Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Therapeutic Efficacy of Lamivudine in Children and Adolescents with Chronic Hepatitis B

만성 B형 간염 소아청소년 환자에서의 라미부딘 치료 효과

  • Choi, Yujung (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Bae, Kil Seoung (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ki Hwan (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Koh, Dae Kyun (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jong-Hyun (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea)
  • 최유정 (가톨릭대학교 의과대학 소아과학교실) ;
  • 배길성 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김기환 (가톨릭대학교 의과대학 소아과학교실) ;
  • 고대균 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김종현 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2017.10.25
  • Accepted : 2017.10.31
  • Published : 2018.08.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. Methods: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. Results: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). Conclusions: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.

목적: 만성 B형 간염으로 치료가 필요하였던 소아청소년 중 lamivudine을 투여하면서 전향적으로 관찰한 자료를 검토하여 약제에 대한 치료 효과를 파악하고자 하였다. 방법: 2003년 6월 1일부터 2015년 10월 30일까지 가톨릭대학교 성빈센트병원 소아청소년과를 방문하여 만성 B형 간염의 첫 치료로 lamivudine (3 mg/kg, 최대 100 mg)을 3개월 이상 투여한 55명을 대상으로 하였다. 약제 투여 후 1개월, 3개월째, 이후는 매 3개월마다 B형 간염 바이러스(hepatitis B virus [HBV]) 표지자, HBV-DNA, 간기능을 추적하였다. 치료 중단은 alanine aminotransferase (ALT) 정상, HBeAg 음성 및 anti-HBe 양성 결과가 처음 발견된 시기로부터 12개월 후로 정하였다. 결과: 연구군은 남자가 31명(56.4%), 여자가 24명(43.6%)이었고, 약제의 첫 투여 연령은 평균 8.1세, 투여기간은 평균 23.4개월이었다. ALT 정상화는 98.2% (54/55), HBeAg 양성에서 anti-HBe 양성으로의 혈청 전환은 70.6% (36/51), HBsAg 소실은 10.9% (6/55)에서 이루어졌는데 모두 7세 미만 연령이었다. 약제 투여 6개월 시 HBV-DNA <2,000 IU/mL 바이러스 반응은 78.7% (37/47)이었고, 약제 중단 12개월 후에도 바이러스 반응이 유지되는 경우는 87.2% (34/39)이었다. Lamivudine 약제 내성이 발현된 경우는 16.4% (9/55)이었다. 결론: 만성 B형 간염을 가진 국내 소아청소년에 대한 lamivudine의 치료 효과는 유사한 외국 연구 결과에 비해 더 우수하였다. 새로 권고되고 있는 다른 항바이러스제 치료에 대한 국내에서의 지속적인 연구도 필요할 것으로 판단된다.

Keywords

References

  1. Moradpour D, Wands JR. Understanding hepatitis B virus infection. N Engl J Med 1995;332:1092-3. https://doi.org/10.1056/NEJM199504203321610
  2. World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B virus infection. Geneva: World Health Organization, 2015:10-2.
  3. Chae HB, Kim JH, Kim JK, Yim HJ. Current status of liver diseases in Korea: hepatitis B. Korean J Hepatol 2009;15 Suppl 6:S13-24. https://doi.org/10.3350/kjhep.2009.15.S6.S13
  4. Hong SG, Soh JW, Oh JH. Statistical and histological studies on HBsAg in grade-school childrens. J Korean Pediatr Soc 1979;22:433-42.
  5. Han JY, Jung TW, Koh DK, Kim JH. A survey for changed control policies of hepatitis B in the Republic of Korea. Korean J Pediatr Infect Dis 2011;18:124-34. https://doi.org/10.14776/kjpid.2011.18.2.124
  6. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2014: Korea National Health and Nutrition Examination Survey (KNHANES VI-2). Sejong: Ministry of Health and Welfare, 2015.
  7. Kim JH, Seo K, Kim HM. A comparative study for the outcome of perinatal hepatitis B prophylaxis according to the dosages of hepatitis B immunoglobulin. Seoul: Korea Centers for Disease Control and Prevention, 2006.
  8. Chang MH, Hsu HY, Hsu HC, Ni YH, Chen JS, Chen DS. The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age. Hepatology 1995;22:1387-92.
  9. Chang MH, Chen TH, Hsu HM, Wu TC, Kong MS, Liang DC, et al. Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems. Clin Cancer Res 2005;11:7953-7. https://doi.org/10.1158/1078-0432.CCR-05-1095
  10. 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
  11. 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;59:814-29. https://doi.org/10.1016/j.jhep.2013.05.016
  12. Korean Association for the Study of the Liver. 2015 Clinical practice guideline: chronic hepatitis B. Seoul: Korean Association for the Study of the Liver, 2015:123-6.
  13. 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;63:377-87. https://doi.org/10.1002/hep.28015
  14. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98. https://doi.org/10.1016/j.jhep.2017.03.021
  15. 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.
  16. Lee EH, Jang JY, Kim KM. Efficacy of lamivudine therapy for chronic hepatitis B in children. Korean J Pediatr Gastroenterol Nutr 2008;11:130-6.
  17. Koh H, Baek SY, Chung KS. Lamivudine therapy for Korean children with chronic hepatitis B. Yonsei Med J 2007;48:927-33. https://doi.org/10.3349/ymj.2007.48.6.927
  18. Jung AN, Jung HK, Choi SK, Park CO. The comparison of sequencing method with restriction fragment mass polymorphism method for the detection of HBV YMDD mutants. Korean J Clin Lab Sci 2005;37:173-7.
  19. Cheon JH, Park JW, Park KW, Kim YI, Kim SH, Lee WJ, et al. The clinical report of 1,078 cases of hepatocellular carcinomas: National Cancer Center experience. Korean J Hepatol 2004;10:288-97.
  20. Yang HI, Park EY, Kim MY. National immunization survey in South Korea, 2013. Public Health Wkly Rep 2014;7:449-54.
  21. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-39. https://doi.org/10.1002/hep.21513
  22. Hong SJ, Park HJ, Chu MA, Choi BS, Choe BH. The rate of conversion from immune-tolerant phase to early immune-clearance phase in children with chronic hepatitis B virus infection. Pediatr Gastroenterol Hepatol Nutr 2014;17:41-6. https://doi.org/10.5223/pghn.2014.17.1.41
  23. 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
  24. 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
  25. 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
  26. Moyes CD, Milne A, Waldon J. Liver function of hepatitis B carriers in childhood. Pediatr Infect Dis J 1993;12:120-5. https://doi.org/10.1097/00006454-199302000-00003
  27. Hwang SH, Kim JH, Kang JH, Hur JK, Lee KI, Oh JH, et al. Follow-up of children with chronic hepatitis B virus infection. Korean J Pediatr Infect Dis 2004;11:73-80. https://doi.org/10.14776/kjpid.2004.11.1.73
  28. Lok AS, Lai CL, Wu PC, Leung EK, Lam TS. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology 1987;92:1839-43. https://doi.org/10.1016/0016-5085(87)90613-5
  29. Yoon JH, Rhee PL, Lee HS, Kim CY. Spontaneous HBeAg clearance rate and its affecting factors inpatients with chronic hepatitis B in Korea. Korean J Gastroenterol 1992;24:1313-9.
  30. Sampliner RE. The duration of hepatitis B surface antigenemia. Arch Intern Med 1979;139:145-6. https://doi.org/10.1001/archinte.1979.03630390011007
  31. Hong SJ, Kim YH, Choe BH, Park HJ, Tak WY, Kweon YO. Current role of lamivudine regarding therapeutic response and resistance in children with chronic hepatitis B. Pediatr Gastroenterol Hepatol Nutr 2013;16:80-8. https://doi.org/10.5223/pghn.2013.16.2.80

Cited by

  1. B형 간염 예방접종 전후 연령별 B형 간염 표면항체 양성률에 대한 융합적 연구 vol.11, pp.1, 2020, https://doi.org/10.15207/jkcs.2020.11.1.077