World Journal of Pediatrics

, Volume 9, Issue 3, pp 212–220

Treatment of children with chronic viral hepatitis: what is available and what is in store

  • Pietro Vajro
  • Claudio Veropalumbo
  • Sergio Maddaluno
  • Mariacarolina Salerno
  • Giancarlo Parenti
  • Claudio Pignata
Review Article



At present, therapy of children with chronic hepatitis B and C is still based on few drugs, all burdened by a series of side-effects, unsatisfactory serum conversion rates, and/or drug-resistance. Moreover, selection of subjects to treat with conventional therapies is not univocal, especially during the pediatric age when the disease course is often mild with significant spontaneous seroconversion rate. Our review deals with pros and cons points when a physician decides to design a drug therapy for a child with chronic viral hepatitis, and different possible therapeutic opportunities.


A literature search was performed through PubMed. The newest articles, reviews, systematic reviews, and guidelines were included in this review.


The management of children with viral hepatitis is still controversial over whom and when to treat and the use of drug(s). Novel therapeutic strategies have been evaluated only in clinical and preclinical trials involving, for instance, “therapeutic” vaccines. The data on safety and effectiveness of new drugs are also reviewed.


The results of reported studies confirmed that at least some of the new drugs, with greater efficacy and/or minor side-effects, will be used clinically.

Key words

children hepatitis B hepatitis C therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Giacchino R, Cappelli B. Treatment of viral hepatitis B in children. Expert Opin Pharmacother 2010;11:889–903.PubMedCrossRefGoogle Scholar
  2. 2.
    Vajro P, Paolella G, Nobili V. Children unresponsive to hepatitis B virus vaccination also need celiac disease testing. J Pediatr Gastroenterol Nutr 2012;55:e131.PubMedCrossRefGoogle Scholar
  3. 3.
    Jonas MM, Block JM, Haber BA, Karpen SJ, London WT, Murray KF, et al. Treatment of children with chronic Hepatits B Virus Infection in United States: patient selection and therapeutic options. Hepatology 2010;52:2192–2205.PubMedCrossRefGoogle Scholar
  4. 4.
    Alberti A, Caporaso N. HBV therapy: guidelines and open issues. Dig Liver Dis 2011;43 Suppl 1:S57–63.CrossRefGoogle Scholar
  5. 5.
    Carosi G, Rizzetto M, Alberti A, Cariti G, Colombo M, Craxì A, et al. Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian workshop. Dig Liver Dis 2011;43:259–265.PubMedCrossRefGoogle Scholar
  6. 6.
    European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012;57:167–185.Google Scholar
  7. 7.
    Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:227–242.CrossRefGoogle Scholar
  8. 8.
    Paganelli M, Stephenne X, Sokal EM. Chronic hepatitis B in children and adolescents. J Hepatol 2012;57:885–896.PubMedCrossRefGoogle Scholar
  9. 9.
    Iorio R, Giannattasio A, Cirillo F, D’ Alessandro L, Vegnente A. Long-term outcome in children with chronic hepatitis B: a 24-year observation period. Clin Infect Dis 2007;45:943–949.PubMedCrossRefGoogle Scholar
  10. 10.
    Shah U, Kelly D, Chang MH, Fujisawa T, Heller S, González-Peralta RP, et al. Management of chronic hepatitis B in children. J Pediatr Gastroenterol Nutr 2009;48:399–404.PubMedCrossRefGoogle Scholar
  11. 11.
    Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, et al. Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology 2012;56:2018–2026.PubMedCrossRefGoogle Scholar
  12. 12.
    Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther 2011;34:1145–1158.PubMedCrossRefGoogle Scholar
  13. 13.
    Vajro P, Tedesco M, Fontanella A, De Vincenzo A, Vecchione R, Ammendola R, et al. Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection. Pediatr Infect Dis J 1996;15:223–231.PubMedCrossRefGoogle Scholar
  14. 14.
    Sokal EM, Conjeevaram HS, Roberts EA, Alvarez F, Bern EM, Goyens P, et al. Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial. Gastroenterology 1998;114:988–995.PubMedCrossRefGoogle Scholar
  15. 15.
    Bortolotti F, Jara P, Barbera C, Gregorio GV, Vegnente A, Zancan L, et al. Long term effect of alpha interferon in children with chronic hepatitis B. Gut 2000;46:715–718.PubMedCrossRefGoogle Scholar
  16. 16.
    Gregorio GV, Jara P, Hierro L, Diaz C, de la Vega A, Vegnente A, et al. Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. Hepatology 1996;23:700–707.PubMedCrossRefGoogle Scholar
  17. 17.
    Di Marco V, Giacchino R, Timitilli A, Bortolotti F, Crivellaro C, Calzia R, et al. Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study. J Viral Hepat 1996;3:123–128.PubMedCrossRefGoogle Scholar
  18. 18.
    Sokal EM, Kelly DA, Mizerski J, Badia IB, Areias JA, Schwarz KB, et al. Long-term lamivudine therapy for children with HBeAg-positive chronic hepatitis B. Hepatology 2006;43:225–232.PubMedCrossRefGoogle Scholar
  19. 19.
    Jonas MM, Kelly D, Pollack H, Mizerski J, Sorbel J, Frederick D, et al. Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B. Hepatology 2008;47:1863–1871.PubMedCrossRefGoogle Scholar
  20. 20.
    Akman SA, Kose S, Halicioglu O. Lamivudine and adefovir resistance in children and young adults with chronic hepatitis B. Int J Infect Dis 2010;14:e236–239.PubMedCrossRefGoogle Scholar
  21. 21.
    PawŁowska M, Halota W, Smukalska E, Woźniakowska-Gęsicka T, Kupś J. HBV DNA suppression during entecavir treatment in previously treated children with chronic hepatitis B. Eur J Clin Microbiol Infect Dis 2012;31:571–574.PubMedCrossRefGoogle Scholar
  22. 22.
    Chu M, Cho SM, Choe BH, Cho MH, Kwon S, Lee WK. Virologic responses to add-on adefovir dipivoxil treatment versus entecavir monotherapy in children with lamivudine-resistant chronic hepatitis B. J Pediatr Gastroenterol Nutr 2012;55:648–652.PubMedCrossRefGoogle Scholar
  23. 23.
    van Bömmel F, Trojan J, Deterding K, Wedemeyer H, Wasmuth HE, Hüppe D, et al. Evolution of adefovir-resistant HBV polymerase gene variants after switching to tenofovir disoproxil fumarate monotherapy. Antivir Ther 2012;17:1049–1058.PubMedCrossRefGoogle Scholar
  24. 24.
    Si-Ahmed SN, Pradat P, Zoutendijk R, Buti M, Mallet V, Cruiziat C, et al. Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: a European multicenter study. Antiviral Res 2011;92:90–95.PubMedCrossRefGoogle Scholar
  25. 25.
    Grigsby IF, Pham L, Mansky LM, Gopalakrishnan R, Mansky KC. Tenofovir-associated bone density loss. Ther Clin Risk Manag 2010;6:41–47.PubMedGoogle Scholar
  26. 26.
    Viganò A, Zuccotti GV, Puzzovio M, Pivetti V, Zamproni I, Cerini C, et al. Tenofovir disoproxil fumarate and bone mineral density: a 60-month longitudinal study in a cohort of HIV-infected youths. Antivir Ther 2010;15:1053–1058.PubMedCrossRefGoogle Scholar
  27. 27.
    Han Z, Shi Y, Zhu J, Chen Y, Yin F, Xia L, et al. Forty-eightweek retrospective study of telbivudine and lamivudine treatment in patients withhepatitis B-related cirrhosis. J Viral Hepat 2013;20 Suppl 1:58–64.CrossRefGoogle Scholar
  28. 28.
    Kumar A. Hepatitis B virus infection and pregnancy: a practical approach. Indian J Gastroenterol 2012;31:43–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Pan CQ, Mi LJ, Bunchorntavakul C, Karsdon J, Huang WM, Singhvi G, et al. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case series. Dig Dis Sci 2012;57:2423–2429.PubMedCrossRefGoogle Scholar
  30. 30.
    Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, et al. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009;190:489–492.PubMedGoogle Scholar
  31. 31.
    Keeffe EB, Dieterich DT, Han SB, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B in the United States: 2008 update. Clin Gastroenterol Hepatol 2008;6:1315–1341.PubMedCrossRefGoogle Scholar
  32. 32.
    Shi Z, Yang Y, Ma L, Li X, Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol 2010;116:147–159.PubMedCrossRefGoogle Scholar
  33. 33.
    Pan CQ, Han GR, Jiang HX, Zhao W, Cao MK, Wang CM, et al. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin Gastroenterol Hepatol 2012;10:520–526.PubMedCrossRefGoogle Scholar
  34. 34.
    Cavenaugh JS, Awi D, Mendy M, Hill AV, Whittle H, McConkey SJ. Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection. PLoS One 2011;6:e14626.PubMedCrossRefGoogle Scholar
  35. 35.
    Michel ML, Deng Q, Mancini-Bourgine M. Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges. J Hepatol 2011;54:1286–1296.PubMedCrossRefGoogle Scholar
  36. 36.
    Bortolotti F, Verucchi G, Cammà C, Cabibbo G, Zancan L, Indolfi G, et al. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 2008;134:1900–1907.PubMedCrossRefGoogle Scholar
  37. 37.
    Resti M, Bortolotti F, Vajro P, Maggiore G; Committee of Hepatology of the Italian Society of Pediatric Gastroenterology and Hepatology. Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers. Dig Liver Dis 2003;35:453–457.PubMedCrossRefGoogle Scholar
  38. 38.
    Mohan N, González-Peralta RP, Fujisawa T, Chang MH, Heller S, Jara P, et al. Chronic hepatitis C virus infection in children. J Pediatr Gastroenterol Nutr 2010;50:123–131.PubMedCrossRefGoogle Scholar
  39. 39.
    Shaker OG, Nassar YH, Nour ZA, El-Razki M. Single Nucleotide Polymorphisms of IL-10 and IL-28B as predictors to the response of interferon therapy in HCV genotype 4 infected children. J Pediatr Gastroenterol Nutr 2013 Mar 6. [Epub ahead of print]Google Scholar
  40. 40.
    Murakami J, Nagata I, Iitsuka T, Okamoto M, Kaji S, Hoshika 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.PubMedCrossRefGoogle Scholar
  41. 41.
    Indolfi G, Sambrotta M, Moriondo M, Azzari C, Resti M. Genetic variation in interleukin-28B locus is associated with spontaneous clearance of HCV in children with non-1 viral genotype infection. Hepatology 2011;54:1490–1491.PubMedCrossRefGoogle Scholar
  42. 42.
    Ward JW, Lok AS, Thomas DL, El-Serag HB, Kim WR. Report on a single topic conference on “chronic viral hepatitis-strategies to improve effectiveness of screening and treatment”. Hepatology 2012;55:307–315.PubMedCrossRefGoogle Scholar
  43. 43.
    Wirth S, Kelly D, Sokal E, Socha P, Mieli-Vergani G, Dhawan A, et al. Guidance for clinical trials for children and adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2011;52:233–237.PubMedCrossRefGoogle Scholar
  44. 44.
    Munir S, Saleem S, Idrees M, Tariq A, Butt S, Rauff B, et al. Hepatitis C treatment: current and future perspectives. Virol J 2010;7:296.PubMedCrossRefGoogle Scholar
  45. 45.
    Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz MR, Roberts EA, 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.PubMedCrossRefGoogle Scholar
  46. 46.
    Serranti D, Buonsenso D, Ceccarelli M, Gargiullo L, Ranno O, Valentini P. Pediatric hepatitis C infection: to treat or not to treat…what’s the best for the child? Eur Rev Med Pharmacol Sci 2011;15:1057–1067.PubMedGoogle Scholar
  47. 47.
    Sokal EM, Bourgois A, Stéphenne X, Silveira T, Porta G, Gardovska D, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in children and adolescents. J Hepatol 2010;52:827–831.PubMedCrossRefGoogle Scholar
  48. 48.
    Tsubota A, Fujise K, Namiki Y, Tada N. Peginterferon and ribavirin treatment for hepatitis C virus infection. World J Gastroenterol 2011;17:419–432.PubMedCrossRefGoogle Scholar
  49. 49.
    Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB; American Association for Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011;54:1433–1444.PubMedCrossRefGoogle Scholar
  50. 50.
    Hu J, Doucette K, Hartling L, Tjosvold L, Robinson J. Treatment of hepatitis C in children: a systematic review. PLoS One 2010;5:e11542.PubMedCrossRefGoogle Scholar
  51. 51.
    Nelson DR, Rustgi V, Balan V, Sulkowski MS, Davis GL, Muir AJ, et al. Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C. Clin Gastroenterol Hepatol 2009;7:212–218.PubMedCrossRefGoogle Scholar
  52. 52.
    Long WA, Takov D, Tchernev K, Kotzev I, Rigney A, Krastev Z, et al. Q2 week controlled-release-interferon-alpha2B +ribavirin reduces flu-like symptoms >50% and provides equivalent efficacy in comparison to weekly pegylated-interferonalpha2B + ribavirin in treatment-naive-Genotype-1-chronichepatitis-C: results from empower, a randomized-open-label-12-weekcomparison in 133 patients. J Hepatol 2010;52:S467.CrossRefGoogle Scholar
  53. 53.
    Lawitz E, Younossi Z, Mehra R, Rigney A, Krastev Z, Tchernev K, et al. 444 SVR for controlled-release interferon alpha-2B (CR2B) +ribavirin compared to pegylated interferon alpha-2B (PEG2B) +ribavirin in treatment-naive Genotype-1 (G1) Hepatitis C: final results from select-2. J Hepatol 2011;54:S180–S181.CrossRefGoogle Scholar
  54. 54.
    Lee LY, Tong CY, Wong T, Wilkinson M. New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials. Int J Clin Pract 2012;66:342–355.PubMedCrossRefGoogle Scholar
  55. 55.
    Kwong AD, Kauffman RS, Hurter P, Mueller P. Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. Nat Biotechnol 2011;29:993–1003.PubMedCrossRefGoogle Scholar
  56. 56.
    Torresi J, Johnson D, Wedemeyer H. Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. J Hepatol 2011;54:1273–1285.PubMedCrossRefGoogle Scholar
  57. 57.
    Lapierre P, Troesc M, Alvarez F, Soudeyns H. Structural basis for broad neutralization of hepatitis C virus quasispecies. PloS One 2011;6:e26981.PubMedCrossRefGoogle Scholar
  58. 58.
    Sokal E, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, et al. Management of chronic hepatitis B in childhood. ESPGHAN clinical practice guidelines. J Hepatol 2013 May 23. [Equb ahead of print]Google Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Pietro Vajro
    • 1
    • 3
  • Claudio Veropalumbo
    • 2
  • Sergio Maddaluno
    • 2
  • Mariacarolina Salerno
    • 2
  • Giancarlo Parenti
    • 2
  • Claudio Pignata
    • 2
  1. 1.Department of Medicine and SurgeryUniversity of SalernoBaronissi (Salerno)Italy
  2. 2.Department of Translational Medical Sciences, PediatricsUniversity of Naples “Federico II”NaplesItaly
  3. 3.Department of Medicine and SurgeryUniversity of SalernoBaronissi (Salerno)Italy

Personalised recommendations