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Lamivudine 내성 소아 청소년 만성 B형 간염에서 Adefovir의 치료 효과

Therapeutic Efficacy of Adefovir Dipivoxil in Korean Children and Adolescents with Chronic Hepatitis B who have Developed Lamivudine Resistance

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키워드

주제분류소아과학

초록

Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3∼20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9∼49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 log10 IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 log10 copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

Abstract

Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3∼20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9∼49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 log10 IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 log10 copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

참고문헌 (27)

  1. Choe BH, "Long-term therapeutic efficacy of lamivudine compared with interferon-alpha in children with chronic hepatitis B: the younger the better", J Pediatr Gastroenterol Nutr, 44, pp.92~98 (2007)
  2. Locarnini S, "Management of antiviral resistance in patients with chronic hepatitis B", Antivir Ther, 9, pp.679~693 (2004)
  3. 이선영, "소아의 만성 B형 간염: 새로운 병리조직학적 분류와 임상 소견의 상관 분석", 대한소아소화기영양학회지, 1, pp.56~78 (1998)
  4. Hsu HC, "Pathology of chronic hepatitis B virus infection in children: with special reference to the intrahepatic expression of hepatitis B virus antigens", Hepatology, 8, pp.378~382 (1988)
  5. Bortolotti F, "Liver cirrhosis associated with chronic hepatitis B virus infection in childhood", J Pediatr, 108, pp.224~227 (1986)
  6. Hsu HC, "Childhood hepatocellular carcinoma develops exclusively in hepatitis B surface antigen carriers in three decades in Taiwan. Report of 51 cases strongly associated with rapid development of liver cirrhosis", J Hepatol, 5, pp.260~267 (1987)
  7. Chu CM, "Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels", Am J Med, 116, pp.829~834
  8. Sokal E, "Drug treatment of pediatric chronic hepatitis B", Paediatr Drugs, 4, pp.361~369 (2002)
  9. Dienstag JL, "Lamivudine as initial treatment for chronic hepatitis B in the United States", N Engl J Med, 341, pp.1256~1263 (1999)
  10. Lai CL, "A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group", N Engl J Med, 339, pp.61~68 (1998)
  11. Leung NW, "The effect of longer duration of harbouring lamivudine-resistant hepatitis B virus (YMDD mutants) on liver histology during 3 years lamivudine therapy in Chinese patients", Hepatology, 34, pp.348~ (2001)
  12. 박능화, "만성 B형 간질환 환자에서 라미부딘의 치료 효과 및 예측인자", 대한소화기학회지, 42(4), pp.303~312 (2003), 대한소화기학회
  13. Song BC, "Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea", Hepatology, 32, pp.803~806 (2000)
  14. Liaw YF, "Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group", Gastroenterology, 119, pp.172~180 (2000)
  15. Sokal EM, "Areias JA, Schwarz KB, et al. Long-term lamivudine therapy for children with HBeAg-positive chronic hepatitis B", Hepatology, 43, pp.225~232 (2006)
  16. Allen MI, "Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group", Hepatology, 27, pp.1670~1677 (1998)
  17. Sun J, "Clinical and virological characteristics of lamivudine resistance in chronic hepatitis B patients: a single center experience", J Med Virol, 75, pp.391~398 (2005)
  18. Ono SK, "The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance", J Clin Invest, 107, pp.449~455 (2001)
  19. Choe BH, "Optimal duration of lamivudine treatment and drug resistance in children with chronic hepatitis B", Proceeding of the 55th Annual Fall Meeting of the Korean Pediatric Society, pp.198~ (2005)
  20. Xiong X, "Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro", Hepatology, 28, pp.1669~1673 (1998)
  21. Perrillo R, "Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants", Hepatology, 32, pp.129~134 (2000)
  22. Hadziyannis SJ, "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B", N Engl J Med, 352, pp.2673~2681 (2005)
  23. Sokal EM, "Safety, efficacy and pharmacokinetics of adefovir dipivoxil in children and adolescents with chronic hepatitis B", Proceeding of 40th Annual meeting of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition; 2007 (2007)
  24. Yeon JE, "Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil", Gut, 55, pp.1488~1495 (2006)
  25. Rapti I, "Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B", Hepatology, 45, pp.307~313 (2007)
  26. 김인희, "라미부딘 내성이 발생한 만성 B형간염에서 아데포비어에 대한 초기 치료 반응이 아데포비어 내성 발생에 미치는 영향", 대한간학회지, 13(3), pp.349~362 (2007), 대한간학회
  27. Choe BH, "Lamivudine treatment in children with chronic hepatitis B: long-term therapeutic response, optimal duration and resistance", Proceeding of the 39th Annual Meeting of European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2006, pp.47~ (2006)

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