Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지

소아 만성 B형 간염의 관리와 치료

The management and treatment of chronic hepatitis B in Korean children

  • 최병호 (경북대학교 의과대학 소아과학교실)
  • Choe, Byung-Ho (Department of Pediatrics, Kyungpook National University School of Medicine)
  • 투고 : 2007.07.25
  • 심사 : 2007.08.30
  • 발행 : 2007.09.15
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초록

Interferon (IFN) alpha has been the first line therapy of chronic hepatitis B in children, but HBeAg seroconversion occurred in 26% of treated children compared to 11% of controls in multinational randomized controlled study. Recently, lamivudine was shown to be a potent inhibitor of Hepatitis B virus (HBV) reproduction both in HBeAg positive and in HBeAg negative (the pre-core mutant form) chronic hepatitis in randomized studies worldwide. Lamivudine therapy led to considerable improvement in the seroconversion rate of HBeAg in children with chronic hepatitis B, though long-term therapy resulted in the expansion of lamivudine-resistant mutant viruses. Combination therapy with lamivudine plus alpha-IFN does not seem to improve HBe Ag seroconversion. Above all, the most effective way to prevent hepatitis B is universal HBV vaccination.

키워드

참고문헌

  1. Choe BH. Hepatitis B Vaccine: Prevention of Perinatal Infection and Management of Nonresponder. Korean J Pediatr Gastroenterol Nutr 2007;10:91-100
  2. Choe BH. Management of chronic hepatitis B in children. In: Joint seminar of Korean gastroenterology society; 2003; Seoul; 2003. p. 250-61
  3. Bortolotti F, Cadrobbi P, Crivellaro C, Guido M, Rugge M, Noventa F, et al. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterology 1990;99:805-10 https://doi.org/10.1016/0016-5085(90)90972-4
  4. Choe BH, Lee JH, Jang YC, Jang CH, Oh KW, Kwon S, et al. Long-term therapeutic efficacy of lamivudine compared to interferon-alpha in children with chronic hepatitis B: the younger the better. J Pediatr Gastroenterol Nutr 2007; 44:92-8 https://doi.org/10.1097/01.mpg.0000243439.47334.4e
  5. Kim JO, Choe BH. Long-term lamivudine treatment in children and adolescence with chronic hepatitis B: predictors of therapeutic response and lamivudine resistance. In: Seoul International Liver Symposium; 2007; Seoul; 2007. p. in press
  6. Torre D, Tambini R. Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis. Clin Infect Dis 1996;23:131-7 https://doi.org/10.1093/clinids/23.1.131
  7. Jonas MM, Kelley DA, Mizerski J, Badia IB, Areias JA, Schwarz KB, et al. Clinical trial of lamivudine in children with chronic hepatitis B. N Engl J Med 2002;346:1706-13 https://doi.org/10.1056/NEJMoa012452
  8. Hepatitis B. In: LK Pickering, ed. Red Book: 2006 Report of the Committee on Infectious Diseases 27th ed. Elk Grove Village, IL: Committee on Infectious Diseases, American Academy of Pediatrics 2006;335-55
  9. Shapiro CN. Epidemology of hepatitis B. Pediatr Infect Dis J 1993;12:433-7 https://doi.org/10.1097/00006454-199305000-00036
  10. Ohto H, Lin HH, Kawana T, Etoh T, Tohyama H. Intrauterine transmission of hepatitis B virus is closely related to placental leakage. J Med Virol 1987;21:1-6 https://doi.org/10.1002/jmv.1890210102
  11. Stiehm ER, Ammann AJ, Cherry JD. Elevated cord macroglobulins in the diagnosis of intrauterine infections. N Engl J Med 1966;275:971-7 https://doi.org/10.1056/NEJM196611032751801
  12. Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol 2002;67:20-6 https://doi.org/10.1002/jmv.2187
  13. Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol 2002;99:1049-52 https://doi.org/10.1016/S0029-7844(02)02000-8
  14. Wang JS, Zhu QR, Wang XH. Breastfeeding does not pose any additional risk of immunoprophylaxis failure on infants of HBV carrier mothers. Int J Clin Pract 2003;57:100-2
  15. Hepatits B. In: Guideline of vaccination 5th ed: Korean J Pediatrics 2002:48-60
  16. Kim B, Seo K, Park S, Kim Y, Park O, Lee H, et al. Evaluation of prevention program for neonatal vertical transmission from HBsAg positive mother in Korea. Korean J Obstet Gynecol 2005;48:2067-72
  17. Hsu HY, Chang MH, Chen DS, Lee CY, Sung JL. Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan. J Med Virol 1986;18:301-7 https://doi.org/10.1002/jmv.1890180402
  18. Ni YH, Chang MH, Huang LM, Chen HL, Hsu HY, Chiu TY, et al. Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 2001;135:796-800 https://doi.org/10.7326/0003-4819-135-9-200111060-00009
  19. Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 1997;336:1855-9 https://doi.org/10.1056/NEJM199706263362602
  20. Hsu HY, Chang MH, Liaw SH, Ni YH, Chen HL. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology 1999;30:1312-7 https://doi.org/10.1002/hep.510300511
  21. Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK. Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Lancet 2002;359:1488-9 https://doi.org/10.1016/S0140-6736(02)08425-8
  22. van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat 2003;10:294-7 https://doi.org/10.1046/j.1365-2893.2003.00440.x
  23. Lee SD, Lo KJ, Tsai YT, Wu JC, Wu TC, Yang ZL, et al. Role of caesarean section in prevention of mother-infant transmission of hepatitis B virus. Lancet 1988;2:833-4
  24. Wang J, Zhu Q, Zhang X. Effect of delivery mode on maternal- infant transmission of hepatitis B virus by immunoprophylaxis. Chin Med J 2002;115:1510-2
  25. Jonas MM. Interferon-alpha for viral hepatitis. J Pediatr Gastroenterol Nutr 1996;23:93-106 https://doi.org/10.1097/00005176-199608000-00001
  26. Desmet VJ. Immunopathology of chronic viral hepatitis. Hepatogastroenterology 1991;38:14-21
  27. 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;35:1522-7 https://doi.org/10.1053/jhep.2002.33638
  28. Hsu HY, Chang MH, Lee CY, Chen JS, Hsu HC, Chen DS. Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection. Hepatology 1992;15:382-6 https://doi.org/10.1002/hep.1840150304
  29. Kim Y, Baek SY, Eom JH, Chung KS. Natural History of Chronic Hepatitis B in Children. Korean J Pediatr 2004;47: 282-9.
  30. Godra A, Jonas M, Perez-Atayde A. Histopathology of the liver in children with chronic hepatitis B. Mod Pathol 2005; 18:346A
  31. Hsu HC, Lin YH, Chang MH, Su IJ, Chen DS. Pathology of chronic hepatitis B virus infection in children: with special reference to the intrahepatic expression of hepatitis B virus antigens. Hepatology 1988;8:378-82 https://doi.org/10.1002/hep.1840080232
  32. Bortolotti F, Calzia R, Cadrobbi P, Giacchini R, Ciravegna B, Armigliato M, et al. Liver cirrhosis associated with chronic hepatitis B virus infection in childhood. J Pediatr 1986;108: 224-7. https://doi.org/10.1016/S0022-3476(86)80987-8
  33. Hsu HC, Wu MZ, Chang MH, Su IJ, Chen DS. Childhood hepatocellular carcinoma develops exclusively in hepatitis B surfaceantigen carriers in three decades in Taiwan. Report of 51 cases strongly associated with rapid development of liver cirrhosis. J Hepatol 1987;5:260-7 https://doi.org/10.1016/S0168-8278(87)80030-2
  34. Chu CM, Hung SJ, Lin J, Tai DI, Liaw YF. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med 2004;116:829-34 https://doi.org/10.1016/j.amjmed.2003.12.040
  35. 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;43:556-62 https://doi.org/10.1002/hep.21077
  36. Zacharakis G, Koskinas J, Kotsiou S, Pouliou E, Papoutselis M, Tzara F, et al. Natural history of chronic hepatitis B virus infection in children of different ethnic origins: a cohort study with upto 12 years' follow-up in northern Greece. J Pediatr Gastroenterol Nutr 2007;44:84-91 https://doi.org/10.1097/01.mpg.0000243438.47334.07
  37. Perrillo RP. Treatment of chronic hepatitis B with interferon: experience in western countries. Semin Liver Dis 1989;9: 240-8 https://doi.org/10.1055/s-2008-1040517
  38. Perrillo RP. Treatment of chronic hepatitis B with interferon: experience in western countries. Semin Liver Dis 1989;9: 240-8 https://doi.org/10.1055/s-2008-1040517
  39. Lai CL, Lin HJ, Wu PC. Recombinant alpha 2-interferon treatment in children with chronic hepatitis B. Lancet 1988;1:762
  40. Lai CL, Lok AS, Lin HJ, Wu PC, Yeoh EK, Yeung CY. Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children. Lancet 1987;2:877-80
  41. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med 1997;336:347-56 https://doi.org/10.1056/NEJM199701303360507
  42. Wai CT, Lok AS. Treatment of hepatitis B. J Gastroenterol 2002;37:771-8 https://doi.org/10.1007/s005350200129
  43. Hoofnagle JH. Alpha-interferon therapy of chronic hepatitis B. Current status and recommendations. J Hepatol 1990;11 Suppl 1:S100-7
  44. Broderick A, Jonas MM. Management of hepatitis B in children. Clin Liver Dis 2004;8:387-401 https://doi.org/10.1016/j.cld.2004.02.007
  45. Conjeevaram HS, Di Bisceglie AM. Management of chronic viral hepatitis in children. J Pediatr Gastroenterol Nutr 1995;20:365-75 https://doi.org/10.1097/00005176-199505000-00001
  46. Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422-7 https://doi.org/10.1056/NEJM199605303342202
  47. Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology 1999;29:971-5 https://doi.org/10.1002/hep.510290312
  48. Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC, Jr., Lindsay K, Payne J, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group. N Engl J Med 1990;323:295- 301 https://doi.org/10.1056/NEJM199008023230503
  49. Choe BH, Ko CW. Combined therapy of alfa-interferon and thymodulin on children with chronic active hepatitis B. Korean J Pediatr Gastroenterol Nutr 1998;1:79-89
  50. Jang CH, Lee KH, Hwang WK, Oh KW, Park WS, Lee JH, et al. The comparison of interferon-alpha treatment by dosages and retreatment for chronic hepatitis B in children. Korean J Pediatr Gastroenterol Nutr 2003;6:152-60
  51. 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;46:715-8 https://doi.org/10.1136/gut.46.5.715
  52. 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;40:141-5 https://doi.org/10.1097/00005176-200502000-00011
  53. 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;145:340-5. https://doi.org/10.1016/j.jpeds.2004.05.046
  54. Kim HK, Choi BH, Kim KM, Kang KH, Lim IS, Choi ES. Factors Predictive of Response to Interferon-alpha Therapy in Children with Chronic Hepatitis B. J Korean Pediatr Soc 2000;43:514-9
  55. Kim HS, Kim JW, Chung KS. Treatment of chronic hepatitis B in children with prednisolone withdrawal followed by recombinant interferon alpha. Yonsei Med J 1998;39:309-16 https://doi.org/10.3349/ymj.1998.39.4.309
  56. Ko JS, Chung JY, Seo JK, Jang JJ. Serological and Histological Changes after Interferon Alfa Therapy in Children with Chronic Hepatitis B. Korean J Pediatr Gastroenterol Nutr 2000;3:56-62
  57. 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;114:988-95 https://doi.org/10.1016/S0016-5085(98)70318-X
  58. Yuen MF, Hui CK, Cheng CC, Wu CH, Lai YP, Lai CL. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: The effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications. Hepatology 2001;34:139- 45 https://doi.org/10.1053/jhep.2001.25273
  59. 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;127:1733-8 https://doi.org/10.1053/j.gastro.2004.09.048
  60. Wai CT, Chu CJ, Hussain M, Lok AS. HBV genotype B is associated with better response to interferon therapy in HBeAg (+) chronic hepatitis than genotype C. Hepatology 2002;36:1425-30
  61. Lee SH, Han SH, Cho SC, Roh BJ, Sohn JH, Kim DA, et al. Distribution of HBV Genotypes in Patients With Chronic HBV Infection in Korea. Korean J Hepatol 2001;7:373-80
  62. Sakai T, Shiraki K, Inoue H, Okano H, Deguchi M, Sugimoto K, et al. Efficacy of long-term interferon therapy in chronic hepatitis B patients with HBV genotype C. Int J Mol Med 2002;10:201-4
  63. Giacchino R, Main J, Timitilli A, Giambartolomei G, Facco F, Cirillo C, et al. Dual-centre, double-blind, randomised trial of lymphoblastoid interferon alpha with or withoutsteroid pretreatment in children with chronic hepatitis B. Liver 1995;15:143-8 https://doi.org/10.1111/j.1600-0676.1995.tb00661.x
  64. Gurakan F, Kocak N, Ozen H, Yuce A. Comparison of standard and high dosage recombinant interferon alpha 2b for treatment of children with chronic hepatitis B infection. Pediatr Infect Dis J 2000;19:52-6 https://doi.org/10.1097/00006454-200001000-00011
  65. Flink HJ, van Zonneveld M, Hansen BE, de Man RA, Schalm SW, Janssen HL. Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype. Am J Gastroenterol 2006; 101:297-303 https://doi.org/10.1111/j.1572-0241.2006.00418.x
  66. Fattovich G, Giustina G, Favarato S, Ruol A. A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 1996;24:38-47 https://doi.org/10.1016/S0168-8278(96)80184-X
  67. Kuloglu Z, Kansu A, Berberoglu M, Adiyaman P, Ocal G, Girgin N. The incidence and evolution of thyroid dysfunction during interferon-alpha therapy in children with chronic hepatitis B infection. J Pediatr Endocrinol Metab 2007;20: 237-45
  68. Boni C, Bertoletti A, Penna A, Cavalli A, Pilli M, Urbani S, et al. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998;102:968-75 https://doi.org/10.1172/JCI3731
  69. Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 1999;341:1256-63 https://doi.org/10.1056/NEJM199910213411702
  70. Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med 1995;333:1657-61 https://doi.org/10.1056/NEJM199512213332501
  71. Nevens F, Main J, Honkoop P, Tyrrell DL, Barber J, Sullivan MT, et al. Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study. Gastroenterology 1997;113:1258-63 https://doi.org/10.1053/gast.1997.v113.pm9322520
  72. Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, et al. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med 1998;339:61-8 https://doi.org/10.1056/NEJM199807093390201
  73. Lau DT, Khokhar MF, Doo E, Ghany MG, Herion D, Park Y, et al. Long-term therapy of chronic hepatitis B with lamivudine. Hepatology 2000;32:828-34 https://doi.org/10.1053/jhep.2000.17912
  74. Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000;32:803-6 https://doi.org/10.1053/jhep.2000.16665
  75. Park N, Shin J, Park J, Bang S, Kim D, Joo K. Predictive Factors and Efficacy of Lamivudine Treatment in Chronic Hepatitis B Infection. Korean J Gastroenterol 2003;42:303-12
  76. Schiff ER, Dienstag JL, Karayalcin S, Grimm IS, Perrillo RP, Husa P, et al. Lamivudine and 24 weeks of lamivudine/ interferon combination therapy for hepatitis B e antigenpositive chronic hepatitis B in interferon nonresponders. J Hepatol 2003;38:818-26 https://doi.org/10.1016/S0168-8278(03)00076-X
  77. Serfaty L, Thabut D, Zoulim F, Andreani T, Chazouilleres O, Carbonell N, et al. Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: results of a pilot study. Hepatology 2001;34:573-7
  78. Cha C, Sohn Y, Jang S, Lee H, Lee K, Shin E, et al. Genotype Analysis of Hepatitis B Virus Isolated from Korean Hepatitis Patients. Korean J Lab Med 2003;23:352-6
  79. Chan HL, Wong ML, Hui AY, Chim AM, Tse AM, Hung LC, et al. Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment. World J Gastroenterol 2003;9:2695-7 https://doi.org/10.3748/wjg.v9.i12.2695
  80. Leung NW, Lai CL, Chang TT, Guan R, Lee CM, Ng KY, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 2001;33: 1527-32 https://doi.org/10.1053/jhep.2001.25084
  81. Yao GB, Wang BE, Cui ZY, Yao JL, Zeng MD. [The longterm efficacy of lamivudine in chronic hepatitis B: interim analysis of 3-year's clinical course]. Zhonghua Nei Ke Za Zhi 2003;42:382-7
  82. Consensus statements on the prevention and management of hepatitis B and hepatitis C in the Asia-Pacific region. Core Working Party for Asia-Pacific Consensus on Hepatitis B and C. J Gastroenterol Hepatol 2000;15:825-41 https://doi.org/10.1046/j.1440-1746.2000.02324.x
  83. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2001;34:1225-41 https://doi.org/10.1053/jhep.2001.29401
  84. Liaw YF, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology 2000;119:172-80 https://doi.org/10.1053/gast.2000.8559
  85. Moraleda G, Saputelli J, Aldrich CE, Averett D, Condreay L, Mason WS. Lack of effect of antiviral therapy in nondividing hepatocyte cultures on the closed circular DNA of woodchuck hepatitis virus. J Virol 1997;71:9392-9
  86. Zeuzem S, de Man RA, Honkoop P, Roth WK, Schalm SW, Schmidt JM. Dynamics of hepatitis B virus infection in vivo. J Hepatol 1997;27:431-6 https://doi.org/10.1016/S0168-8278(97)80345-5
  87. Hong S, Han K, Ahn S, Paik Y, Moon B, Chon C, et al. Long-term Efficacy and Durability of Lamivudine Therapy in Patients with Chronic Hepatitis B. Korean J Hepatol 2001;7:423-31
  88. Allen MI, Deslauriers M, Andrews CW, Tipples GA, Walters KA, Tyrrell DL, et al. Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group. Hepatology 1998; 27:1670-7 https://doi.org/10.1002/hep.510270628
  89. Liaw YF, Chien RN, Yeh CT, Tsai SL, Chu CM. Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy. Hepatology 1999;30:567-72 https://doi.org/10.1002/hep.510300221
  90. Melegari M, Scaglioni PP, Wands JR. Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective. Hepatology 1998;27:628-33 https://doi.org/10.1002/hep.510270243
  91. Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003;125:1714-22 https://doi.org/10.1053/j.gastro.2003.09.033
  92. Artan R. Lamivudine monotherapy in children with immunetolerant chronic hepatitis B virus. J Chemother 2005;17: 198-202 https://doi.org/10.1179/joc.2005.17.2.198
  93. Choe BH, Oh KW, Park WS, Lee JH, Kwon S, Ko CW, et al. Comparison of therapeutic efficacy between lamivudine and alpha-interferon in Korean children with chronic hepatitis B. J Pediatr Gastroenterol Nutr 2003;37:379 https://doi.org/10.1097/00005176-200309000-00040
  94. Jang YC, Cho MH, Choe BH. Three years' cumulative therapeutic efficacy and long-term durability of lamivudine in Korean children with chronic hepatitis B. Korean J Pediatr Gastroenterol Nutr 2004;7:197-207
  95. Choe BH, Lee JH, Lee TH, Kim JM. Long-term Therapeutic Efficacy of Lamivudine Compared to Interferon-alpha in Children with Chronic Hepatitis B: A 6-Year Follow-up Study in Korea. J Gastroenterol Hepatol 2005;20:A338
  96. 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: 441-5 https://doi.org/10.1097/01.inf.0000126412.93562.f5
  97. Zuccotti GV, Cucchi C, Gracchi V, D'Auria E, Riva E, Tagger A. A 1-year trial of lamivudine for chronic hepatitis B in children. J Int Med Res 2002;30:200-2 https://doi.org/10.1177/147323000203000214
  98. Dikici B, Ozgenc F, Kalayci AG, Targan S, Ozkan T, Selimoglu A, et al. Current therapeutic approaches in childhood chronic hepatitis B infection: a multicenter study. J Gastroenterol Hepatol 2004;19:127-33 https://doi.org/10.1111/j.1440-1746.2004.03209.x
  99. Figlerowicz M, Kowala-Piaskowska A, Filipowicz M, Bujnowska A, Mozer-Lisewska I, Sluzewski W. Efficacy of lamivudine in the treatment of children with chronic hepatitis B. Hepatol Res 2005;31:217-22 https://doi.org/10.1016/j.hepres.2005.02.003
  100. Marrone A, Zampino R, Portella G, Grimaldi M, Mangoni ED, Santarpia L, et al. Three-phase sequential combined treatment with lamivudine and interferon in young patients with chronic hepatitis B. J Viral Hepat 2005;12:186-91 https://doi.org/10.1111/j.1365-2893.2005.00619.x
  101. Dikici B, Ece A, Bosnak M. Which combination should be preferred in the management of children with chronic hepatitis B infection? J Clin Gastroenterol 2005;39:745-6. https://doi.org/10.1097/01.mcg.0000173934.46654.1e
  102. Ozgenc F, Dikici B, Targan S, Doganci T, Akman S, Aydogdu S, et al. Comparison of antiviral effect of lamivudine with interferon-alpha2a versus -alpha2b in children with chronic hepatitis B infection. Antivir Ther 2004;9:23- 6
  103. 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;43:225-32 https://doi.org/10.1002/hep.21020
  104. Choe BH, Kim JM, Lee JH, Jang YC, Jang CH, Oh KW, et al. Lamivudine Treatment in Children with Chronic Hepatitis B: Long-term Therapeutic Response, Optimal Duration and Resistance. In: the 39th Annual Meeting of ESPGHAN; 2006; Dresden, Germany; 2006. p. 47
  105. Hartman C, Berkowitz D, Eshach-Adiv O, Hino B, Rimon N, Satinger I, et al. Long-term lamivudine therapy for chronic hepatitis B infection in children unresponsive to interferon. J Pediatr Gastroenterol Nutr 2006;43:494-8 https://doi.org/10.1097/01.mpg.0000235982.34323.67
  106. Ozgenc F, Arikan C, Sertoz RY, Nart D, Aydogdu S, Yagci RV. Effect of long-term lamivudine in chronic hepatitis B virus-infected children. Antivir Ther 2004;9:729-32
  107. Hartman C, Berkowitz D, Shouval D, Eshach-Adiv O, Hino B, Rimon N, et al. Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon. Pediatr Infect Dis J 2003;22:224-9 https://doi.org/10.1097/00006454-200303000-00004
  108. Selimoglu MA, Aydogdu S, Unal F, Zeytinoglu A, Yuce G, Yagci RV. Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children. Pediatr Int 2002;44:404-8 https://doi.org/10.1046/j.1442-200X.2002.01589.x
  109. Saltik-Temizel IN, Kocak N, Demir H. Lamivudine and high-dose interferon-alpha combination therapy for naive children with chronic hepatitis B infection. J Clin Gastroenterol 2005;39:68-70
  110. Sokucu S, Gokce S, Suoglu OD, Emiroglu H, Cevikbas U. Comparison of interferon monotherapy with interferonlamivudine combination treatment in children with chronic hepatitis B. Indian J Gastroenterol 2006;25:136-9
  111. Yilmaz A, Akcam M, Gelen T, Artan R. Lamivudine and high-dose interferon alpha 2a combination treatment in naive HBeAg-positive immunoactive chronic hepatitis B in children: an East Mediterranean center's experience. Eur J Pediatr 2007;166:195-9 https://doi.org/10.1007/s00431-006-0220-2
  112. Kansu A, Doganci T, Akman SA, Artan R, Kuyucu N, Kalayci AG, et al. Comparison of two different regimens of combined interferon-alpha2a and lamivudine therapy in children with chronic hepatitis B infection. Antivir Ther 2006;11:255-61
  113. D'Antiga L, Aw M, Atkins M, Moorat A, Vergani D, Mieli-Vergani G. Combined lamivudine/interferon-alpha treatment in 'immunotolerant' children perinatally infected with hepatitis B: a pilot study. J Pediatr 2006;148:228-33 https://doi.org/10.1016/j.jpeds.2005.09.020
  114. Lee JH, Choe BH. Optimal duration of lamivudine treatment and drug resistance in children with chronic hepatitis B. In: 55th Annual Fall Meeting of the Korean Pediatric Society; 2005; Seoul; 2005. p. 198
  115. Marcellin P, Asselah T. Resistance to adefovir: a new challenge in the treatment of chronic hepatitis B. J Hepatol 2005;43:920-3 https://doi.org/10.1016/j.jhep.2005.09.003
  116. Yeon JE, Yoo W, Hong SP, Chang YJ, Yu SK, Kim JH, et al. Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil. Gut 2006;55:1488-95 https://doi.org/10.1136/gut.2005.077099
  117. Sokal EM, Jonas MM, Kelley DA. Safety, efficacy and pharmacokinetics of adefovir dipivoxil in children and adolescents with chronic hepatitis B. In: 40th Annual meeting of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition; 2007; Barcelona, Spain; 2007. p. abstract 4
  118. Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, et al. Entecavir for treatment of lamivudinerefractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006;130:2039-49 https://doi.org/10.1053/j.gastro.2006.04.007
  119. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005;352;2682-95 https://doi.org/10.1056/NEJMoa043470