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Current Hepatology Reports

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01-06-2017 | Hepatitis B (J Lim, Section Editor)

Management of Chronic Hepatitis B in Children

Authors: Danielle Wendel, Karen F. Murray

Published in: Current Hepatology Reports | Issue 2/2017

Abstract

Purpose of Review

Management of chronic hepatitis B infection poses significant challenges for pediatric providers. Determination of who and when to treat can be difficult as long-term complications such as cirrhosis or hepatocellular carcinoma should be prevented while minimizing the risk of antiviral resistance.

Recent Findings

Many pediatric patients with chronic HBV will achieve natural loss of the HBeAg. Current regimens may be helpful in the setting of active hepatitis with a goal of viral suppression. Even in the rare case of HBsAg loss, viral DNA remains within hepatocytes where it can reactivate. Future treatment regimens being investigated target multiple aspects of the HBV life cycle to improve treatment efficacy.

Summary

Current management strategies involve close monitoring of patients with selective treatment only, so as to limit resistant strains. Future treatments with a variety of therapeutic targets will likely improve and potentially provide a virological cure for chronic HBV infection.

Paganelli M, Stephenne X, Sokal EM. Chronic hepatitis B in children and adolescents. J Hepatol. 2012;57(4):885–96. doi:10.1016/j.jhep.2012.03.036.CrossRefPubMed

Mortality GBD. Causes of death C. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117–71. doi:10.1016/S0140-6736(14)61682-2.CrossRef

WHO. Guidelines for the prevention, care, and treatment of persons with chronic hepatitis B infection. World Health Organization. Geneva; 2015.

• Sokal EM, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, et al. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Hepatol. 2013;59(4):814–29. doi:10.1016/j.jhep.2013.05.016. Guidelines proposed by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) for management of chronic hepatitis B in children CrossRefPubMed

Jonas MM, Block JM, Haber BA, Karpen SJ, London WT, Murray KF, et al. Treatment of children with chronic hepatitis B virus infection in the United States: patient selection and therapeutic options. Hepatology. 2010;52(6):2192–205. doi:10.1002/hep.23934.CrossRefPubMed

National Clinical Guideline Centre. Hepatitis B (Chronic): diagnosis and management of chronic hepatitis B in children, young people, and adults. 2013. https://www.nice.org.uk/guidance/CG165. Accessed 20 Apr 2017.

Clemente MG, Vajro P. An update on the strategies used for the treatment of chronic hepatitis B in children. Expert Rev Gastroenterol Hepatol. 2016;10(5):649–58. doi:10.1586/17474124.2016.1139450.CrossRefPubMed

Wu JF, Chang MH. Natural history of chronic hepatitis B virus infection from infancy to adult life - the mechanism of inflammation triggering and long-term impacts. J Biomed Sci. 2015;22:92. doi:10.1186/s12929-015-0199-y.CrossRefPubMedPubMedCentral

Bortolotti F, Guido M, Bartolacci S, Cadrobbi P, Crivellaro C, Noventa F, et al. Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study. Hepatology. 2006;43(3):556–62. doi:10.1002/hep.21077.CrossRefPubMed

10.

Haber BA, Block JM, Jonas MM, Karpen SJ, London WT, McMahon BJ, et al. Recommendations for screening, monitoring, and referral of pediatric chronic hepatitis B. Pediatrics. 2009;124(5):e1007–13. doi:10.1542/peds.2009-0567.CrossRefPubMed

11.

McMahon BJ, Alward WL, Hall DB, Heyward WL, Bender TR, Francis DP, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis. 1985;151(4):599–603.CrossRefPubMed

12.

Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A. Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A. 1990;87(17):6599–603.CrossRefPubMedPubMedCentral

13.

Schwarz KB, Cloonan YK, Ling SC, Murray KF, Rodriguez-Baez N, Schwarzenberg SJ, et al. Children with chronic hepatitis B in the United States and Canada. J Pediatr. 2015;167(6):1287–1294 e2. doi:10.1016/j.jpeds.2015.08.021.CrossRefPubMedPubMedCentral

14.

Livingston SE, Simonetti JP, Bulkow LR, Homan CE, Snowball MM, Cagle HH, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes a, B, C, D, and F. Gastroenterology. 2007;133(5):1452–7. doi:10.1053/j.gastro.2007.08.010.CrossRefPubMed

15.

Wen WH, Chang MH, Hsu HY, Ni YH, Chen HL. The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection. J Pediatr. 2004;144(3):397–9. doi:10.1016/j.jpeds.2003.11.022.CrossRefPubMed

16.

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. doi:10.1001/jama.295.1.65.CrossRefPubMed

17.

Ni YH, Chang MH, Wang KJ, Hsu HY, Chen HL, Kao JH, et al. Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology. 2004;127(6):1733–8.CrossRefPubMed

18.

Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol. 2011;26(Suppl 1):123–30. doi:10.1111/j.1440-1746.2010.06541.x.CrossRefPubMed

19.

Iorio R, Giannattasio A, Cirillo F. L DA, Vegnente a. Long-term outcome in children with chronic hepatitis B: a 24-year observation period. Clin Infect Dis. 2007;45(8):943–9. doi:10.1086/521864.CrossRefPubMed

20.

Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35(6):1522–7. doi:10.1053/jhep.2002.33638.CrossRefPubMed

21.

• Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. doi:10.1002/hep.28156. These are the most recently published guidelines which were proposed by the American Association for the Study of Liver Disease for Management of chroinic hepatitis B in adults and children CrossRefPubMed

22.

Hai H, Tamori A, Kawada N. Role of hepatitis B virus DNA integration in human hepatocarcinogenesis. World J Gastroenterol. 2014;20(20):6236–43. doi:10.3748/wjg.v20.i20.6236.CrossRefPubMedPubMedCentral

23.

Mason WS, Gill US, Litwin S, Zhou Y, Peri S, Pop O, et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant. Gastroenterology. 2016; doi:10.1053/j.gastro.2016.07.012.PubMed

24.

Rizzetto M. Hepatitis D: thirty years after. J Hepatol. 2009;50(5):1043–50. doi:10.1016/j.jhep.2009.01.004.CrossRefPubMed

25.

Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R, et al. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009;136(5):1629–38. doi:10.1053/j.gastro.2009.01.052.CrossRefPubMed

26.

Xue MM, Glenn JS, Leung DH. Hepatitis D in children. J Pediatr Gastroenterol Nutr. 2015;61(3):271–81. doi:10.1097/MPG.0000000000000859.CrossRefPubMed

27.

Ngui SL, Andrews NJ, Underhill GS, Heptonstall J, Teo CG. Failed postnatal immunoprophylaxis for hepatitis B: characteristics of maternal hepatitis B virus as risk factors. Clin Infect Dis. 1998;27(1):100–6.CrossRefPubMed

28.

Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374(24):2324–34. doi:10.1056/NEJMoa1508660.CrossRefPubMed

29.

Hung HF, Chen TH. Probabilistic cost-effectiveness analysis of the long-term effect of universal hepatitis B vaccination: an experience from Taiwan with high hepatitis B virus infection and hepatitis B e antigen positive prevalence. Vaccine. 2009;27(48):6770–6. doi:10.1016/j.vaccine.2009.08.082.CrossRefPubMed

30.

Siddiqui MR, Gay N, Edmunds WJ, Ramsay M. Economic evaluation of infant and adolescent hepatitis B vaccination in the UK. Vaccine. 2011;29(3):466–75. doi:10.1016/j.vaccine.2010.10.075.CrossRefPubMed

31.

Beasley RP. Development of hepatitis B vaccine. JAMA. 2009;302(3):322–4. doi:10.1001/jama.2009.1024.CrossRefPubMed

32.

Chen HL, Lin LH, Hu FC, Lee JT, Lin WT, Yang YJ, et al. Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV. Gastroenterology. 2012;142(4):773–781 e2. doi:10.1053/j.gastro.2011.12.035.CrossRefPubMed

33.

Publication WHO. Hepatitis B vaccines: WHO position paper--recommendations. Vaccine. 2010;28(3):589–90. doi:10.1016/j.vaccine.2009.10.110.CrossRef

34.

Jafarzadeh A, Zarei S, Shokri F. Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates. Vaccine. 2008;26(2):269–76. doi:10.1016/j.vaccine.2007.10.044.CrossRefPubMed

35.

Vajro P, Paolella G, Nobili V. Children unresponsive to hepatitis B virus vaccination also need celiac disease testing. J Pediatr Gastroenterol Nutr. 2012;55(4):e131. doi:10.1097/MPG.0b013e31825d4ac9.CrossRefPubMed

36.

Whitaker JA, Rouphael NG, Edupuganti S, Lai L, Mulligan MJ. Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. Lancet Infect Dis. 2012;12(12):966–76. doi:10.1016/S1473-3099(12)70243-8.CrossRefPubMedPubMedCentral

37.

Yang J, Zeng XM, Men YL, Zhao LS. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus--a systematic review. Virol J. 2008;5:100. doi:10.1186/1743-422X-5-100.CrossRefPubMedPubMedCentral

38.

WHO. Hepatitis B and breastfeeding. J Int Assoc Physicians AIDS Care. 1998;4(7):20–1.

39.

Chen X, Chen J, Wen J, Xu C, Zhang S, Zhou YH, et al. Breastfeeding is not a risk factor for mother-to-child transmission of hepatitis B virus. PLoS One. 2013;8(1):e55303. doi:10.1371/journal.pone.0055303.CrossRefPubMedPubMedCentral

40.

Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, Kerkar N, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology. 2010;138(4):1357–1364, 64 e1-2. doi:10.1053/j.gastro.2009.12.052.CrossRefPubMedPubMedCentral

41.

Zoulim F. Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology. 2009;137(5):1593–1608 e1-2. doi:10.1053/j.gastro.2009.08.063.CrossRefPubMed

42.

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(5):988–95.CrossRefPubMed

43.

Hom X, Little NR, Gardner SD, Jonas MM. Predictors of virologic response to lamivudine treatment in children with chronic hepatitis B infection. Pediatr Infect Dis J. 2004;23(5):441–5.CrossRefPubMed

44.

Wang YJ, Yang L, Zuo JP. Recent developments in antivirals against hepatitis B virus. Virus Res. 2016;213:205–13. doi:10.1016/j.virusres.2015.12.014.CrossRefPubMed

45.

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(5):715–8.CrossRefPubMedPubMedCentral

46.

Vo Thi Diem H, Bourgois A, Bontems P, Goyens P, Buts JP, Nackers F, et al. Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls. J Pediatr Gastroenterol Nutr. 2005;40(2):141–5.CrossRefPubMed

47.

European Association For The Study Of The L. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167–85. doi:10.1016/j.jhep.2012.02.010.CrossRef

48.

Kobak GE, MacKenzie T, Sokol RJ, Narkewicz MR. Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger. J Pediatr. 2004;145(3):340–5. doi:10.1016/j.jpeds.2004.05.046.CrossRefPubMed

49.

Jonas MM, Mizerski J, Badia IB, Areias JA, Schwarz KB, Little NR, et al. Clinical trial of lamivudine in children with chronic hepatitis B. N Engl J Med. 2002;346(22):1706–13. doi:10.1056/NEJMoa012452.CrossRefPubMed

50.

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(2):225–32. doi:10.1002/hep.21020.CrossRefPubMed

51.

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(6):1863–71. doi:10.1002/hep.22250.CrossRefPubMed

52.

• Jonas MM, Chang MH, Sokal E, Schwarz KB, Kelly D, Kim KM, et al. Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B. Hepatology. 2016;63(2):377–87. doi:10.1002/hep.28015. This is the most recent study which supported the use of entecavir in children age 2 to 18 years CrossRefPubMed

53.

• 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(6):2018–26. doi:10.1002/hep.25818. Tenofovir was shown to be an effective treatment for adolescents age 12 to 18 years with chronic hepatitis B with no evidance of resistance in this important trial CrossRefPubMed

54.

Stein DS, Ke J, Uy G, Bosheva M, Qi Y, Praestgaard J, et al. Phase I, open-label, single-dose study to evaluate the pharmacokinetics and safety of telbivudine in children and adolescents with chronic hepatitis B. Antimicrob Agents Chemother. 2013;57(9):4128–33. doi:10.1128/AAC.00117-13.CrossRefPubMedPubMedCentral

55.

Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52(3):886–93. doi:10.1002/hep.23785.CrossRefPubMed

56.

Gordon SC, Krastev Z, Horban A, Petersen J, Sperl J, Dinh P, et al. Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load. Hepatology. 2013;58(2):505–13. doi:10.1002/hep.26277.CrossRefPubMedPubMedCentral

57.

Thio CL, Seaberg EC, Skolasky Jr R, Phair J, Visscher B, Munoz A, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the multicenter cohort study (MACS). Lancet. 2002;360(9349):1921–6.CrossRefPubMed

58.

Benhamou Y, Bochet M, Thibault V, Di Martino V, Caumes E, Bricaire F, et al. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology. 1999;30(5):1302–6. doi:10.1002/hep.510300525.CrossRefPubMed

59.

Soriano V, Puoti M, Bonacini M, Brook G, Cargnel A, Rockstroh J, et al. Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV international panel. AIDS. 2005;19(3):221–40.PubMed

60.

Dalekos GN, Galanakis E, Zervou E, Tzoufi M, Lapatsanis PD, Tsianos EV. Interferon-alpha treatment of children with chronic hepatitis D virus infection: the Greek experience. Hepato-Gastroenterology. 2000;47(34):1072–6.PubMed

61.

Aziz S, Rajper J, Noor-ul-Ain W, Mehnaz A, Masroor M, Chang MH. Interferon-alpha treatment of children and young adults with chronic hepatitis delta virus (HDV) infection. J Coll Physicians Surg Pak. 2011;21(12):735–40.

62.

Boucle S, Bassit L, Ehteshami M, Schinazi RF. Toward elimination of hepatitis B virus using novel drugs, approaches, and combined modalities. Clin Liver Dis. 2016;20(4):737–49. doi:10.1016/j.cld.2016.07.001.CrossRefPubMed

63.

Ebert G, Allison C, Preston S, Cooney J, Toe JG, Stutz MD, et al. Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci U S A. 2015;112(18):5803–8. doi:10.1073/pnas.1502400112.CrossRefPubMedPubMedCentral

64.

• Petersen J, Thompson AJ, Levrero M. Aiming for cure in HBV and HDV infection. J Hepatol. 2016;65(4):835–48. doi:10.1016/j.jhep.2016.05.043. This recent review is an excellent summary of current trials and potential future targets for treatment of chronic hepatitis B CrossRefPubMed

65.

Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016;65(3):483–9. doi:10.1016/j.jhep.2016.04.013.CrossRefPubMed

Title: Management of Chronic Hepatitis B in Children
Authors: Danielle Wendel
Karen F. Murray
Publication date: 01-06-2017
Publisher: Springer US
Published in: Current Hepatology Reports / Issue 2/2017
Electronic ISSN: 2195-9595
DOI: https://doi.org/10.1007/s11901-017-0338-x

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