DOI QR코드

DOI QR Code

Current Role of Lamivudine Regarding Therapeutic Response and Resistance in Children with Chronic Hepatitis B

  • Hong, Suk Jin (Department of Pediatrics, Kyungpook National University School of Medicine) ;
  • Kim, Yeo Hyang (Department of Pediatrics, Kyungpook National University School of Medicine) ;
  • Choe, Byung-Ho (Department of Pediatrics, Kyungpook National University School of Medicine) ;
  • Park, Hyo Jung (Department of Pediatrics, Kyungpook National University School of Medicine) ;
  • Tak, Won-Young (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Kweon, Young-Oh (Department of Internal Medicine, Kyungpook National University School of Medicine)
  • Received : 2013.03.18
  • Accepted : 2013.06.17
  • Published : 2013.06.30

Abstract

Purpose: To identify the predictive factors of long-term therapeutic response or resistance to lamivudine treatment in children and adolescents with chronic hepatitis B. Methods: Eighty one children and adolescents with chronic hepatitis B were included, who received lamivudine treatment for at least 6 months. Their condition was monitored for at least 12 months (12-88 months) thereafter. Twenty one (25.9%) were preschool children ($age{\leq}6$). For patients who had developed HBeAg seroconversion or breakthrough, univariate and multivariate analyses were used to identify the effects of age, gender, pretreatment alanine aminotransferase (ALT) and hepatitis B virus DNA levels. Results: HBeAg seroconversion occurred in 49 (60.5%) of the 81 patients after the initiation of the lamivudine therapy. In 65 patients whom were monitored for over 24 months, the seroconversion rate was significantly higher in younger patients (p=0.040), especially in those patients of preschool age ($age{\leq}6$, p=0.031). The seroconversion rate was significantly higher in higher pretreatment ALT (p=0.003). The breakthrough occurred in 21 (25.9%) of the 81. The breakthrough rate was lower in younger aged patients ($age{\leq}6$), and with higher pretreatment ALT levels, but no significant difference. Conclusion: Younger age is a good predictor of HBeAg seroconversion in children with long-term lamivudine treatment as well as high pretreatment ALT levels.

Keywords

References

  1. 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
  2. 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
  3. 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
  4. Choe BH, Lee JH, Jang YC, Jang CH, Oh KW, Kwon S, et al. Long-term therapeutic efficacy of lamivudine compared with 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. 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
  6. Liberek A, Szaflarska-Poplawska A, Korzon M, Luczak G, Gora-Gebka M, Los-Rycharska E, et al. Lamivudine therapy for children with chronic hepatitis B. World J Gastroenterol 2006;12:2412-6. https://doi.org/10.3748/wjg.v12.i15.2412
  7. Park NH, Shin JW, Park JH, Bang SJ, Kim DY, Joo KR, et al. Predictive factors and efficacy of lamivudine treatment in chronic hepatitis B infection. Korean J Gastroenterol 2003;42:303-12.
  8. Leung NW, Lai CL, Chang TT, Guan R, Lee CM, Ng KY, et al; Asia Hepatitis Lamivudine Study Group. 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
  9. Yoon SK, Jang JW, Kim CW, Bae SH, Choi JY, Choi SW, et al. Long-term results of lamivudine monotherapy in Korean patients with HBeAg-positive chronic hepatitis B: response and relapse rates, and factors related to durability of HBeAg seroconversion. Intervirology 2005;48:341-9. https://doi.org/10.1159/000086061
  10. 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
  11. 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
  12. Jonas MM, Mizerski J, Badia IB, Areias JA, Schwarz KB, Little NR, et al; International Pediatric Lamivudine Investigator Group. Clinical trial of lamivudine in children with chronic hepatitis B. N Engl J Med 2002;346:1706-13. https://doi.org/10.1056/NEJMoa012452
  13. 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
  14. 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
  15. 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
  16. Hong SP, Han KH, Ahn SH, Paik YH, Moon BS, Chon CY, et al. Long-term efficacy and durability of lamivudine therapy in patients with chronic hepatitis B. Korean J Hepatol 2001;7:423-31.
  17. 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
  18. Kim JM, Choe BH, Chu MA, Cho SM. Comparison of lamivudine-induced HBsAg loss rate according to age in children with chronic hepatitis B. Korean J Hepatol 2009;15:168-78. https://doi.org/10.3350/kjhep.2009.15.2.168
  19. Figlerowicz M, Kowala-Piaskowska A, Filipowicz M, Bujnowska A, Mozer-Lisewska I, Słuzewski 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
  20. 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
  21. 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
  22. 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.
  23. 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. the 39th Annual Meeting of ESPGHAN; 2006; Dresden, Germany. J Pediatr Gastroenterol Nutr 2006:E64-5.
  24. Hong SJ, Choe BH. Strategy to overcome drug resistance that develops during treatment of chronic hepatitis b in children. Pediatr Gastroenterol Hepatol Nutr 2012;15:63-73. https://doi.org/10.5223/pghn.2012.15.2.63
  25. 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;55:648-52. https://doi.org/10.1097/MPG.0b013e318262a737

Cited by

  1. A disappearing vertical infection: will hepatitis B be a forgotten disease in children? vol.29, pp.3, 2014, https://doi.org/10.3904/kjim.2014.29.3.296
  2. Lamivudine resistance in children with chronic hepatitis B vol.7, pp.6, 2013, https://doi.org/10.4254/wjh.v7.i6.896
  3. Antiviral Efficacy of Tenofovir Monotherapy in Children with Nucleos(t)ide-naive Chronic Hepatitis B vol.33, pp.2, 2013, https://doi.org/10.3346/jkms.2018.33.e11
  4. A Multicenter Study of the Antiviral Efficacy of Entecavir Monotherapy Compared to Lamivudine Monotherapy in Children with Nucleos(t)ide-naïve Chronic Hepatitis B vol.33, pp.8, 2013, https://doi.org/10.3346/jkms.2018.33.e63
  5. 만성 B형 간염 소아청소년 환자에서의 라미부딘 치료 효과 vol.25, pp.2, 2013, https://doi.org/10.14776/piv.2018.25.e2