. et al. Hepatitis C virus infection in a community in the Nile Delta: Risk factors for seropositivity. Hepatology 2001; 33: 248-253.
• 25 Hagan LM, Schinazi RF. Best strategies for global HCV eradication. Liver Int 2013; 33: 68-79
• 26 Indolfi G. Chronic hepatitis C virus infection in children and adolescents: Epidemiology, natural history, and assessment of the safety and efficacy of combination therapy. Adolesc Health Med Ther 2010; 1: 115
• 27 Indolfi G, Azzari C, Resti M. Perinatal transmission of hepatitis C virus. J Pediatr 2013; 163: 1549-1552.
• 28 Indolfi G, Bailey H, Serranti D. et al. Treatment and monitoring of children with chronic hepatitis C in the Pre-DAA era: A European survey of 38 paediatric specialists. J Viral Hepat 2019; 26: 961-968.
• 29 Indolfi G, Easterbrook P, Dusheiko G. et al. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4: 477-487.
• 30 Indolfi G, Thorne C, El Sayed MH. et al. The Challenge of Treating Children With Hepatitis C Virus Infection. J Pediatr Gastroenterol Nutr 2017; 64: 851-854.
• 31 Jonas MM. Children With Hepatitis C. Hepatology 2002; 36: S173-S178.
• 32 Khaderi S, Shepherd R, Goss JA. et al. Hepatitis C in the pediatric population: Transmission, natural history, treatment and liver transplantation. World J Gastroenterol 2014; 20: 11281-11286.
• 33 Lazarus JV, Safreed-Harmon K, Thursz MR. et al. The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations. Semin. Liver Dis. 2018; 38: 181-192.
• 34 Leblebicioglu H, Arends JE, Ozaras R. et al. Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries. Antiviral Res 2018; 150: 9-14.
• 35 Mack CL, Gonzalez-Peralta RP, Gupta N. et al. NASPGHAN Practice Guidelines: Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents. J Pediatr Gastroenterol Nutr 2012; 54: 838-855.
• 36 Mast EE, Hwang L-Y, Seto DSY. et al. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis 2005; 192: 1880-1889.
• 37 Matičič M, Lombardi A, Mondelli MU. et al. Elimination of hepatitis C in Europe: can WHO targets be achieved?. Clin. Microbiol. Infect. 2020; 26: 818-823.
• 38 Murakami J, Nagata I, Iitsuka T. et al. Risk factors for mother-to-child transmission of hepatitis C virus: Maternal high viral load and fetal exposure in the birth canal. Hepatol Res 2012; 42: 648-657.
• 39 Myers S, Khosa G, Kuo IF. et al. Moving towards universal coverage of direct-acting antiviral therapies for hepatitis c infection in Canada: An environmental scan of canadian provinces and international jurisdictions. J Pharm Pharm Sci 2018; 21: 271s-308s
• 40 Negro F. Epidemiology of hepatitis C in Europe. Dig Liver Dis 2014; 46: S158-S164.
• 41 Nguyen J, Barritt A, Jhaveri RR. Cost effectiveness of early treatment with direct-acting antiviral therapy in adolescent patients with hepatitis C infection. J Pediatr 2019; 107: 90-96
• 42 Pawlotsky J-M, Negro F, Aghemo A. et al. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol 2018; 69: 461-511.
• 43 Pawlowska M, Domagalski K, Pniewska A. et al. What’s new in hepatitis C virus infections in children?. World J Gastroenterol 2015; 21: 10783-10789.
• 44 Pembrey L, Newell ML, Tovo PA. et al. The management of HCV infected pregnant women and their children European paediatric HCV network. J Hepatol 2005; 43: 515-525.
• 45 Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M. et al. Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C. BMC Infect Dis 2017; 17: 1-7.
• 46 Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M. et al. Clinical usefulness of new noninvasive serum biomarkers for the assessment of liver fibrosis and steatosis in children with chronic hepatitis C. Clin Exp Hepatol 2017; 3: 198-202.
• 47 Polywka S, Pembrey L, Tovo P-A. et al. Accuracy of HCV-RNA PCR Test. Anticancer Res 2010; 30: 4799-4804.
• 48 Raynes-Greenow C, Polis S, Elliott E. et al. Childhood hepatitis C virus infection: An Australian national surveillance study of incident cases over five years. J Paediatr Child Health 2015; 51: 1115-1120.
• 49 Spearman CW, Dusheiko GM, Hellard M. et al. Hepatitis C. Lancet 2019; 394: 1451-1466
• 50 The European Paediatric Hepatitis C Virus Network. Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 2005; 41: 45-51.
• 51 Tovo P-A, Calitri C, Scolfaro C. et al. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol 2016; 22: 1382-1392
• 52 Vilibic-Cavlek T, Kucinar J, Kaic B. et al. Epidemiology of hepatitis C in Croatia in the European context. World J Gastroenterol 2015; 21: 9476-9493.
• 53 Wen JW, Haber BA. Maternal–Fetal Transmission of Hepatitis C Infection. J Pediatr Gastroenterol Nutr 2014; 58: 278-282.
• 54 Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014; 61: S58-S68.
• 55 Wirth S, Kelly D, Sokal E. et al. Guidance for clinical trials for children and adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2011; 52: 233-237.
• 56 World Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. 2018. Geneva:
• 57 Yeung L. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001; 34: 223-229.