拉米夫定治疗少儿慢性乙型肝炎病毒感染的长期疗效

tonychant

Effect of long-term lamivudine in chronic hepatitis B virus-infected children. 作者：Ozgenc F, Arikan C, Sertoz RY, Nart D, Aydogdu S, Yagci RV. 杂志全名： Antiviral therapy. 年份，卷（期）: 起止页码： 2004 ;9(5):729-32 PMID： 15535410 英文摘要： OBJECTIVE: To evaluate, retrospectively, biochemical, serological and histological responses in chronic hepatitis B (C H B）--infected children who received combination therapy and continued with prolonged treatment with lamivudine (3TC). PATIENTS AND METHODS: CHB infection was defined as the presence of hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg) and hepatitis B virus (HBV) DNA in serum screened at 3-month intervals for at least 1 year, serum alanine aminotransferase (ALT) levels >1.5 times the normal limit and CHB with histological activity index (HAI) >5 by liver biopsy. A total of 99 children with CHB infection were treated with IFN-alpha (three times a week, 5 MU/m2) and 3TC (4 mg/kg/d) orally for 6 months. End of therapy response (CR) was defined as ALT normalization, HBV-DNA clearance and e seroconversion. Partial responders (PR) were defined as patients who had ALT normalization and HBV-DNA clearance, but who had not had e seroconversion. Forty-five children with PR at the end of the sixth month continued to receive 3TC alone thereafter. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. The response rate, side effects and the breakthrough infection rate were examined on prolonged 3TC treatment. Liver biopsy was held in 29 patients at median 32 (14-66) months of 3TC; pre- and post-treatment liver histology was compared. RESULTS: Pre- and post-treatment evaluation was carried out in 45 children [mean age: 11+/-4.2 years, 31 males (69%), 14 females (31%)] with PR at the end of the sixth month of combination therapy. The initial mean ALT values and HAI scores were 75.6+/-60 IU/l and 8+/-3.3, respectively. 3TC was continued for median 33 (14-66) months and CR was achieved in 15.6% (7/45) and 5.6% (2/36) at the end of first and second year, and 0% (none) at the end of third and fourth year, respectively. Breakthrough incidence was detected in six (13.3%) cases at 12 months and increased to 69.4% (n=25) and 82.4% (n=14) at the end of the second and third years, respectively. Patients with breakthrough continued to receive 3TC. Seroconversion and CR of the mutant virus was achieved in one patient (2.9%) at month 46 of treatment with 3TC. Liver biopsy was held in 29 cases at median 32 (14-66) months of 3TC. Pre- and post-treatment mean HAI scores were 8+/-3.3 and 3.9+/-2.1, respectively (P=0.000). Mean necrosing scores were not different at the beginning and end of therapy (P=1.0). Inflammation, bridging and fibrosis scores decreased to 0.8+/-0.6, 1.3+/-1.2 and 0.6+/-0.8, respectively (P=0.000, P=0.002, P=0.000). CONCLUSION: The long-term 3TC usage in children with PR does not induce complete response and is associated with high breakthrough incidence. However, histological improvement is achieved and/or sustained even in children with HBV DNA breakthrough. [摘要] 目的； 回顾性评价少儿慢性乙型肝炎感染患者接受联合治疗和继续延长拉米夫定治疗的生化，血清和组织学应答。 病人与方法； 慢性乙型肝炎感染被定义为至少1年每间隔三个月血清检测HBsAg，HBeAg与HBV DNA 阳性，ALT水平>1.5×ULN,肝活检组织学HAI>5.共有99例少儿慢性乙型肝炎感染患者接受联合α-干扰素(3次/周,5 MU/m2)和拉米夫定(4 mg/kg/d)治疗,疗程6个月.治疗完全应答(CR)定义为ALT正常,HBV DNA清除和HBeAg血清转换,部分应答(PR)定义为ALT正常,HBV DNA清除但无HBeAg血清转换.45例部分应答患者在第6个月治疗末后继续接受拉米夫定单独治疗.感染突破定义为在HBV DNA清除后血清中再次出现HBV DNA.在延长拉米夫定治疗的患者中应答率,负作用和感染突破率被检查.29例患者在拉米夫定治疗中位时间32个月(14--66个月)进行了肝活检,治疗前后肝组织学改变被比较. 结果; 对45例[平均年龄11 ±4.2岁,男性31例(69%),女性14例(31%)]在第6个月联合治疗末PR的患者治疗前后进行评价,初次ALT均数和HAI积分分别为75.6±60 IU/l 与 8±3.3,在中位时间33个月(14--66个月)的拉米夫定治疗后,第1年和第2年末分别有15.6% (7/45) 与 5.6% (2/36)的患者获得CR,在第3年和第4年末无患者获得CR,在12个月13.3%的患者发生感染突破,在第2年与第3年治疗末增长至69.4%(n=25) 和82.4% (n=14),有感染突破的患者继续接受拉米夫定治疗,在46个月拉米夫定治疗后1例(2.9%)病毒变异患者出现血清转换和CR,29例患者在拉米夫定治疗中位时间32个月(14--66个月)进行了肝活检,治疗前后平均HAI积分分别为8±3.3 和 3.9±2.1(P=0.000). 治疗开始与治疗末平均坏死积分无差异(P=1.0). 炎症,桥接与纤维化 积分分别下降到 0.8±0.6, 1.3±1.2 和 0.6±0.8(P=0.000, P=0.002, P=0.000). 结论; 在PR患儿长期使用拉米夫定治疗并不诱导产生完全应答且相关有较高的感染突破发生率, 然而,甚至在有HBV DNA 突破的患儿中也可达到和/或持续的组织学改善.

jackwen

看看