拉米夫定对慢性乙型肝炎伴重度肝纤维化患者的长期应用疗效——NUCB 4006十年随访研究  

Long term treatment of lamivudine in chronic hepatitis B patients with severe liver fibrosis——ten-year follow-up outcomes of NUCB 4006 trial

作　　者：许蓓[1] 徐国光[2] 郭清[1] 庄焱[1] 刘芸野[1] 王晖[1] 周霞秋[1] 巫善明[2] 谢青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025 [2]上海市公共卫生临床中心

出　　处：《中华传染病杂志》2010年第11期656-661,共6页Chinese Journal of Infectious Diseases

摘　　要：目的 评估拉米夫定（LAM）对慢性乙型肝炎伴重度肝纤维化患者长期治疗的临床和组织学结果.方法 39例重度肝纤维化（Ishak评分≥4分）的慢性乙型肝炎患者接受LAM治疗,最长达10年,评估随访期末患者疾病进展、肝组织学、病毒学以及生化学应答.数据分析采用配对t检验、Fisher确切概率法以及Willcoxon检验.结果 28例完成10年随访的患者中,5例出现疾病进展,占1 7.9%.16例患者在随访期末接受了第2次肝组织活检,与基线水平相比,肝组织学活动指数和纤维化评分均有明显好转（1.1±1.4比7.1±3.2,t=-0.82,P＜0.01;3.6±2.2比5.3±0.7,t=-2.89,P＜0.05）.其中3例患者纤维比评分由基线时的5分改善为随访期末的0分.27例患者中,3例HBsAg消失,占11%,2例HBsAg血清学转换,占7%.23例HBeAg阳性患者至随访末,19例HBeAg消失,占83%,9例HBeAg血清学转换,占39%.在治疗期间,共有11例患者发生了病毒学突破或检测到LAM相关耐药变异,加用或换用其他核苷酸类似物,随访期末所有患者HBV DNA均＜1×103拷贝/mL.结论 LAM长期治疗能延缓慢性乙型肝炎伴重度肝纤维化患者的疾病进展,提高HBsAg及HBeAg的阴转率,持续维持HBV DNA于低水平,对某些患者能完全逆转肝纤维化,挽救治疗可减少LAM耐药变异对患者预后的影响.Objective To evaluate the clinical and histological outcomes in a cohort of chronic hepatitis B （CHB） patients who had histologically confirmed severe liver fibrosis and received lamivudine （LAM） therapy for up to 10 years. Methods Thirty-nine CHB patients with severe liver fibrosis （Ishak fibrosis score≥4） were treated with LAM for up to 10 years. Disease progression liver histological improvement, virological and biochemical responses were evaluated during follow-up. Data were analyzed using paired t test, Fisher exact test and Willcoxon test. Results Twenty-eight patients completed the 10-year follow-up. There were 5 （17.9% ） patients with disease progression.At the end of follow up, 16 patients received a second liver biopsy, which showed significant improvement of histological activity index （1.1 ± 1.4 vs 7. 1 ± 3.2, t =- 0.82, P〈0.01 ） and Ishak fibrosis score （3.6±2.2 vs 5.3±0.7, t= -2.89, P〈0.05） compared to baseline. There were 3 cases with Ishak fibrosis score improved from F5 to F0. Among 27 patients, 3（11% ） cases achieved hepatitis B surface antigen （HBsAg） loss and 2 （7 % ） achieved HBsAg seroconversion. At the end of follow-up, 19 out of 23 （83% ） hepatitis B e antigen （HBeAg） positive patients obtained HBeAg loss and 9 （39 % ） obtained HBeAg seroconversion. During LAM treatment, 11 patients experienced virological breakthrough or detected documented LAM-related resistance mutation. The viral loads of all patients were below 1 ×103 copy/mL at the end of follow-up after rescued by add-on or switch to another nucleotide analog.Conclusions Long-term LAM therapy can delay the disease progression in CHB patients with severe liver fibrosis, increase HBsAg and HBeAg loss rates, sustain suppression of HBV replication at a low level and even totally reverse the liver fibrosis in some patients. The effect of LAM resistance mutation on disease outcomes would be reduced by rescue therapy.

关 键 词：肝炎 乙型 慢性 肝纤维化 重度 核苷酸类似物 拉米夫定 抗药性 微生物 

分 类 号：R686[医药卫生—骨科学]