소아 만성 B형 간염 환아에서 라미부딘의 치료 효과
Efficacy of Lamivudine Therapy for Chronic Hepatitis B in Children
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Purpose: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. Methods: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. Results: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13∼58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p＞0.05). Conclusion: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.
Abstract
Purpose: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. Methods: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. Results: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13∼58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p＞0.05). Conclusion: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.
참고문헌 (27)
- Sokal EM, "ong-term lamivudine therapy for children with HBeAg-positive chronic hepatitis B", Hepatology, 43, pp.225~232 (2006)
- 최흥재, "한국인의 B형 간염 바이러스 표식자 양성율에 관한 연구", 대한소화기학회지, 15, pp.163~171 (1983)
- 백승연, "만성B형간염 환아에 대한 Interferon-alfa치료결과의 장기 추적관찰", 대한소아소화기영양학회지, 6(2), pp.140~151 (2003), 대한소아소화기영양학회
- Bortolotti F, "Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood", Gastroenterology, 99, pp.805~810 (1990)
- Honkoop P, "Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy", Hepatology, 32, pp.635~639 (2000)
- Liaw YF, "Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy", Hepatology, 30, pp.567~572 (1999)
- Sokal EM, "Interferon alpha therapy for chronic hepatitis B in children, a multinational randomized controlled trial", Gastroenterol, 114, pp.988~995 (1998)
- 고재성, "만성 B형 간염의 Interferon alpha 치료 후 혈청학적, 조직학적 소견의 변화", 대한소아소화기영양학회지, 3, pp.56~62 (2000)
- 김경모, "소아 만성 B형 간염 환자에서 Interferon alpha의 치료 효과-임상 및 조직학적 변화 소견", 소아과, 38, pp.1232~1241 (1995)
- 김홍권, "만성 B형 간염 환아에서 Interferon alpha 치료의 반응 예측 인자 분석", 소아과, 43, pp.514~519 (1999)
- 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)
- Dienstag JL, "Lamivudine as initial treatment for chronic hepatitis B in the United States", N Engl J Med, 341, pp.1256~1263 (1999)
- Schalm SW, "Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection", a randomized trial. Gut, 46, pp.562~568 (2000)
- Boni C, "Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B", J Clin Invest, 102, pp.968~975 (1998)
- Leung NW, "Extended lamivudine treatment in patients with chronic hepatitis B enhances HBe Ag seroconversion rates: results after 3 years of therapy", Hepatology, 33, pp.1527~1532 (2001)
- 박능화, "만성 B형 간질환 환자에서 라미부딘의 치료 효과 및 예측인자", 대한소화기학회지, 42(4), pp.303~312 (2003), 대한소화기학회
- Jonas MM, "Clinical trial of lamivudine in children with chronic hepatitis B", N Engl J Med, 346, pp.1706~1713 (2002)
- 장유철, "소아 만성 B형 간염에서 라미부딘 치료의 3년 누적 치료 반응과 장기 지속성", 대한소아소화기영양학회지, 7(2), pp.197~207 (2004), 대한소아소화기영양학회
- Koh H, "Lamivudine therapy for Korean children with chronic hepatitis B", Yonsei Med J, 48, pp.927~933 (2007)
- Jonas MM, "Long term lamivudine treatment of children with chronic hepatitis B: durability of therapeutic responses and safety", J Viral Hepatitis, 15, pp.20~27 (2008)
- Hom X, "Predictors of virologic response to lamivudine treatment in children with chronic hepatitis B infection", Pediatr Infect Dis J, 23, pp.441~445 (2004)
- Robert P Perrillo, "Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B", Hepatololgy, 361, pp.186~194 (2002)
- Chien RN, "Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B", Hepatology, 30, pp.770~774 (1999)
- Chang MH, "Chronic hepatitis virus infection in children", J Gastroenterol Hepatol, 13, pp.541~548 (1998)
- 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)
- Lok AS, "Chronic hepatitis B", Hepatology, 34, pp.1225~1241 (2001)
- Zeuzem S, "Dynamics of hepatitis B virus infection in vivo", J Hepatol, 27, pp.431~436 (1997)